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111 results on '"MORISCO, FILOMENA"'

1. Recalibrating survival prediction among patients receiving trans‐arterial chemoembolization for hepatocellular carcinoma

Author

Cucchetti, Alessandro, Giannini, Edoardo G., Mosconi, Cristina, Plaz Torres, Maria Corina, Pieri, Giulia, Farinati, Fabio, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Sacco, Rodolfo, Cabibbo, Giuseppe, Campani, Claudia, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Sansone, Vito, Zoli, Marco, Azzaroli, Francesco, Trevisani, Franco, Biselli, Maurizio, Caraceni, Paolo, Gramenzi, Annagiulia, Rampoldi, Davide, Reggidori, Nicola, Santi, Valentina, Stefanini, Benedetta, Granito, Alessandro, Muratori, Luca, Piscaglia, Fabio, Tovoli, Francesco, Magalotti, Donatella, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Renzulli, Matteo, Pelizzaro, Filippo, Penzo, Barbara, Marina Cela, Ester, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, de Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Dell'Isola, Serena, Biasini, Elisabetta, Olivani, Andrea, Inno, Alessandro, Marchetti, Fabiana, Celsa, Ciro, Grova, Mauro, Stornello, Caterina, Busacca, Anita, Cammà, Calogero, Maria Rizzo, Giacomo Emanuele, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Napoli, Lucia, Bevilacqua, Vittoria, Berardinelli, Dante, Borghi, Alberto, Gardini, Andrea Casadei, Conti, Fabio, Dall'Aglio, Anna Chiara, Ercolani, Giorgio, Marra, Fabio, Di Bonaventura, Chiara, Gitto, Stefano, Adotti, Valentina, Coccoli, Pietro, Malerba, Antonio, Capasso, Mario, Morisco, Filomena, Oliveri, Filippo, Romagnoli, Veronica, Cucchetti, Alessandro, Giannini, Edoardo G., Mosconi, Cristina, Plaz Torres, Maria Corina, Pieri, Giulia, Farinati, Fabio, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Sacco, Rodolfo, Cabibbo, Giuseppe, Campani, Claudia, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Sansone, Vito, Zoli, Marco, Azzaroli, Francesco, Trevisani, Franco, Biselli, Maurizio, Caraceni, Paolo, Gramenzi, Annagiulia, Rampoldi, Davide, Reggidori, Nicola, Santi, Valentina, Stefanini, Benedetta, Granito, Alessandro, Muratori, Luca, Piscaglia, Fabio, Tovoli, Francesco, Magalotti, Donatella, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Renzulli, Matteo, Pelizzaro, Filippo, Penzo, Barbara, Marina Cela, Ester, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, de Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Dell'Isola, Serena, Biasini, Elisabetta, Olivani, Andrea, Inno, Alessandro, Marchetti, Fabiana, Celsa, Ciro, Grova, Mauro, Stornello, Caterina, Busacca, Anita, Cammà, Calogero, Maria Rizzo, Giacomo Emanuele, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Napoli, Lucia, Bevilacqua, Vittoria, Berardinelli, Dante, Borghi, Alberto, Gardini, Andrea Casadei, Conti, Fabio, Dall'Aglio, Anna Chiara, Ercolani, Giorgio, Marra, Fabio, Di Bonaventura, Chiara, Gitto, Stefano, Adotti, Valentina, Coccoli, Pietro, Malerba, Antonio, Capasso, Mario, Morisco, Filomena, Oliveri, Filippo, and Romagnoli, Veronica

Subjects
Liver Cancer, Pre-TACE-Predict model, medicine.medical_specialty, business.industry, Trans-arterial chemoembolization, Pharmaceutical Science, hepatocellular carcinoma, medicine.disease, Gastroenterology, Complementary and alternative medicine, Internal medicine, Hepatocellular carcinoma, medicine, Pharmacology (medical), Trans arterial chemoembolization, business
Abstract

Background & Aims The Pre-TACE-Predict model was devised to assess prognosis of patients treated with trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). However, before entering clinical practice, a model should demonstrate that it performs a useful role. Methods We performed an independent external validation of the Pre-TACE model in a cohort that differs in setting and time period from the one that generated the original model. Data from 826 patients treated with TACE for naïve HCC (2008-2018) were used to assess calibration and discrimination of the Pre-TACE-Predict model. Results The four risk-categories identified by the Pre-TACE-Predict model had gradient monotonicity, with median survivals of 52.0, 36.2, 29.9, and 14.1 months respectively. However, predicted survivals systematically underestimated observed survivals (R2: 0.667). A recalibration was adopted maintaining fixed the prognostic index and modifying the baseline survival function. This resulted in an almost perfect calibration (R2: 0.995) in all the four risk categories. Cox regressions showed that aetiology and macrovascular invasion, included in the Pre-TACE-Predict model, had no prognostic impact in the present study population, and that coefficients for tumour size and multiplicity were overestimated. The c-index was similar to that of the m-HAP-III, but higher than those of HAP, m-HAP-II and the six-and-twelve models. Conclusions The recalibration of Pre-TACE-Predict model improved the estimation of survival probabilities of HCC patients treated with TACE. The highest discriminatory ability of the Pre-TACE-model in comparison to other available models, together with risk stratification and recalibration, makes it the best prognostic tool currently available for these patients.

Published
2021
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2. Monofocal hepatocellular carcinoma: How much does size matter?

Author

Pelizzaro, Filippo, Penzo, Barbara, Peserico, Giulia, Imondi, Angela, Sartori, Anna, Vitale, Alessandro, Cillo, Umberto, Giannini, Edoardo G., Forgione, Antonella, Ludovico Rapaccini, Gian, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Giuseppe Foschi, Francesco, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Oliveri, Filippo, Trevisani, Franco, Farinati, Fabio, Biselli, Maurizio, Caraceni, Paolo, Garuti, Francesca, Gramenzi, Annagiulia, Neri, Andrea, Santi, Valentina, Granito, Alessandro, Muratori, Luca, Piscaglia, Fabio, Sansone, Vito, Tovoli, Francesco, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Sammarco, Ambra, Cela, Ester Marina, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, Moscatelli, Alessandro, Pellegatta, Gaia, de Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Missale, Gabriele, Inno, Alessandro, Marchetti, Fabiana, Busacca, Anita, Cammà, Calogero, Martino, Vincenzo Di, Emanuele Maria Rizzo, Giacomo, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Bevilacqua, Vittoria, Borghi, Alberto, Casadei Gardini, Andrea, Conti, Fabio, Dall'Aglio, Anna Chiara, Ercolani, Giorgio, Mirici, Federica, Campani, Claudia, Bonaventura, Chiara Di, Gitto, Stefano, Coccoli, Pietro, Malerba, Antonio, Guarino, Maria, Brunetto, Maurizia, Romagnoli, Veronica, Pelizzaro, Filippo, Penzo, Barbara, Peserico, Giulia, Imondi, Angela, Sartori, Anna, Vitale, Alessandro, Cillo, Umberto, Giannini, Edoardo G., Forgione, Antonella, Ludovico Rapaccini, Gian, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Giuseppe Foschi, Francesco, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Oliveri, Filippo, Trevisani, Franco, Farinati, Fabio, Biselli, Maurizio, Caraceni, Paolo, Garuti, Francesca, Gramenzi, Annagiulia, Neri, Andrea, Santi, Valentina, Granito, Alessandro, Muratori, Luca, Piscaglia, Fabio, Sansone, Vito, Tovoli, Francesco, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Sammarco, Ambra, Cela, Ester Marina, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, Moscatelli, Alessandro, Pellegatta, Gaia, de Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Missale, Gabriele, Inno, Alessandro, Marchetti, Fabiana, Busacca, Anita, Cammà, Calogero, Martino, Vincenzo Di, Emanuele Maria Rizzo, Giacomo, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Bevilacqua, Vittoria, Borghi, Alberto, Casadei Gardini, Andrea, Conti, Fabio, Dall'Aglio, Anna Chiara, Ercolani, Giorgio, Mirici, Federica, Campani, Claudia, Bonaventura, Chiara Di, Gitto, Stefano, Coccoli, Pietro, Malerba, Antonio, Guarino, Maria, Brunetto, Maurizia, Romagnoli, Veronica, Giannini, Edoardo G, Svegliati-Baroni, Gianluca, for the Italica, Group, Pelizzaro F., Penzo B., Peserico G., Imondi A., Sartori A., Vitale A., Cillo U., Giannini E.G., Forgione A., Ludovico Rapaccini G., Di Marco M., Caturelli E., Zoli M., Sacco R., Cabibbo G., Marra F., Mega A., Morisco F., Gasbarrini A., Svegliati-Baroni G., Giuseppe Foschi F., Olivani A., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Oliveri F., Trevisani F., Farinati F., Biselli M., Caraceni P., Garuti F., Gramenzi A., Neri A., Santi V., Granito A., Muratori L., Piscaglia F., Sansone V., Tovoli F., Dajti E., Marasco G., Ravaioli F., Cappelli A., Golfieri R., Mosconi C., Renzulli M., Sammarco A., Cela E.M., Facciorusso A., Cacciato V., Casagrande E., Moscatelli A., Pellegatta G., de Matthaeis N., Allegrini G., Lauria V., Ghittoni G., Pelecca G., Chegai F., Coratella F., Ortenzi M., Missale G., Inno A., Marchetti F., Busacca A., Qabibboz G., Camma C., Martino V.D., Emanuele Maria Rizzo G., Franze M.S., Saitta C., Sauchella A., Bevilacqua V., Borghi A., Casadei Gardini A., Conti F., Dall'Aglio A.C., Ercolani G., Mirici F., Campani C., Bonaventura C.D., Gitto S., Coccoli P., Malerba A., Guarino M., Brunetto M., Romagnoli V., Rapaccini, Gian Ludovico, and Foschi, Francesco Giuseppe

Subjects
medicine.medical_specialty, Multivariate analysis, Carcinoma, Hepatocellular, Independent predictor, Gastroenterology, Resection, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Overall survival, Hepatectomy, Humans, Staging system, Neoplasm Staging, Retrospective Studies, Settore MED/12 - Gastroenterologia, Hepatology, treatment, business.industry, Settore MED/09 - MEDICINA INTERNA, Liver Neoplasms, bclc staging system, monofocal hepatocellular carcinoma, medicine.disease, digestive system diseases, Survival benefit, Italy, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, liver resection, prognosis, 030211 gastroenterology & hepatology, business, Liver cancer, prognosi
Abstract

Background & Aims: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5cm) monofocal (HCC). Methods: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5cm; SEM-HCC), 163 patients with larger tumours (>5cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). Results: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0months; P&nbsp

Published
2021

3. Effect of direct-acting antivirals on future occurrence of hepatocellular carcinoma in compensated cirrhotic patients

Author

Cucchetti, Alessandro, D’Amico, Gennaro, Trevisani, Franco, Morelli, Maria Cristina, Vitale, Alessandro, Pinna, Antonio Daniele, Cescon, Matteo, Cillo, Umberto, Burra, Patrizia, Russo, Francesco P., Mescoli, Claudia, Rendina, Maria, Lupo, Luigi G., Losito, Francesco, Fucilli, Fabio, Brancaccio, Giusep-Pina, Persico, Marcello, Viganò, Luca, Iavarone, Massimo, D’Ambrosio, Roberta, Sangiovanni, Angelo, Renzulli, Matteo, Galati, Giovanni, Ponziani, Francesca Romana, Pompili, Maurizio, Miele, Luca, Grieco, Antonio, Rapaccini, Gianlodovico, Gasbarrini, Antonio, Sandri, Giovanni Battisa Levi, Lai, Quirino, Melandro, Fabio, Rossi, Massimo, Lenci, Ilaria, Manzia, Tommaso Maria, Tortora, Raffaella, Di Costanzo, Giovan Giuseppe, Sacco, Rodolfo, Simonetti, Natalia, Morisco, Filomena, Guarino, Maria, Cabibbo, Giuseppe, Bhoori, Carlo Sposito Sherrie, Di Sandro, Stefano, Foschi, Francesco Giuseppe, Gardini, Andrea Casadei, Nicolini, Daniele, Mazzocato, Susanna, Alba, Kostandini, Violi, Paola, Baccarani, Umberto, Pravisani, Riccardo, A. Cucchetti, G. D'Amico, F. Trevisani, M.C. Morelli, A. Vitale, A.D.Pinna, M. Cescon, Cucchetti, Alessandro, D’Amico, Gennaro, Trevisani, Franco, Morelli, Maria Cristina, Vitale, Alessandro, Pinna, Antonio Daniele, Cescon, Matteo, Cillo, Umberto, Burra, Patrizia, Russo, Francesco P., Mescoli, Claudia, Rendina, Maria, Lupo, Luigi G., Losito, Francesco, Fucilli, Fabio, Brancaccio, Giusep-Pina, Persico, Marcello, Viganò, Luca, Iavarone, Massimo, D’Ambrosio, Roberta, Sangiovanni, Angelo, Renzulli, Matteo, Galati, Giovanni, Ponziani, Francesca Romana, Pompili, Maurizio, Miele, Luca, Grieco, Antonio, Rapaccini, Gianlodovico, Gasbarrini, Antonio, Sandri, Giovanni Battisa Levi, Lai, Quirino, Melandro, Fabio, Rossi, Massimo, Lenci, Ilaria, Manzia, Tommaso Maria, Tortora, Raffaella, Di Costanzo, Giovan Giuseppe, Sacco, Rodolfo, Simonetti, Natalia, Morisco, Filomena, Guarino, Maria, Cabibbo, Giuseppe, Bhoori, Carlo Sposito Sherrie, Di Sandro, Stefano, Foschi, Francesco Giuseppe, Gardini, Andrea Casadei, Nicolini, Daniele, Mazzocato, Susanna, Alba, Kostandini, Violi, Paola, Baccarani, Umberto, and Pravisani, Riccardo

Subjects
Male, Time Factors, Sustained Virologic Response, Hepatocellular carcinoma, Hepacivirus, Direct-acting antiviral, Direct-acting antivirals, medicine.disease_cause, Gastroenterology, Competing risk, Hepatitis C, Markov model, Survival benefit, Sustained virological response, Hepatology, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, biology, Incidence, Incidence (epidemiology), Liver Neoplasms, Middle Aged, Markov Chains, Competing risk Direct-acting antivirals Hepatitis C Hepatocellular carcinoma Markov model Survival benefit Sustained virological response, Italy, Liver Neoplasm, Female, 030211 gastroenterology & hepatology, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Time Factor, Hepatitis C virus, Antiviral Agents, 03 medical and health sciences, Internal medicine, medicine, Humans, Antiviral Agent, Hepaciviru, business.industry, Risk Factor, Carcinoma, Hepatocellular, Markov Chain, medicine.disease, biology.organism_classification, digestive system diseases, Settore MED/18 - Chirurgia Generale, Liver function, Varices, business
Abstract

Background: The achievement of high rates of sustained virological response (SVR) with direct-acting antivirals (DAAs) in hepatitis C virus (HCV) infected patients will reduce decompensating terminal events. Aims: To investigate whether hepatocellular carcinoma (HCC) occurrence could change due to the DAA-induced increase in life-expectancy. Methods: A Markov model was built on clinical data of 494 cirrhotic patients and available literature to estimate probabilities of “death before HCC” and of “HCC occurrence” without and with DAA. Results: In comparison to untreated patients, DAA therapy reduced the 20-year mortality before HCC by 21.9% in patients without varices and by 21.5% in those with varices, considering an SVR of 95% and no direct effect on hepatocarcinogenesis. Tumour occurrence increased by 5%–8.2% and the proportion of HCCs diagnosed in compensated stages increased to >98%. If we consider DAA as having “anti-tumoral” effects, the benefit becomes greater, achieving a 20-year survival of 81.5% in patients without varices, and 52.2% in patients with varices. Instead, if we consider DAA as having a “pro-tumoral” effect, then, the increased incidence of HCC nullifies the survival benefits. Conclusion: DAAs drastically reduce the mortality caused by the liver function worsening, increasing the proportion of HCCs diagnosed in compensated stages. Knowledge of the DAA effect on hepatocarcinogenesis remains pivotal. © 2017 Editrice Gastroenterologica Italiana S.r.l.

Published
2018
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4. HepaDisk – A new quality of life questionnaire for HCV patients

Author

Fagiuoli, Stefano, Caporaso, Nicola, Morisco, Filomena, Buelli, Fabio, Gualberti, Giuliana, Saragaglia, Valeria, Chessa, Luchino, Corti, Giampaolo, Maida, Ivana, Mastroianni, Claudio M., Pirisi, Mario, Russo, Francesco P., Farina, Francesca, Giannitrapani, Lydia, Toniutto, Pierluigi, Tarquini, Pierluigi, Tundo, Paolo, Vecchiet, Jacopo, Vinci, Maria, Taliani, Gloria, HepaDisk Study Group, Fagiuoli, S, Caporaso, N, Morisco, F, Buelli, F, Gualberti, G, Saragaglia, V, Chessa, L, Corti, G, Maida, I, Mastroianni, C, Pirisi, M, Russo, F, Farina, F, Giannitrapani, L, Toniutto, P, Tarquini, P, Tundo, P, Vecchiet, J, Vinci, M, Taliani, G, Fagiuoli, Stefano, Caporaso, Nicola, Morisco, Filomena, Buelli, Fabio, Gualberti, Giuliana, Saragaglia, Valeria, Chessa, Luchino, Corti, Giampaolo, Maida, Ivana, Mastroianni, Claudio M., Pirisi, Mario, Russo, Francesco P., Farina, Francesca, Giannitrapani, Lydia, Toniutto, Pierluigi, Tarquini, Pierluigi, Tundo, Paolo, Vecchiet, Jacopo, Vinci, Maria, Taliani, Gloria, and Fagiuoli S, Caporaso N, Morisco F, Buelli F, Gualberti G, Saragaglia V, Chessa L, Corti G, Maida I, Mastroianni CM, Pirisi M, Russo FP, Farina F, Giannitrapani L, Toniutto P, Tarquini P, Tundo P, Vecchiet J, Vinci M, Taliani G

Subjects
Adult, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Psychometrics, gastroenterology, Disease, Severity of Illness Index, Correlation, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Quality of life, Disease severity, Cronbach's alpha, Surveys and Questionnaires, Internal medicine, medicine, Humans, Aged, Rank correlation, Aged, 80 and over, business.industry, Burden of disease, Reproducibility of Results, psychometric validation, Middle Aged, medicine.disease, Hepatitis C, Psychometric validation, burden of disease, hcv, pro development, hepatology, Italy, 030220 oncology & carcinogenesis, HCV, PRO development, Quality of Life, Female, 030211 gastroenterology & hepatology, Observational study, business
Abstract

Background Since most patients with hepatitis C virus (HCV) infection now receive treatment irrespective of liver disease severity, special attention to patient quality of life (QoL), including psycho-social aspects, is required. No QoL questionnaire is specific for patients with HCV. Aims To develop and validate a short Italian questionnaire (HepaDisk) assessing the QoL of patients affected by HCV with intuitive graphic results that is understandable by patients and physicians. Methods A questionnaire, drafted by a steering committee, underwent a Delphi survey. A multicenter, observational study was conducted to validate the developed HepaDisk versus other tools (CLDQ-I, SF-36, WPAI:HCV), and to evaluate its correlation with disease severity in Italian patients with HCV. Results The 10-item questionnaire was validated in 214 patients. HepaDisk showed a high correlation with CLDQ overall score and WPAI:HCV activity impairment (Spearman’s rank correlation: 0.651 and 0.595, respectively) and a lower correlation with SF-36. Strong internal consistency (Cronbach coefficient: 0.912), good test–retest reliability (Pearson’s correlation coefficient: 0.789; 95% CI, 0.714–0.865), and responsiveness to changes among improved patients were demonstrated. Conclusion HepaDisk is a reliable and user-friendly tool that can monitor disease impact on patient QoL over time, providing a visual representation easily understandable by both patients and physicians.

Published
2019

5. Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: A pilot case-control study

Author

Morisco, Filomena, Camera, Silvia, Guarino, Maria, Tortora, Raffaella, Cossiga, Valentina, Vitiello, Anna, Cordone, Gabriella, Caporaso, Nicola, Di Costanzo, Giovan Giuseppe, Zoli, M., Garuti, F., Neri, A., Piscaglia, F., Lenzi, B., Valente, M., Trevisani, F., Bolondi, L., Biselli, M., Caraceni, P., Cucchetti, A., Domenicali, M., Gramenzi, A., Magalotti, D., Serra, C., Venerandi, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Giannini, E. G., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Caturelli, E., Roselli, P., Lauria, V., Pelecca, G., Dell'Isola, S., Ialungo, A. M., Rastrelli, E., Cabibbo, G., Cammà, C., Attardo, S., Rossi, M., Cavani, G., Virdone, R., Affronti, A., Nardone, G., Felder, M., Mega, A., Ciccarese, F., Del Poggio, P., Olmi, S., Foschi, F. G., Bevilacqua, V., Dall'Aglio, A. C., Ercolani, G., Fiorini, E., Casadei Gardini, A., Lanzi, A., Mirici Cappa, F., Sacco, R., Mismas, V., Svegliati Barone, G., Schiadà, L., Farinati, F., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Rapaccini, G. L., de Matthaeis, N., Gasbarrini, A., Rinninella, E., Olivani, A., Missale, G., Biasini, E., Di Marco, M., Balsamo, C., Vavassori, E., Masotto, A., Marchetti, F., Valerio, M., Marra, F., Aburas, S., Campani, C., Dragoni, G., Borzio, F., Benvegnù, L., Festi, D., Marasco, Giovanni, Ravaioli, Federico, Morisco, Filomena, Camera, Silvia, Guarino, Maria, Tortora, Raffaella, Cossiga, Valentina, Vitiello, Anna, Cordone, Gabriella, Caporaso, Nicola, Di Costanzo, Giovan Giuseppe, Zoli, M., Garuti, F., Neri, A., Piscaglia, F., Lenzi, B., Valente, M., Trevisani, F., Bolondi, L., Biselli, M., Caraceni, P., Cucchetti, A., Domenicali, M., Gramenzi, A., Magalotti, D., Serra, C., Venerandi, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Giannini, E.G., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Caturelli, E., Roselli, P., Lauria, V., Pelecca, G., Dell'Isola, S., Ialungo, A.M., Rastrelli, E., Cabibbo, G., Cammà, C., Attardo, S., Rossi, M., Cavani, G., Virdone, R., Affronti, A., Nardone, G., Felder, M., Mega, A., Ciccarese, F., Del Poggio, P., Olmi, S., Foschi, F.G., Bevilacqua, V., Dall'Aglio, A.C., Ercolani, G., Fiorini, E., Casadei Gardini, A., Lanzi, A., Mirici Cappa, F., Sacco, R., Mismas, V., Svegliati Barone, G., Schiadà, L., Farinati, F., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Rapaccini, G.L., de Matthaeis, N., Gasbarrini, A., Rinninella, E., Olivani, A., Missale, G., Biasini, E., Di Marco, M., Balsamo, C., Vavassori, E., Masotto, A., Marchetti, F., Valerio, M., Marra, F., Aburas, S., Campani, C., Dragoni, G., Borzio, F., Benvegnù, L., Festi, D., Marasco, Giovanni, Ravaioli, Federico, Giannini, E. G., Ialungo, A. M., Foschi, F. G., Dall'Aglio, A. C., Rapaccini, G. L., Garuti, Franca, Venerandi, Laura, Mega, Angela, Fiorini, Elisabetta, Lanzi, Andrea, and Balsamo, Carlo

Subjects
medicine.medical_specialty, Large HCC, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Survival rate, Laser ablation, TACE, Univariate analysis, business.industry, Standard treatment, Large HCC, Laser ablation, TACE, Oncology, Cancer, Hepatology, medicine.disease, BCLC Stage, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Liver cancer, business, Research Paper
Abstract

// Filomena Morisco 1 , Silvia Camera 1 , Maria Guarino 1 , Raffaella Tortora 2 , Valentina Cossiga 1 , Anna Vitiello 1 , Gabriella Cordone 2 , Nicola Caporaso 1 , Giovan Giuseppe Di Costanzo 2 and Italian Liver Cancer (ITA.LI.CA) group 1 Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, Italy 2 Hepatology Unit, “Cardarelli” Hospital, Naples, Italy Correspondence to: Filomena Morisco, email: filomena.morisco@unina.it Keywords: large HCC; laser ablation; TACE Received: December 13, 2017 Accepted: February 27, 2018 Published: April 03, 2018 ABSTRACT Background: Limited therapies are available for large (≥40 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods: Eighty-two patients with a single HCC nodule ≥40 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively ( p 60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively ( p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions: LA is a more effective therapeutic option than TACE in patients with solitary large HCC.

Published
2018

6. Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis

Author

Guarino, Maria, Viganò, Luca, Ponziani, Francesca Romana, Giannini, Edoardo Giovanni, Lai, Quirino, Morisco, Filomena, Vitale, Alessandro, Russo, Francesco Paolo, Cillo, Umberto, Burra, Patrizia, Mescoli, Claudia, Gambato, Martina, Sessa, Anna, Cabibbo, Giuseppe, Viganò, Mauro, Galati, Giovanni, Villa, Erica, Iavarone, Massimo, Brancaccio, Giuseppina, Rendina, Maria, Lupo, Luigi G., Losito, Francesco, Fucilli, Fabio, Persico, Marcello, D'Ambrosio, Roberta, Sangiovanni, Angelo, Cucchetti, Alessandro, Trevisani, Franco, Matteo, Renzulli, Miele, Luca, Grieco, Antonio, Lodovico Rapaccini, Gian, Pompili, Maurizio, Gasbarrini, Antonio, Battisa Levi Sandri, Giovanni, Melandro, Fabio, Rossi, Massimo, Lenci, Ilaria, Manzia, Tommaso Maria, Tortora, Raffaella, Di Costanzo, Giovan Giuseppe, Sacco, Rodolfo, Ghinolfi, Davide, Rreka, Erion, Carrai, Paola, Simonetti, Natalia, Sposito, Carlo, Bhoori, Sherrie, di Sandro, Stefano, Foschi, Francesco Giuseppe, Casadei Gardini, Andrea, Nicolini, Daniele, Mazzocato, Susanna, Kostandini, Alba, Violi, Paola, Baccarani, Umberto, Pravisani, Riccardo, Vincenzi, Valter, ROSA MARIA, Guarino, Luca, Viganò, Francesca Romana, Ponziani, Edoardo Giovanni, Giannini, Quirino, Lai, Filomena, Morisco, Alessandro, Vitale, Russo, Francesco Paolo, Umberto, Cillo, Patrizia, Burra, Claudia, Mescoli, Martina, Gambato, Anna, Sessa, Cabibbo, Giuseppe, Viganò, Mauro, Galati, Giovanni, Erica, Villa, Iavarone, Massimo, Brancaccio, Giuseppina, Maria, Rendina, Luigi G., Lupo, Francesco, Losito, Fabio, Fucilli, Marcello, Persico, Roberta, D'Ambrosio, Angelo, Sangiovanni, Alessandro, Cucchetti, Franco, Trevisani e Matteo Renzulli, Luca, Miele, Antonio, Grieco, Gian, Lodovico Rapaccini, Maurizio, Pompili, Antonio, Gasbarrini, Giovanni, Battisa Levi Sandri, Fabio, Melandro, Massimo, Rossi, Ilaria, Lenci, Tommaso, Maria Manzia, Raffaella, Tortora, Giovan Giuseppe, Di Costanzo, Sacco, Rodolfo, Davide, Ghinolfi, Erion, Rreka, Paola, Carrai, Natalia, Simonetti, Carlo, Sposito, Sherrie, Bhoori, Stefano, di Sandro, Francesco Giuseppe, Foschi, Andrea, Casadei Gardini, Daniele, Nicolini, Susanna, Mazzocato, Kostandini, Alba, Paola, Violi, Umberto, Baccarani, Riccardo, Pravisani, Valter, Vincenzi, Guarino, Maria, Viganò, Luca, Ponziani, Francesca Romana, Giannini, Edoardo Giovanni, Lai, Quirino, Morisco, Filomena, Vitale, Alessandro, Cillo, Umberto, Burra, Patrizia, Mescoli, Claudia, Gambato, Martina, Sessa, Anna, Villa, Erica, Rendina, Maria, Lupo, Luigi G., Losito, Francesco, Fucilli, Fabio, Persico, Marcello, D'Ambrosio, Roberta, Sangiovanni, Angelo, Cucchetti, Alessandro, Trevisani e Matteo Renzulli, Franco, Miele, Luca, Grieco, Antonio, Lodovico Rapaccini, Gian, Pompili, Maurizio, Gasbarrini, Antonio, Battisa Levi Sandri, Giovanni, Melandro, Fabio, Rossi, Massimo, Lenci, Ilaria, Manzia, Tommaso Maria, Tortora, Raffaella, Di Costanzo, Giovan Giuseppe, Ghinolfi, Davide, Rreka, Erion, Carrai, Paola, Simonetti, Natalia, Sposito, Carlo, Bhoori, Sherrie, di Sandro, Stefano, Foschi, Francesco Giuseppe, Casadei Gardini, Andrea, Nicolini, Daniele, Mazzocato, Susanna, Violi, Paola, Baccarani, Umberto, Pravisani, Riccardo, Vincenzi, Valter, CASADEI GARDINI, Andrea, Trevisani, Franco, and Matteo, Renzulli

Subjects
Oncology, Liver Cirrhosis, Cirrhosis, Sustained Virologic Response, DAA, HCC, HCV, Recurrence, medicine.disease_cause, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Antiviral Agents, Carcinoma, Hepatocellular, Disease Progression, Hepatitis C, Chronic, Humans, Liver Neoplasms, Neoplasm Recurrence, Local, Neoplasm Staging, Risk Assessment, Chronic, Gastroenterology, hepatocellular carcinoma, Hepatitis C, Local, Hepatology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Risk assessment, Direct acting, Risk analysis, medicine.medical_specialty, Hepatitis C virus, DAA, HCC, HCV, Recurrence, 03 medical and health sciences, Internal medicine, medicine, Antiviral treatment, business.industry, Carcinoma, Hepatocellular, medicine.disease, Settore MED/18 - Chirurgia Generale, Neoplasm Recurrence, business
Abstract

Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies. The suggested aggressive pattern (rapid growth and vascular invasion) of tumor recurrence after DAAs still remains to be confirmed. Several limitations of the available studies were highlighted, and should drive future researches. The time-to-recurrence should be computed since the last HCC treatment and results stratified for cirrhosis and sustained viral response. Any comparison with historical series is of limited interest because of a number of biases affecting these studies and differences between enrolled patients. Prospective intention-to-treat analyses will be probably the best contribution to drive clinical practice, provided that a randomized trial can be difficult to design.

Published
2018

7. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial

Author

Caraceni, Paolo, Riggio, Oliviero, Angeli, Paolo, Alessandria, Carlo, Neri, Sergio, Foschi, Francesco G, Levantesi, Fabio, Airoldi, Aldo, Boccia, Sergio, Svegliati-Baroni, Gianluca, Fagiuoli, Stefano, Romanelli, Roberto G, Cozzolongo, Raffaele, Di Marco, Vito, Sangiovanni, Vincenzo, Morisco, Filomena, Toniutto, Pierluigi, Tortora, Annalisa, De Marco, Rosanna, Angelico, Mario, Cacciola, Irene, Elia, Gianfranco, Federico, Alessandro, Massironi, Sara, Guarisco, Riccardo, Galioto, Alessandra, Ballardini, Giorgio, Rendina, Maria, Nardelli, Silvia, Piano, Salvatore, Elia, Chiara, Prestianni, Loredana, Cappa, Federica Mirici, Cesarini, Lucia, Simone, Loredana, Pasquale, Chiara, Cavallin, Marta, Andrealli, Alida, Fidone, Federica, Ruggeri, Matteo, Roncadori, Andrea, Baldassarre, Maurizio, Tufoni, Manuel, Zaccherini, Giacomo, Bernardi, Mauro, Domenicali, Marco, Giannone, Ferdinando A, Merli, Manuela, Gioia, Stefania, Fasolato, Silvano, Sticca, Antonietta, Campion, Daniela, Risso, Alessandro, Saracco, Giorgio M, Maiorca, Daniela, Rizzotto, Agostino, Lanzi, Arianna, Neri, Elga, Visani, Anna, Mastroianni, Antonio, Alberti, Alberto B, Mazzarelli, Chiara, Vangeli, Marcello, Marzioni, Marco, Capretti, Francesca, Kostandini, Alba, Magini, Giulia, Colpani, Maria, Laffi, Giacomo, Gabbani, Tommaso, Marsico, Maria, Zappimbulso, Marianna, Petruzzi, Josè, Calvaruso, Vincenza, Parrella, Giovanni, Caporaso, Nicola, Auriemma, Francesco, Guarino, Maria, Pugliese, Fabio, Gasbarrini, Antonio, Leo, Pietro, De Leonardis, Francesco, Pecchioli, Alessandra, Rossi, Piera, Raimondo, Giovanni, Negri, Elisa, Dallio, Marcello, Loguercio, Carmelina, Conte, Dario, Celli, Natascia, Bringiotti, Roberto, Castellaneta, Nicola M, Salerno, Francesco, ANSWER Study Investigators, Caraceni, Paolo, Riggio, Oliviero, Angeli, Paolo, Alessandria, Carlo, Neri, Sergio, Foschi, Francesco G, Levantesi, Fabio, Airoldi, Aldo, Boccia, Sergio, Svegliati-Baroni, Gianluca, Fagiuoli, Stefano, Romanelli, Roberto G, Cozzolongo, Raffaele, Di Marco, Vito, Sangiovanni, Vincenzo, Morisco, Filomena, Toniutto, Pierluigi, Tortora, Annalisa, De Marco, Rosanna, Angelico, Mario, Cacciola, Irene, Elia, Gianfranco, Federico, Alessandro, Massironi, Sara, Guarisco, Riccardo, Galioto, Alessandra, Ballardini, Giorgio, Rendina, Maria, Nardelli, Silvia, Piano, Salvatore, Elia, Chiara, Prestianni, Loredana, Cappa, Federica Mirici, Cesarini, Lucia, Simone, Loredana, Pasquale, Chiara, Cavallin, Marta, Andrealli, Alida, Fidone, Federica, Ruggeri, Matteo, Roncadori, Andrea, Baldassarre, Maurizio, Tufoni, Manuel, Zaccherini, Giacomo, Bernardi, Mauro, Domenicali, Marco, Giannone, Ferdinando A, Merli, Manuela, Gioia, Stefania, Fasolato, Silvano, Sticca, Antonietta, Campion, Daniela, Risso, Alessandro, Saracco, Giorgio M, Maiorca, Daniela, Rizzotto, Agostino, Lanzi, Arianna, Neri, Elga, Visani, Anna, Mastroianni, Antonio, Alberti, Alberto B, Mazzarelli, Chiara, Vangeli, Marcello, Marzioni, Marco, Capretti, Francesca, Kostandini, Alba, Magini, Giulia, Colpani, Maria, Laffi, Giacomo, Gabbani, Tommaso, Marsico, Maria, Zappimbulso, Marianna, Petruzzi, Josè, Calvaruso, Vincenza, Parrella, Giovanni, Caporaso, Nicola, Auriemma, Francesco, Guarino, Maria, Pugliese, Fabio, Gasbarrini, Antonio, Leo, Pietro, De Leonardis, Francesco, Pecchioli, Alessandra, Rossi, Piera, Raimondo, Giovanni, Negri, Elisa, Dallio, Marcello, Loguercio, Carmelina, Conte, Dario, Celli, Natascia, Bringiotti, Roberto, Castellaneta, Nicola M, Salerno, Francesco, Caraceni P1, Riggio O2, Angeli P3, Alessandria C4, Neri S5, Foschi FG6, Levantesi F7, Airoldi A8, Boccia S9, Svegliati-Baroni G10, Fagiuoli S11, Romanelli RG12, Cozzolongo R13, Di Marco Vito, Sangiovanni V15, Morisco F16, Toniutto P17, Tortora A18, De Marco R19, Angelico M20, Cacciola I21, Elia G22, Federico A23, Massironi S24, Guarisco R25, Galioto A26, Ballardini G27, Rendina M28, Nardelli S2, Piano S3, Elia C4, Prestianni L5, Cappa FM6, Cesarini L8, Simone L9, Pasquale C2, Cavallin M3, Andrealli A4, Fidone F5, Ruggeri M29, Roncadori A30, Baldassarre M1, Tufoni M1, Zaccherini G1, Bernardi M31, Domenicali M, Giannone FA, Merli M, Gioia S, Fasolato S, Sticca A, Campion D, Risso A, Saracco GM, Maiorca D, Rizzotto A, Lanzi A, Neri E, Visani A, Mastroianni A, Alberti AB, Mazzarelli C, Vangeli M, Marzioni M, Capretti F, Kostandini A, Magini G, Colpani M, Laffi G, Gabbani T, Marsico M, Zappimbulso M, Petruzzi J, Calvaruso Vincenza, Parrella G, Caporaso N, Auriemma F, Guarino M, Pugliese F, Gasbarrini A, Leo P, De Leonardis F, Pecchioli A, Rossi P, Raimondo G, Negri E, Dallio M, Loguercio C, Conte D, Celli N, Bringiotti R, Castellaneta NM, Salerno F., Caraceni P, Riggio O, Angeli P, Alessandria C, Neri S, Foschi FG, Levantesi F, Airoldi A, Boccia S, Svegliati-Baroni G, Fagiuoli S, Romanelli RG, Cozzolongo R, Di Marco V, Sangiovanni V, Morisco F, Toniutto P, Tortora A, De Marco R, Angelico M, Cacciola I, Elia G, Federico A, Massironi S, Guarisco R, Galioto A, Ballardini G, Rendina M, Nardelli S, Piano S, Elia C, Prestianni L, Cappa FM, Cesarini L, Simone L, Pasquale C, Cavallin M, Andrealli A, Fidone F, Ruggeri M, Roncadori A, Baldassarre M, Tufoni M, Zaccherini G, Bernardi M, Domenicali M, Giannone FA, Merli M, Gioia S, Fasolato S, Sticca A, Campion D, Risso A, Saracco GM, Maiorca D, Rizzotto A, Lanzi A, Neri E, Visani A, Mastroianni A, Alberti AB, Mazzarelli C, Vangeli M, Marzioni M, Capretti F, Kostandini A, Magini G, Colpani M, Laffi G, Gabbani T, Marsico M, Zappimbulso M, Petruzzi J, Calvaruso V, Parrella G, Caporaso N, Auriemma F, Guarino M, Pugliese F, Gasbarrini A, Leo P, De Leonardis F, Pecchioli A, Rossi P, Raimondo G, Negri E, Dallio M, Loguercio C, Conte D, Celli N, Bringiotti R, Castellaneta NM, Salerno F., Caraceni, P, Riggio, O, Angeli, P, Alessandria, C, Neri, S, Foschi, F, Levantesi, F, Airoldi, A, Boccia, S, Svegliati-Baroni, G, Fagiuoli, S, Romanelli, R, Cozzolongo, R, Di Marco, V, Sangiovanni, V, Morisco, F, Toniutto, P, Tortora, A, De Marco, R, Angelico, M, Cacciola, I, Elia, G, Federico, A, Massironi, S, Guarisco, R, Galioto, A, Ballardini, G, Rendina, M, Nardelli, S, Piano, S, Elia, C, Prestianni, L, Cappa, F, Cesarini, L, Simone, L, Pasquale, C, Cavallin, M, Andrealli, A, Fidone, F, Ruggeri, M, Roncadori, A, Baldassarre, M, Tufoni, M, Zaccherini, G, Bernardi, M, Domenicali, M, Giannone, F, Merli, M, Gioia, S, Fasolato, S, Sticca, A, Campion, D, Risso, A, Saracco, G, Maiorca, D, Rizzotto, A, Lanzi, A, Neri, E, Visani, A, Mastroianni, A, Alberti, A, Mazzarelli, C, Vangeli, M, Marzioni, M, Capretti, F, Kostandini, A, Magini, G, Colpani, M, Laffi, G, Gabbani, T, Marsico, M, Zappimbulso, M, Petruzzi, J, Calvaruso, V, Parrella, G, Caporaso, N, Auriemma, F, Guarino, M, Pugliese, F, Gasbarrini, A, Leo, P, De Leonardis, F, Pecchioli, A, Rossi, P, Raimondo, G, Negri, E, Dallio, M, Loguercio, C, Conte, D, Celli, N, Bringiotti, R, Castellaneta, N, and Salerno, F

Subjects
Liver Cirrhosis, Male, Time Factors, Cirrhosis, Kaplan-Meier Estimate, law.invention, ascites, 0302 clinical medicine, Hepatorenal syndrome, Randomized controlled trial, Furosemide, law, Ascites, Clinical endpoint, Paracentesis, Diuretics, albumin, decompensated cirrhosi, Mineralocorticoid Receptor Antagonists, Settore MED/12 - Gastroenterologia, Medicine (all), Hazard ratio, General Medicine, Middle Aged, Survival Rate, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Quality-Adjusted Life Years, medicine.symptom, Hyponatremia, medicine.medical_specialty, 03 medical and health sciences, Albumins, Internal medicine, medicine, Humans, Survival rate, albumin, Aged, business.industry, cirrhosis, medicine.disease, Clinical trial, albumin, cirrhosis, ascites, liver decompensation, Quality of Life, Hyperkalemia, business, Esophagus Varices, Portal Hypertension, Varicosis
Abstract

Background Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. Methods We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794. Findings From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40–0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related adverse events. Interpretation In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Funding Italian Medicine Agency. Copyright © 2018 Elsevier Ltd. All rights reserved.

Published
2018

8. Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy

Author

Bertoli, Ada, Sorbo, Maria Chiara, Aragri, Marianna, Lenci, Ilaria, Teti, Elisabetta, Polilli, Ennio, Di Maio, Velia Chiara, Gianserra, Laura, Biliotti, Elisa, Masetti, Chiara, Magni, Carlo F., Babudieri, Sergio, Nicolini, Laura A., Milana, Martina, Cacciatore, Pierluigi, Sarmati, Loredana, Pellicelli, Adriano, Paolucci, Stefania, Craxì, Antonio, Morisco, Filomena, Palitti, Valeria Pace, Siciliano, Massimo, Coppola, Nicola, Iapadre, Nerio, Puoti, Massimo, Rizzardini, Giuliano, Taliani, Gloria, Pasquazzi, Caterina, Andreoni, Massimo, Parruti, Giustino, Angelico, Mario, Perno, Carlo Federico, Cento, Valeria, Ceccherini-Silberstein, Francesca, Andreone, Pietro, Baldanti, Fausto, Barbarini, Giorgio, Boccaccio, Vincenzo, Boglione, Lucio, Bolis, Matteo, Bonora, Stefano, Borghi, Vanni, Brancaccio, Giuseppina, Bruno, Savino, Bruzzone, Bianca, Calvaruso, Vincenza, Caporaso, Nicola, Ciaccio, Antonio, Ciancio, Alessia, Colombatto, Piero, Cozzolongo, Raffaele, D'Ambrosio, Cecilia, D'Ettorre, Gabriella, De Leonardis, Francesco, De Luca, Andrea, Di Biagio, Antonio, Di Perri, Giovanni, Francioso, Simona, Gaeta, Giovanni Battista, Gasbarrini, Antonio, Ghisetti, Valeria, Giorgini, Alessia, Grieco, Antonio, Gubertini, Guido, Gulminetti, Roberto, Lambiase, Lara, Landonio, Simona, Lichtner, Miriam, Maida, Ivana, Marenco, Simona, Marinaro, Letizia, Maserati, Renato, Melis, Michela, Menzaghi, Barbara, Meregalli, Elisa, Micheli, Valeria, Niero, Fosca, Paoloni, Maurizio, Pieri, Alessandro, Rendina, Maria, Romagnoli, Dante, Rossetti, Barbara, Ruggiero, Tina, Sangiovanni, Vincenzo, Starace, Mario, Sticchi, Laura, Tarquini, Pierluigi, Toniutto, Pierluigi, Vullo, Vincenzo, Zazzi, Maurizio, HCV Virology Italian Resistance Network, Bertoli A1, Sorbo MC1, Aragri M1, Lenci I2, Teti E3, Polilli E4, Di Maio VC1, Gianserra L5, Biliotti E6, Masetti C2, Magni CF7, Babudieri S8, Nicolini LA9, Milana M2, Cacciatore P4, Sarmati L3, Pellicelli A10, Paolucci S11, Craxì A, Morisco F13, Palitti VP14, Siciliano M15, Coppola N16, Iapadre N17, Puoti M18, Rizzardini G7, Taliani G6, Pasquazzi C5, Andreoni M3, Parruti G4, Angelico M2, Perno CF19, Cento V20, Ceccherini-Silberstein F1, HCV Virology Italian Resistance Network (VIRONET-C)., Bertoli, Ada, Sorbo, Maria Chiara, Aragri, Marianna, Lenci, Ilaria, Teti, Elisabetta, Polilli, Ennio, Di Maio, Velia Chiara, Gianserra, Laura, Biliotti, Elisa, Masetti, Chiara, Magni, Carlo F., Babudieri, Sergio, Nicolini, Laura A., Milana, Martina, Cacciatore, Pierluigi, Sarmati, Loredana, Pellicelli, Adriano, Paolucci, Stefania, Craxì, Antonio, Morisco, Filomena, Palitti, Valeria Pace, Siciliano, Massimo, Coppola, Nicola, Iapadre, Nerio, Puoti, Massimo, Rizzardini, Giuliano, Taliani, Gloria, Pasquazzi, Caterina, Andreoni, Massimo, Parruti, Giustino, Angelico, Mario, Perno, Carlo Federico, Cento, Valeria, Ceccherini-Silberstein, Francesca, Andreone, Pietro, Baldanti, Fausto, Barbarini, Giorgio, Boccaccio, Vincenzo, Boglione, Lucio, Bolis, Matteo, Bonora, Stefano, Borghi, Vanni, Brancaccio, Giuseppina, Bruno, Savino, Bruzzone, Bianca, Calvaruso, Vincenza, Caporaso, Nicola, Ciaccio, Antonio, Ciancio, Alessia, Colombatto, Piero, Cozzolongo, Raffaele, D'Ambrosio, Cecilia, D'Ettorre, Gabriella, De Leonardis, Francesco, De Luca, Andrea, Di Biagio, Antonio, Di Perri, Giovanni, Francioso, Simona, Gaeta, Giovanni Battista, Gasbarrini, Antonio, Ghisetti, Valeria, Giorgini, Alessia, Grieco, Antonio, Gubertini, Guido, Gulminetti, Roberto, Lambiase, Lara, Landonio, Simona, Lichtner, Miriam, Maida, Ivana, Marenco, Simona, Marinaro, Letizia, Maserati, Renato, Melis, Michela, Menzaghi, Barbara, Meregalli, Elisa, Micheli, Valeria, Niero, Fosca, Paoloni, Maurizio, Pieri, Alessandro, Rendina, Maria, Romagnoli, Dante, Rossetti, Barbara, Ruggiero, Tina, Sangiovanni, Vincenzo, Starace, Mario, Sticchi, Laura, Tarquini, Pierluigi, Toniutto, Pierluigi, Vullo, Vincenzo, Zazzi, Maurizio, Bertoli, A, Sorbo, M, Aragri, M, Lenci, I, Teti, E, Polilli, E, Di Maio, V, Gianserra, L, Biliotti, E, Masetti, C, Magni, C, Babudieri, S, Nicolini, L, Milana, M, Cacciatore, P, Sarmati, L, Pellicelli, A, Paolucci, S, Craxi, A, Morisco, F, Palitti, V, Siciliano, M, Coppola, N, Iapadre, N, Puoti, M, Rizzardini, G, Taliani, G, Pasquazzi, C, Andreoni, M, Parruti, G, Angelico, M, Perno, C, Cento, V, Ceccherini-Silberstein, F, Andreone, P, Baldanti, F, Barbarini, G, Boccaccio, V, Boglione, L, Bolis, M, Bonora, S, Borghi, V, Brancaccio, G, Bruno, S, Bruzzone, B, Calvaruso, V, Caporaso, N, Ciaccio, A, Ciancio, A, Colombatto, P, Cozzolongo, R, D'Ambrosio, C, D'Ettorre, G, De Leonardis, F, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, G, Gasbarrini, A, Ghisetti, V, Giorgini, A, Grieco, A, Gubertini, G, Gulminetti, R, Lambiase, L, Landonio, S, Lichtner, M, Maida, I, Marenco, S, Marinaro, L, Maserati, R, Melis, M, Menzaghi, B, Meregalli, E, Micheli, V, Niero, F, Paoloni, M, Pieri, A, Rendina, M, Romagnoli, D, Rossetti, B, Ruggiero, T, Sangiovanni, V, Starace, M, Sticchi, L, Tarquini, P, Toniutto, P, Vullo, V, Zazzi, M, Sorbo, Mc, Di Maio, Vc, Magni, Cf, Nicolini, La, Craxì, A, Palitti, Vp, Perno, Cf, Gaeta, Gb, and Zazzi, M.

Subjects
Male, 0301 basic medicine, Sofosbuvir, Hepacivirus, Drug Resistance, lcsh:Medicine, Viral Nonstructural Proteins, medicine.disease_cause, Gastroenterology, Hepatitis C Virus, HCV resistance-test, chemistry.chemical_compound, 0302 clinical medicine, Genotype, Prevalence, Viral, lcsh:Science, Multidisciplinary, biology, Hepatitis C, Middle Aged, Settore MED/07 - Microbiologia e Microbiologia Clinica, Italy, Cohort, HCV, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, medicine.medical_specialty, HCV RAS, Hepatitis C virus, 03 medical and health sciences, Internal medicine, Drug Resistance, Viral, medicine, Humans, Aged, NS5A, NS5B, business.industry, lcsh:R, Hepatitis C Virus, HCV resistance-test, biology.organism_classification, medicine.disease, 030104 developmental biology, chemistry, lcsh:Q, business
Abstract

Natural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2–45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4–19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1–4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.

Published
2018

9. Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows

Author

Guarino, Maria, Sessa, Anna, Cossiga, Valentina, Morando, Federica, Caporaso, Nicola, Morisco, Filomena, Luca, Viganó, Romana, Ponziani Francesca, Maurizio, Pompili, Cillo, Umberto, Burra, Patrizia, Mescoli, Claudia, Gambato, Martina, Russo, FRANCESCO PAOLO, Vitale, Alessandro, Giuseppe, Cabibbo, Mauro, Vigano', Giovanni, Galati, Erica, Villa, Lupo, Luigi G., Maria, Rendina, Losito, Francesco, Fucilli, Fabio, Persico, Marcello, D'Ambrosio, Roberta, Sangiovanni, Angelo, Massimo, Iavarone, Brancaccio, Giuseppina, Cucchetti, Alessandro, Renzulli, Matteo, Franco, Trevisani, Miele, Luca, Grieco, Antonio, Rapaccini, Gianlodovico, Gasbarrini, Antonio, Sandri, Giovanni Battisa Levi, Melandro, Fabio, Rossi, Massimo, Quirino, Lai, Lenci, Ilaria, Manzia, Tommaso Maria, Tortora, Raffaella, Di Costanzo, Giovan Giuseppe, Ghinolfi, Davide, Rreka, Erion, Carrai, Paola, Simonetti, Natalia, Rodolfo, Sacco, Sposito, Carlo, Bhoori, Sherrie, Di Sandro, Stefano, Foschi, Francesco Giuseppe, Gardini, Andrea Casadei, Nicolini, Daniele, Mazzocato, Susanna, Alba, Kostandini, Violi, Paola, Baccarani, Umberto, Pravisani, Riccardo, Vincenzi, Valter, Maria, Guarino, Anna, Sessa, Valentina, Cossiga, Federica, Morando, Nicola, Caporaso, Filomena, Morisco, Viganó, Luca, Ponziani Francesca, Romana, Pompili, Maurizio, Umberto, Cillo, Patrizia, Burra, Claudia, Mescoli, Martina, Gambato, Russo Francesco, Paolo, Vitale, Alessandro, Cabibbo, Giuseppe, Vigano', Mauro, Galati, Giovanni, Villa, Erica, Luigi G., Lupo, Rendina, Maria, Francesco, Losito, Fabio, Fucilli, Marcello, Persico, Roberta, D'Ambrosio, Angelo, Sangiovanni, Iavarone, Massimo, Brancaccio, Giuseppina, Alessandro, Cucchetti, Matteo, Renzulli, Trevisani, Franco, Luca, Miele, Antonio, Grieco, Gianlodovico, Rapaccini, Antonio, Gasbarrini, Giovanni Battisa Levi, Sandri, Fabio, Melandro, Massimo, Rossi, Lai, Quirino, Ilaria, Lenci, Tommaso Maria, Manzia, Raffaella, Tortora, Giovan Giuseppe, Di Costanzo, Davide, Ghinolfi, Erion, Rreka, Paola, Carrai, Natalia, Simonetti, Sacco, Rodolfo, Carlo, Sposito, Sherrie, Bhoori, Stefano, Di Sandro, Francesco Giuseppe, Foschi, Andrea Casadei, Gardini, Daniele, Nicolini, Susanna, Mazzocato, Kostandini, Alba, Paola, Violi, Umberto, Baccarani, Riccardo, Pravisani, Valter, Vincenzi, Guarino, Maria, Sessa, Anna, Cossiga, Valentina, Morando, Federica, Caporaso, Nicola, Morisco, Filomena, Luca, Viganó, Romana, Ponziani Francesca, Maurizio, Pompili, Cillo, Umberto, Burra, Patrizia, Mescoli, Claudia, Gambato, Martina, Paolo, Russo Francesco, Alessandro, Vitale, Giuseppe, Cabibbo, Mauro, Vigano', Giovanni, Galati, Erica, Villa, Lupo, Luigi G., Maria, Rendina, Losito, Francesco, Fucilli, Fabio, Persico, Marcello, D'Ambrosio, Roberta, Sangiovanni, Angelo, Massimo, Iavarone, Giuseppina, Brancaccio, Cucchetti, Alessandro, Renzulli, Matteo, Franco, Trevisani, Miele, Luca, Grieco, Antonio, Rapaccini, Gianlodovico, Gasbarrini, Antonio, Sandri, Giovanni Battisa Levi, Melandro, Fabio, Rossi, Massimo, Quirino, Lai, Lenci, Ilaria, Manzia, Tommaso Maria, Tortora, Raffaella, Di Costanzo, Giovan Giuseppe, Ghinolfi, Davide, Rreka, Erion, Carrai, Paola, Simonetti, Natalia, Rodolfo, Sacco, Sposito, Carlo, Bhoori, Sherrie, Di Sandro, Stefano, Foschi, Francesco Giuseppe, Gardini, Andrea Casadei, Nicolini, Daniele, Mazzocato, Susanna, Alba, Kostandini, Violi, Paola, Baccarani, Umberto, Pravisani, Riccardo, and Vincenzi, Valter

Subjects
Oncology, Cirrhosis, Direct-acting antiviral agent, Sustained Virologic Response, Direct-acting antiviral agents, Hepatitis C virus, Hepatocellular carcinoma, Occurrence, Recurrence, Antiviral Agents, Carcinoma, Hepatocellular, Disease Progression, Hepacivirus, Hepatitis C, Chronic, Humans, Incidence, Liver, Liver Neoplasms, Neoplasm Recurrence, Local, Risk Factors, Treatment Outcome, Gastroenterology, medicine.disease_cause, DIRECT ACTING ANTIVIRALS, 0302 clinical medicine, Chronic, biology, Incidence (epidemiology), Minireviews, General Medicine, Hepatitis C, Local, Liver Neoplasm, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Human, medicine.medical_specialty, Interferon therapy, 03 medical and health sciences, Chronic hepatitis, Internal medicine, medicine, Antiviral Agent, Hepaciviru, business.industry, Risk Factor, Carcinoma, Hepatocellular, medicine.disease, biology.organism_classification, digestive system diseases, Settore MED/18 - Chirurgia Generale, Neoplasm Recurrence, business, Hepatitis C viru
Abstract

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. © 2018 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved.

Published
2018

10. Gender differences in chronic liver diseases in two cohorts of 2001 and 2014 in Italy

Author

Sagnelli, Evangelista, Stroffolini, Tommaso, Sagnelli, Caterina, Pirisi, Mario, Babudieri, Sergio, Colloredo, Guido, Russello, Maurizio, Coppola, Nicola, Gaeta, Giovanni Battista, Cacopardo, Bruno, De Luca, Massimo, Almasio, Piero Luigi, Andriulli, Angelo, Brancaccio, Giuseppina, Furlan, Caterina, Licata, Anna, Morisco, Filomena, Pisaturo, Mariantonietta, Rosina, Floriano, Rusello, Maurizio, Santantonio, Teresa, Smedile, Antonina, Sagnelli, Evangelista, Stroffolini, Tommaso, Sagnelli, Caterina, Pirisi, Mario, Babudieri, Sergio, Colloredo, Guido, Russello, Maurizio, Coppola, Nicola, Gaeta, Giovanni Battista, Cacopardo, Bruno, De Luca, Massimo, Almasio, Piero Luigi, Andriulli, Angelo, Brancaccio, Giuseppina, Furlan, Caterina, Licata, Anna, Morisco, Filomena, Pisaturo, Mariantonietta, Rosina, Floriano, Rusello, Maurizio, Santantonio, Teresa, and Smedile, Antonina

Subjects
Alcoholic liver disease, Pathology, Cirrhosis, liver diseases, Hepatocellular carcinoma, Prevalence, Chronic liver disease, Gastroenterology, 0302 clinical medicine, cohort studies, Epidemiology, middle aged, 030212 general & internal medicine, humans, Chronic liver diseases, HBV infection, Chronic hepatitis, adult, General Medicine, Hepatitis C, Hepatitis B, HCV infection, aged, Infectious Diseases, Italy, young adult, 030211 gastroenterology & hepatology, Cohort study, Microbiology (medical), medicine.medical_specialty, prevalence, 03 medical and health sciences, Internal medicine, medicine, Liver Diseases, Alcoholic, Alcoholic liver diseases, business.industry, medicine.disease, prospective studies, sex factors, Chronic hepatiti, hepatitis B, hepatitis C, business, chronic disease, alcoholic liver diseases, chronic hepatitis, chronic liver diseases, hepatocellular carcinoma, liver diseases, alcoholic, alcoholic
Abstract

Background: Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014). Methods: The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods. Results: The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely to show HCV infection alone (48.0% vs. 67.9%). A male preponderance was observed in HBV-related cases (1.99) and in alcoholic-related cases (2.3), a preponderance observed both in the 2001 and in 2014 cases. In HCV-related cases, however, females predominated in 2001 (M/F 0.9) and males in 2014 (M/F 1.5).The rate of cirrhosis in alcohol-related etiology was close to 36% in both genders, a finding much higher than that observed for both sexes in HBV and HCV etiologies.Both males and females enrolled in 2014 were older (pÂ

Published
2017

11. The evolutionary scenario of hepatocellular carcinoma in Italy: an update

Author

Bucci, Laura, Garuti, Francesca, Lenzi, Barbara, Pecorelli, Anna, Farinati, Fabio, Giannini, Edoardo G., Granito, Alessandro, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cammà, Calogero, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Bernardi, Mauro, Trevisani, Franco, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Napoli, Lucia, Negrini, Giulia, Piscaglia, Fabio, Serra, Carla, Tovoli, Francesco, Marafatto, Filippo, Murer, Francesca, Peserico, Giulia, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Poggio, Paolo Del, Olmi, Stefano, De Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Barcellona, Maria Rosa, Cabibbo, Giuseppe, Costantino, Andrea, Maida, Marcello, Affronti, Andrea, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, Dall’Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Porro, Emanuela, Guarino, Maria, Gemini, Stefano, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Aburas, Sami, Inghilesi, Andrea Lorenzo, Bucci, Laura, Garuti, Francesca, Lenzi, Barbara, Pecorelli, Anna, Farinati, Fabio, Giannini, Edoardo G, Granito, Alessandro, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cammà, Calogero, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, GERARDO ANTONIO PIO, Colecchia, Antonio, Bernardi, Mauro, Trevisani, Franco, Bucci, L, Garuti, F, Lenzi, B, Granito, A, Zoli, M, Colecchia, A, Bernardi, M, Trevisani, F, Biselli, M, Caraceni, P, Cucchetti, A, Gramenzi, A, Piscaglia, F., Bucci, L., Garuti, F., Lenzi, B., Pecorelli, A., Farinati, F., Giannini, E., Granito, A., Ciccarese, F., Rapaccini, G., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cammà, C., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnù, L., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F., Missale, G., Masotto, A., Nardone, G., Colecchia, A., Bernardi, M., and Trevisani, F.

Subjects
Oncology, Male, Etiology, Databases, Factual, Radiofrequency ablation, medicine.medical_treatment, law.invention, 0302 clinical medicine, law, Epidemiology, epidemiology, hepatocellular carcinoma, survival, treatment, Hepatology, Aged, 80 and over, Surveillance, Liver Neoplasms, Middle Aged, Prognosis, Italy, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Catheter Ablation, 030211 gastroenterology & hepatology, Female, alpha-Fetoproteins, Liver cancer, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, 03 medical and health sciences, Young Adult, Age Distribution, Internal medicine, medicine, Humans, Sex Distribution, Aged, Neoplasm Staging, Retrospective Studies, Cirrhosi, business.industry, Cancer stage, Settore MED/09 - MEDICINA INTERNA, Cancer, medicine.disease, Surgery, Percutaneous ethanol injection, business
Abstract

Background and aims Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of etiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years. Methods Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centers from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000-2004, 2005-2009 and 2010-2014). Results The main results were: 1) progressive patient aging; 2) progressive expansion of non-viral cases and, namely, of “metabolic” hepatocellular carcinomas; 3) increasing proportion of hepatocellular carcinoma diagnosed during a correct (semiannual) surveillance program; 4) favourable cancer stage migration; 4) increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; 5) improved outcomes of ablative and transarterial treatments; 6) improved overall survival (adjusted for the lead time in surveyed patients), particularly after 2009, of both viral and non-viral patients presenting with an early or intermediate stage hepatocellular carcinoma. Conclusions During the last 15 years several etiological and clinical features of hepatocellular carcinoma patients have changed, as their management. The observed improvement of overall survival was due both to the wider use of semiannual surveillance, expanding the proportion of tumors that qualified for curative treatments, and to the improved outcome of locoregional treatments. This article is protected by copyright. All rights reserved.

Published
2017

12. Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma

Author

Cabibbo, Giuseppe, Petta, Salvatore, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G., Negrini, Giulia, Ciccarese, Francesca, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Benvegnã¹, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Persico, Marcello, Craxã¬, Antonio, Trevisani, Franco, Cammã&nbsp, Calogero, Cabibbo, G., Petta, S., Barbara, M., Attardo, S., Bucci, L., Farinati, F., Giannini, E., Negrini, G., Ciccarese, F., Rapaccini, G., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Mega, A., Morisco, F., Benvegnã¹, L., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F., Olivani, A., Masotto, A., Nardone, G., Colecchia, A., Persico, M., Craxi, A., Trevisani, F., Camma', C., G. Cabibbo, S. Petta, M. Barbara, S. Attardo, L. Bucci, F. Farinati, E. G. Giannini, G. Negrini, F. Ciccarese, G. L. Rapaccini, M. Di Marco, E. Caturelli, M. Zoli, F. Borzio, R. Sacco, R. Virdone, F. Marra, A. Mega, F. Morisco, L. Benvegnù, A. Gasbarrini, G. Svegliati-Baroni, F. G. Foschi, A. Olivani, A. Masotto, G. Nardone, A. Colecchia, M. Persico, A. Craxì, F. Trevisani, C. Cammà, Cabibbo, Giuseppe, Petta, Salvatore, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G, Negrini, Giulia, Ciccarese, Francesca, Lodovico Rapaccini, Gian, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra Mega, Fabio Andrea, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Giuseppe Foschi, Francesco, Olivani, Andrea, Masotto, Alberto, Nardone, GERARDO ANTONIO PIO, Colecchia, Antonio, Persico, Marcello, Craxì, Antonio, Trevisani, Franco, and Cammà, Calogero

Subjects
Liver Cirrhosis, Male, Hepatocellular Carcinoma, Liver Cirrhosis, hepatitis C virus, Survival, direct-acting antiviral agents, Survival rate, Cirrhosis, Antiviral agent, Gastroenterology, Liver cirrhosi, 0302 clinical medicine, Recurrence, Hepatic decompensation, Hepatitis C Virus (HCV), Hepatocellular carcinoma (HCC), Prognosis, Recurrences, Sustained virological response (SVR), overall survival (OS), Overall survival, Liver Neoplasms, Hepatitis C, Middle Aged, Sustained virological response, Local, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, Antiviral agents, Carcinoma, hepatocellular, Liver cirrhosis, Aged, Carcinoma, Hepatocellular, Humans, Neoplasm Recurrence, Local, Proportional Hazards Models, Liver cancer, medicine.medical_specialty, Prognosi, Settore MED/12 - GASTROENTEROLOGIA, 03 medical and health sciences, hepatocellular, Internal medicine, medicine, Early Hepatocellular Carcinoma, Hepatology, business.industry, Carcinoma, Hepatocellular, medicine.disease, digestive system diseases, Neoplasm Recurrence, Liver function, business
Abstract

Background & Aims Assessment of long-term outcome is required in hepatitis C virus (HCV)-infected patients with cirrhosis, who have been successfully treated for Barcelona Clinic Liver Cancer (BCLC) stage A hepatocellular carcinoma (HCC). However, problems arise due to the lack of models accounting for early changes during follow-up. The aim of this study was to estimate the impact of early events (HCC recurrence or hepatic decompensation within 12Âmonths of complete radiological response) on 5-year overall survival (OS) in a large cohort of patients with HCV and cirrhosis, successfully treated HCC. Methods A total of 328 consecutive Caucasian patients with HCV-related cirrhosis and BCLC stage 0/A HCC who had complete radiological response after curative resection or thermal ablation were prospectively recruited to this study. Primary endpoint of the study was 5-year OS. Independent baseline and time-dependent predictors of 5-year OS were identified by Cox model. Results The observed 5-year survival rate was 44%. The observed HCC early recurrence and early hepatic decompensation rate were 21% and 10%, respectively. Early hepatic decompensation (Hazard Ratio [HR] 7.52; 95% confidence intervals (CI): 1.23–13.48) and HCC early recurrence as time-dependent covariates (HR 2.50; 95%CI: 1.23–5.05), presence of esophageal varices at baseline (HR 1.66; 95% CI: 1.02–2.70) and age (HR 1.04; 95% CI: 1.02–1.07) were significantly associated with the 5-year OS. Conclusion Survival in HCV-infected patients with cirrhosis and successfully treated HCC is influenced by early hepatic decompensation. Our study indirectly suggests that direct-acting antiviral agents could improve OS of HCC patients through long-term preservation of liver function, resulting in a lower cirrhosis-related mortality and a greater change of receiving curative treatments. Lay summary Survival in hepatitis C virus (HCV) infected patients with cirrhosis and successfully treated hepatocellular carcinoma (HCC), is mainly influenced by early hepatic decompensation. HCV eradication after treatment with new direct-acting antiviral agents could improve overall survival of HCC patients through long-term preservation of liver function.

Published
2017

13. Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study

Author

Petta, Salvatore, Marzioni, Marco, Russo, Pierluigi, Aghemo, Alessio, Alberti, Alfredo, ASCIONE, ANTONIO, Antinori, Andrea, Bruno, Raffaele, Bruno, Savino, Chirianni, Antonio, Gaeta, Giovanni Battista, Giannini, Edoardo G, Merli, Manuela, Messina, Vincenzo, Montilla, Simona, Perno, Carlo Federico, Puoti, Massimo, Raimondo, Giovanni, Rendina, Maria, Silberstein, Francesca Ceccherini, Villa, Erica, Zignego, Anna Linda, Pani, Luca, Craxì, Antonio, Tabone, Marco, Andreoni, Massimo, Teti, Elisabetta, Angelico, Mario, Persico, Marcello, Masarone, Mario, Chiodera, Aledssandro, Solinas, Attilio, delle Monache, Marco, Cecere, Roberto, Maria Schimizzi, Anna, Piovesan, Sara, Campagnolo, Davide, Chiara Piras, Maria, Zolfino, Teresa, Paolo Russo, Francesca, Morelli, Olivia, Sangiovanni, Vincenzo, Onofrio, Mirella, Iodice, Valentina, Izzi, Antonio, Pirisi, Massimo, Danieli, Elena, Vinci, Maria, Rizzardini, Giuliano, Fagiuoli, Stefano, Pasulo, Luisa, D'Arminio Monforte, Antonella, Zuin, Massimo, Giorgini, Alessia, Simeone, Filomena, Piali, Guido, Lo Guercio, Carmela, Federico, Alessandro, Brancaccio, Giuseppina, Marrone, Aldo, Abbati, Giuseppe, Boarini, Chiara, Borghi, Vanni, Bernabucci, Veronica, Corti, Giampaolo, Monti, Monica, Rizzetto, Mario, Martini, Silvia, Andreone, Pietro, Gianstefani, Alice, Lenzi, Marco, Verucchi, Gabriella, Toniutto, Pierluigi, Borgia, Guglielmo, Caporaso, Nicola, Morisco, Filomena, Nardone, Gaetano, Angrisani, Debora, Giacometti, Andrea, Benedetti, Antonio, Tarantino, Giuseppe, Marsetti, Fabio, Tavio, Marcello, Novara, Sergio, Antonia Santantonio, Teresa, Serviddio, Gaetano, Brunetto, Maurizia, Coco, Barbara, Angarano, Gioacchino, Milella, Michele, BARONE, MICHELE, Di Leo, Alfredo, Ettore Sansonno, Domenico, Cacciola, Irene, Boffa, Nicola, Saracco, Giorgio, Di Biagio, Antonio, Picciotto, Antonino, de Luca, Andrea, Calvaruso, Vincenza, Corradori, Silvia, Ferrari, Carlo, Orlandini, Alessandra, Maida, Ivana, Torti, Carlo, Chessa, Luchino, Felder, Martina, Vespasiani Gentilucci, Umberto, Angeli, Paolo, Romano, Antonietta, Ludovico Rapaccini, Gian, Miele, Luca, Cima, Serena, Luisa Russo, Maria, Cozzolongo, Raffaele, Onnelli, Giovanna, D'Offizi, Giampiero, Lionetti, Raffaella, Montalbano, Marzia, Guerra, Michele, Di Perri, Giovanni, Boglione, Lucio, Capra, Franco, Carolo, Giada, Ieluzzi, Donatella, Antonini, Cinzia, Termite, Antonio, Madonia, Salvatore, Tarquini, Pierluigi, Parruti, Giustino, Vecchiet, Giacomo, Falasca, Katia, Menzaghi, Barbara, Quirino, Tiziana, Dentone, Chiara, Maria Piscaglia, Anna, Rossi, Cristina, Giordani, Maria, Fontanella, Luca, Cassola, Giovanni, Russello, Maurizio, Cristaudo, Antonio, Giacomet, Vania, Colombo, Massimo, Donato, Francesca, Durante, Emanuele, Cosco, Lucio, Marignani, Massimo, Quartini, Mariano, Memoli, Massimo, Ganga, Roberto, Ponti, Laura, Soria, Alessandro, Grazia Rumi, Maria, Gulminetti, Roberto, Maserati, Renato, Mondelli, Mario, Lazzarin, Adriano, Rita Parisi, Maria, Canovari, Benedetta, Avancini, Ivo, Pravadelli, Cecilia, Blanc, Pier, Pasquazzi, Caterina, Maria Mastroianni, Claudio, Lichtner, Myriam, Distefano, Marco, Magnani, Silvia, Paganin, Simona, Erne, Elke, Gatti, Pietro, Tundi, Paolo, Calabrese, Paolo, Gasbarrini, Antonio, Grieco, Antonio, Coppola, Nicola, Del Poggio, Paolo, Levrero, Massimo, Talliani, Gloria, Vullo, Vincenzo, Cauda, Roberto, La Monica, Silvia, Potenza, Domenico, Rizzo, Salvatore, Castelli, Francesco, Marie Pigozzi, Grazielle, Ciancio, Alessia, Romagnoli, Dante, Barchetti, Federica, Ivanovic, Jelena, Longo, Olimpia, Petraglia, Sandra, Paola Trotta, Maria, NARDONE, GERARDO ANTONIO PIO, Petta, Salvatore, Marzioni, Marco, Russo, Pierluigi, Aghemo, Alessio, Alberti, Alfredo, Ascione, Antonio, Antinori, Andrea, Bruno, Raffaele, Bruno, Savino, Chirianni, Antonio, Gaeta, Giovanni Battista, Giannini, Edoardo G, Merli, Manuela, Messina, Vincenzo, Montilla, Simona, Perno, Carlo Federico, Puoti, Massimo, Raimondo, Giovanni, Rendina, Maria, Silberstein, Francesca Ceccherini, Villa, Erica, Zignego, Anna Linda, Pani, Luca, Craxì, Antonio, Tabone, Marco, Andreoni, Massimo, Teti, Elisabetta, Angelico, Mario, Persico, Marcello, Masarone, Mario, Chiodera, Aledssandro, Solinas, Attilio, delle Monache, Marco, Cecere, Roberto, Maria Schimizzi, Anna, Piovesan, Sara, Campagnolo, Davide, Chiara Piras, Maria, Zolfino, Teresa, Paolo Russo, Francesca, Morelli, Olivia, Sangiovanni, Vincenzo, Onofrio, Mirella, Iodice, Valentina, Izzi, Antonio, Pirisi, Massimo, Danieli, Elena, Vinci, Maria, Rizzardini, Giuliano, Fagiuoli, Stefano, Pasulo, Luisa, D'Arminio Monforte, Antonella, Zuin, Massimo, Giorgini, Alessia, Simeone, Filomena, Piali, Guido, Lo Guercio, Carmela, Federico, Alessandro, Brancaccio, Giuseppina, Marrone, Aldo, Abbati, Giuseppe, Boarini, Chiara, Borghi, Vanni, Bernabucci, Veronica, Corti, Giampaolo, Monti, Monica, Rizzetto, Mario, Martini, Silvia, Andreone, Pietro, Gianstefani, Alice, Lenzi, Marco, Verucchi, Gabriella, Toniutto, Pierluigi, Borgia, Guglielmo, Caporaso, Nicola, Morisco, Filomena, Nardone, Gaetano, Angrisani, Debora, Giacometti, Andrea, Benedetti, Antonio, Tarantino, Giuseppe, Marsetti, Fabio, Tavio, Marcello, Novara, Sergio, Antonia Santantonio, Teresa, Serviddio, Gaetano, Brunetto, Maurizia, Coco, Barbara, Angarano, Gioacchino, Milella, Michele, Barone, Michele, Di Leo, Alfredo, Ettore Sansonno, Domenico, Cacciola, Irene, Boffa, Nicola, Saracco, Giorgio, Di Biagio, Antonio, Picciotto, Antonino, de Luca, Andrea, Calvaruso, Vincenza, Corradori, Silvia, Ferrari, Carlo, Orlandini, Alessandra, Maida, Ivana, Torti, Carlo, Chessa, Luchino, Felder, Martina, Vespasiani Gentilucci, Umberto, Angeli, Paolo, Romano, Antonietta, Ludovico Rapaccini, Gian, Miele, Luca, Cima, Serena, Luisa Russo, Maria, Cozzolongo, Raffaele, Onnelli, Giovanna, D'Offizi, Giampiero, Lionetti, Raffaella, Montalbano, Marzia, Guerra, Michele, Di Perri, Giovanni, Boglione, Lucio, Capra, Franco, Carolo, Giada, Ieluzzi, Donatella, Antonini, Cinzia, Termite, Antonio, Madonia, Salvatore, Tarquini, Pierluigi, Parruti, Giustino, Vecchiet, Giacomo, Falasca, Katia, Menzaghi, Barbara, Quirino, Tiziana, Dentone, Chiara, Maria Piscaglia, Anna, Rossi, Cristina, Giordani, Maria, Fontanella, Luca, Cassola, Giovanni, Russello, Maurizio, Cristaudo, Antonio, Giacomet, Vania, Colombo, Massimo, Donato, Francesca, Durante, Emanuele, Cosco, Lucio, Marignani, Massimo, Quartini, Mariano, Memoli, Massimo, Ganga, Roberto, Ponti, Laura, Soria, Alessandro, Grazia Rumi, Maria, Gulminetti, Roberto, Maserati, Renato, Mondelli, Mario, Lazzarin, Adriano, Rita Parisi, Maria, Canovari, Benedetta, Avancini, Ivo, Pravadelli, Cecilia, Blanc, Pier, Pasquazzi, Caterina, Maria Mastroianni, Claudio, Lichtner, Myriam, Distefano, Marco, Magnani, Silvia, Paganin, Simona, Erne, Elke, Gatti, Pietro, Tundi, Paolo, Calabrese, Paolo, Gasbarrini, Antonio, Grieco, Antonio, Coppola, Nicola, Del Poggio, Paolo, Levrero, Massimo, Talliani, Gloria, Vullo, Vincenzo, Cauda, Roberto, La Monica, Silvia, Potenza, Domenico, Rizzo, Salvatore, Castelli, Francesco, Marie Pigozzi, Grazielle, Ciancio, Alessia, Romagnoli, Dante, Barchetti, Federica, Ivanovic, Jelena, Longo, Olimpia, Petraglia, Sandra, Paola Trotta, Maria, Petta, S., Marzioni, M., Russo, P., Aghemo, A., Alberti, A., Ascione, A., Antinori, A., Bruno, R., Bruno, S., Chirianni, A., Gaeta, G., Giannini, E., Merli, M., Messina, V., Montilla, S., Perno, C., Puoti, M., Raimondo, G., Rendina, M., Silberstein, F., Villa, E., Zignego, A., Pani, L., Craxi, A., Tabone, M., Andreoni, M., Teti, E., Angelico, M., Persico, M., Masarone, M., Chiodera, A., Solinas, A., delle Monache, M., Cecere, R., Maria Schimizzi, A., Piovesan, S., Campagnolo, D., Chiara Piras, M., Zolfino, T., Paolo Russo, F., Morelli, O., Sangiovanni, V., Onofrio, M., Iodice, V., Izzi, A., Pirisi, M., Danieli, E., Vinci, M., Rizzardini, G., Fagiuoli, S., Pasulo, L., D'Arminio Monforte, A., Zuin, M., Giorgini, A., Simeone, F., Piali, G., Lo Guercio, C., Federico, A., Brancaccio, G., Marrone, A., Abbati, G., Boarini, C., Borghi, V., Bernabucci, V., Corti, G., Monti, M., Rizzetto, M., Martini, S., Andreone, P., Gianstefani, A., Lenzi, M., Verucchi, G., Toniutto, P., Borgia, G., Caporaso, N., Morisco, F., Nardone, G., Angrisani, D., Giacometti, A., Benedetti, A., Tarantino, G., Marsetti, F., Tavio, M., Novara, S., Antonia Santantonio, T., Serviddio, G., Brunetto, M., Coco, B., Angarano, G., Milella, M., Barone, M., Di Leo, A., Ettore Sansonno, D., Cacciola, I., Boffa, N., Saracco, G., Di Biagio, A., Picciotto, A., de Luca, A., Calvaruso, V., Corradori, S., Ferrari, C., Orlandini, A., Maida, I., Torti, C., Chessa, L., Felder, M., Vespasiani Gentilucci, U., Angeli, P., Romano, A., Ludovico Rapaccini, G., Miele, L., Cima, S., Luisa Russo, M., Cozzolongo, R., Onnelli, G., D'Offizi, G., Lionetti, R., Montalbano, M., Guerra, M., Di Perri, G., Boglione, L., Capra, F., Carolo, G., Ieluzzi, D., Antonini, C., Termite, A., Madonia, S., Tarquini, P., Parruti, G., Vecchiet, G., Falasca, K., Menzaghi, B., Quirino, T., Dentone, C., Maria Piscaglia, A., Rossi, C., Giordani, M., Fontanella, L., Cassola, G., Russello, M., Cristaudo, A., Giacomet, V., Colombo, M., Donato, F., Durante, E., Cosco, L., Marignani, M., Quartini, M., Memoli, M., Ganga, R., Ponti, L., Soria, A., Grazia Rumi, M., Gulminetti, R., Maserati, R., Mondelli, M., Lazzarin, A., Rita Parisi, M., Canovari, B., Avancini, I., Pravadelli, C., Blanc, P., Pasquazzi, C., Maria Mastroianni, C., Lichtner, M., Distefano, M., Magnani, S., Paganin, S., Erne, E., Gatti, P., Tundi, P., Calabrese, P., Gasbarrini, A., Grieco, A., Coppola, N., Del Poggio, P., Levrero, M., Talliani, G., Vullo, V., Cauda, R., La Monica, S., Potenza, D., Rizzo, S., Castelli, F., Marie Pigozzi, G., Ciancio, A., Romagnoli, D., Barchetti, F., Ivanovic, J., Longo, O., Petraglia, S., Paola Trotta, M., Savino, Bruno, Nardone, GERARDO ANTONIO PIO, Petta, S, Marzioni, M, Russo, P, Aghemo, A, Alberti, A, Ascione, A, Antinori, A, Bruno, R, Bruno, S, Chirianni, A, Gaeta, G, Giannini, E, Merli, M, Messina, V, Montilla, S, Perno, C, Puoti, M, Raimondo, G, Rendina, M, Silberstein, F, Villa, E, Zignego, A, Pani, L, Craxì, A, and Fagiuoli, S

Subjects
Cyclopropanes, Compassionate Use Trials, Liver Cirrhosis, Male, chemistry.chemical_compound, 0302 clinical medicine, 2-Naphthylamine, HCV, direct-acting antiviral, mixed cryoglobulinemia, RBV, Anilides, 030212 general & internal medicine, Longitudinal Studies, Prospective Studies, Chronic, Adult, Aged, Antiviral Agents, Carbamates, Drug Therapy, Combination, Female, Genotype, Hepatitis C, Chronic, Humans, Macrocyclic Compounds, Middle Aged, Ribavirin, Ritonavir, Sulfonamides, Treatment Outcome, Uracil, Settore MED/12 - Gastroenterologia, Dasabuvir, HCV DAA, Gastroenterology, virus diseases, Valine, Settore MED/07 - Microbiologia e Microbiologia Clinica, Hepatitis C, Hepatology, Combination, 030211 gastroenterology & hepatology, medicine.drug, medicine.medical_specialty, Proline, Lactams, Macrocyclic, Hepatitis C virus genotype 1, Hepatitis C virus genotype 4, decompensated liver cirrhosis, antiviral therapy, dasabuvir, ombitasvir, paritaprevir, 03 medical and health sciences, Drug Therapy, Internal medicine, medicine, Decompensation, Adverse effect, business.industry, Virology, Ombitasvir, Clinical trial, chemistry, Paritaprevir, business
Abstract

Summary Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. Findings 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4·76 [95% CI 1·83–12·3]; p=0·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring in 36 (5%) patients. Interpretation Our findings suggest that the safety and effectiveness of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin in patients with HCV genotype 1 or 4 infection and cirrhosis at high risk of decompensation in a real-life setting are similar to those reported in clinical trials. The concordance with clinical trials provides reassurance that the reported efficacy of this treatment in clinical trials will translate to its use in routine clinical practice. Funding Dipartimento Biomedico di Medicina Interna e Specialistica dell'Universita di Palermo.

Published
2017

14. Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies

Author

Di Maio, Velia C., Cento, Valeria, Lenci, Ilaria, Aragri, Marianna, Rossi, Piera, Barbaliscia, Silvia, Melis, Michela, Verucchi, Gabriella, Magni, Carlo F., Teti, Elisabetta, Bertoli, Ada, Antonucci, Francescopaolo, Bellocchi, Maria C., Micheli, Valeria, Masetti, Chiara, Landonio, Simona, Francioso, Simona, Santopaolo, Francesco, Pellicelli, Adriano M., Calvaruso, Vincenza, Gianserra, Laura, Siciliano, Massimo, Romagnoli, Dante, Cozzolongo, Raffaele, Grieco, Antonio, Vecchiet, Jacopo, Morisco, Filomena, Merli, Manuela, Brancaccio, Giuseppina, Di Biagio, Antonio, Loggi, Elisabetta, Mastroianni, Claudio Maria, Pace Palitti, Valeria, Tarquini, Pierluigi, Puoti, Massimo, Taliani, Gloria, Sarmati, Loredana, Picciotto, Antonino, Vullo, Vincenzo, Caporaso, Nicola, Paoloni, Maurizio, Pasquazzi, Caterina, Rizzardini, Giuliano, Parruti, Giustino, Craxì, Antonio, Babudieri, Sergio, Andreoni, Massimo, Angelico, Mario, Perno, Carlo F., Ceccherini Silberstein, Francesca, Mariani, R., Iapadre, N., Grimaldi, A., Cozzolongo, R., Andreone, P., Verucchi, G., Menzaghi, B., Quirino, T., Pisani, V., Torti, MARIA CHIARA, Vecchiet, J., Bruzzone, B., De Maria, A., Marenco, S., Nicolini, L. A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, Miriam, Aghemo, A., Boccaccio, V., Bruno, S., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Lleo, A., Magni, C. F., Mancon, A., Monico, S., Niero, F., Russo, M. L., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Gaeta, G. B., Lembo, V., Sangiovanni, V., Di Marco, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pieri, A., Polilli, E., Sozio, F., Antenucci, F., Aragri, M., Baiocchi, L., Barbaliscia, S., Biliotti, Elisa, Biolato, M., Carioti, L., Ceccherini Silberstein, F., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Leonardis, F., De Sanctis, A., Di Maio, V. C., Di Paolo, D., Furlan, Caterina, Gallo, P., Gasbarrini, A., Giannelli, V., Grieco, S., Lambiase, L., Lattanzi, B., Lenci, I., Lula, R., Malagnino, V., Manuelli, M., Miglioresi, L., Milana, M., Moretti, A., Nosotti, L., Palazzo, Donatella, Pellicelli, A., Romano, M., Sarrecchia, C., Sforza, D., Sorbo, M. C., Spaziante, M., Svicher, V., Tisone, G., Vespasiani Gentilucci, U., D'Adamo, G., Mangia, A., Maida, I., Mura, M. S., Falconi, L., Di Giammartino, D., Di Maio, V., Cento, V., Lenci, I., Aragri, M., Rossi, P., Barbaliscia, S., Melis, M., Verucchi, G., Magni, C., Teti, E., Bertoli, A., Antonucci, F., Bellocchi, M., Micheli, V., Masetti, C., Landonio, S., Francioso, S., Santopaolo, F., Pellicelli, A., Calvaruso, V., Gianserra, L., Siciliano, M., Romagnoli, D., Cozzolongo, R., Grieco, A., Vecchiet, J., Morisco, F., Merli, M., Brancaccio, G., Di Biagio, A., Loggi, E., Mastroianni, C., Pace Palitti, V., Tarquini, P., Puoti, M., Taliani, G., Sarmati, L., Picciotto, A., Vullo, V., Caporaso, N., Paoloni, M., Pasquazzi, C., Rizzardini, G., Parruti, G., Craxã¬, A., Babudieri, S., Andreoni, M., Angelico, M., Perno, C., Ceccherini-Silberstein, F., Mariani, R., Iapadre, N., Grimaldi, A., Andreone, P., Menzaghi, B., Quirino, T., Pisani, V., Torti, C., Bruzzone, B., De Maria, A., Marenco, S., Nicolini, L., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, M., Aghemo, A., Boccaccio, V., Bruno, S., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Lleo, A., Mancon, A., Monico, S., Niero, F., Russo, M., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Gaeta, G., Lembo, V., Sangiovanni, V., DI MARCO, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pieri, A., Polilli, E., Sozio, F., Antenucci, F., Baiocchi, L., Biliotti, E., Biolato, M., Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Leonardis, F., De Sanctis, A., Di Paolo, D., Furlan, C., Gallo, P., Gasbarrini, A., Giannelli, V., Grieco, S., Lambiase, L., Lattanzi, B., Lula, R., Malagnino, V., Manuelli, M., Miglioresi, L., Milana, M., Moretti, A., Nosotti, L., Palazzo, D., Romano, M., Sarrecchia, C., Sforza, D., Sorbo, M., Spaziante, M., Svicher, V., Tisone, G., Vespasiani-Gentilucci, U., D'Adamo, G., Mangia, A., Maida, I., Mura, M., Falconi, L., Di Giammartino, D., Di Maio, V, Cento, V, Lenci, I, Aragri, M, Rossi, P, Barbaliscia, S, Melis, M, Verucchi, G, Magni, C, Teti, E, Bertoli, A, Antonucci, F, Bellocchi, M, Micheli, V, Masetti, C, Landonio, S, Francioso, S, Santopaolo, F, Pellicelli, A, Calvaruso, V, Gianserra, L, Siciliano, M, Romagnoli, D, Cozzolongo, R, Grieco, A, Morisco, F, Merli, M, Brancaccio, G, Di Biagio, A, Loggi, E, Mastroianni, C, Pace Palitti, V, Tarquini, P, Puoti, M, Taliani, G, Sarmati, L, Picciotto, A, Vullo, V, Caporaso, N, Paoloni, M, Pasquazzi, C, Rizzardini, G, Parruti, G, Craxì, A, Babudieri, S, Andreoni, M, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Velia C. Di Maio, Valeria Cento, Ilaria Lenci, Marianna Aragri, Piera Rossi, Silvia Barbaliscia, Michela Meli, Gabriella Verucchi, Carlo F. Magni, Elisabetta Teti, Ada Bertoli, Francesco Paolo Antonucci, Maria C. Bellocchi, Valeria Micheli, Chiara Masetti, Simona Landonio, Simona Francioso, Francesco Santopaolo, Adriano M. Pellicelli, Vincenza Calvaruso, Laura Gianserra, Massimo Siciliano, Dante Romagnoli, Raffaele Cozzolongo, Antonio Grieco, Jacopo Vecchiet, Filomena Morisco, Manuela Merli, Giuseppina Brancaccio, Antonio Di Biagio, Elisabetta Loggi, Claudio M. Mastroianni, Valeria Pace Palitti, Pierluigi Tarquini, Massimo Puoti, Gloria Taliani, Loredana Sarmati, Antonino Picciotto, Vincenzo Vullo, Nicola Caporaso, Maurizio Paoloni, Caterina Pasquazzi, Giuliano Rizzardini, Giustino Parruti, Antonio Craxì, Sergio Babudieri, Massimo Andreoni, Mario Angelico, Carlo F. Perno, Francesca Ceccherini-Silberstein, for the HCV Italian Resistance Network Study Group: [.., P. Andreone, E. Loggi, G. Verucchi, ], Di Maio, Velia C., Cento, Valeria, Lenci, Ilaria, Aragri, Marianna, Rossi, Piera, Barbaliscia, Silvia, Melis, Michela, Verucchi, Gabriella, Magni, Carlo F., Teti, Elisabetta, Bertoli, Ada, Antonucci, Francescopaolo, Bellocchi, Maria C., Micheli, Valeria, Masetti, Chiara, Landonio, Simona, Francioso, Simona, Santopaolo, Francesco, Pellicelli, Adriano M., Calvaruso, Vincenza, Gianserra, Laura, Siciliano, Massimo, Romagnoli, Dante, Cozzolongo, Raffaele, Grieco, Antonio, Vecchiet, Jacopo, Morisco, Filomena, Merli, Manuela, Brancaccio, Giuseppina, Di Biagio, Antonio, Loggi, Elisabetta, Mastroianni, Claudio M., Pace Palitti, Valeria, Tarquini, Pierluigi, Puoti, Massimo, Taliani, Gloria, Sarmati, Loredana, Picciotto, Antonino, Vullo, Vincenzo, Caporaso, Nicola, Paoloni, Maurizio, Pasquazzi, Caterina, Rizzardini, Giuliano, Parruti, Giustino, Craxã¬, Antonio, Babudieri, Sergio, Andreoni, Massimo, Angelico, Mario, Perno, Carlo F., Ceccherini-Silberstein, Francesca, Nicolini, L. A., Magni, C. F., Russo, M. L., Gaeta, G. B., Di Marco, V., Di Maio, V. C., Sorbo, M. C., Mura, M. S., Di Maio, Velia C, Magni, Carlo F, Bellocchi, Maria C, Pellicelli, Adriano M, Mastroianni, Claudio M, Craxì, Antonio, Perno, Carlo F, and Ceccherini Silberstein, Francesca

Subjects
Male, 0301 basic medicine, hepatitis C virus, Sustained Virologic Response, Sofosbuvir, Hepacivirus, Drug Resistance, resistance-associated substitutions, Viral Nonstructural Proteins, VARIANTS, NS5A, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, INFECTION, antiviral therapy, Medicine, hepatitis C viru, Viral, Treatment Failure, Chronic, direct-acting antivirals, resistance test, hepatology, biology, GENOTYPE 1, virus diseases, Middle Aged, Settore MED/07 - Microbiologia e Microbiologia Clinica, Hepatitis C, Italy, Combination, Interferon, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Author Keywords:antiviral therapy, RIBAVIRIN, Sequence Analysis, Human, medicine.drug, medicine.medical_specialty, Daclatasvir, Genotype, Hepatitis C virus, Antiviral Agents, LONG-TERM PERSISTENCE, DACLATASVIR, 03 medical and health sciences, Drug Therapy, Aged, Drug Resistance, Viral, Hepatitis C, Chronic, Humans, Interferons, Mutation, Ribavirin, Sequence Analysis, DNA, Hepatology, TREATMENT-NAIVE, Internal medicine, Antiviral Agent, resistance-associated substitution, direct-acting antiviral, Hepaciviru, resistance test KeyWords Plus:HEPATITIS-C VIRUS, business.industry, Viral Nonstructural Protein, DNA, biology.organism_classification, Clinical trial, 030104 developmental biology, SOFOSBUVIR, chemistry, Sequence Analysi, Immunology, business
Abstract

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.

Published
2017
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15. A meta-analysis of single HCV-untreated arm of studies evaluating outcomes after curative treatments of HCV-related hepatocellular carcinoma

Author

Cabibbo, Giuseppe, Petta, Salvatore, Barbã ra, Marco, Missale, Gabriele, Virdone, Roberto, Caturelli, Eugenio, Piscaglia, Fabio, Morisco, Filomena, Colecchia, Antonio, Farinati, Fabio, Giannini, Edoardo, Trevisani, Franco, Craxã¬, Antonio, Colombo, Massimo, Cammã , Calogero, Bucci, Laura, Zoli, Marco, Garuti, Francesca, Lenzi, Barbara, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Gramenzi, Annagiulia, Granito, Alessandro, Magalotti, Donatella, Serra, Carla, Negrini, Giulia, Napoli, Lucia, Salvatore, Veronica, Benevento, Francesca, Benvegnã¹, Luisa, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Ciccarese, Francesca, Del Poggio, Paolo, Olmi, Stefano, de Matthaeis, Nicoletta, Balsamo, Mariella Di Marco Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Attardo, Simona, Rossi, Margherita, Costantino, Andrea, Affronti, Andrea, Affronti, Marco, Mascari, Marta, Felder, Martina, Mega, Andrea, Gasbarrini, Antonio, Pompili, Maurizio, Rinninella, Emanuele, Sacco, Rodolfo, Mismas, Valeria, Foschi, Francesco Giuseppe, Dall’Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Olivani, Andrea, Biasini, Elisabetta, Nardone, Gerardo, Guarino, Maria, Svegliati-Baroni, Gialuca, Ortolani, Alessio, Masotto, Alberto, Marchetti, Fabiana, Valerio, Matteo, Marra, Fabio, Aburas, Sami, Inghilesi, Andrea L, Cappelli, Alberta, Golfieri, Rita, Mosconi, MARIA CRISTINA, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Benvegnu', Luisa, Cabibbo, Giuseppe, Petta, Salvatore, Barbàra, Marco, Missale, Gabriele, Virdone, Roberto, Caturelli, Eugenio, Piscaglia, Fabio, Morisco, Filomena, Colecchia, Antonio, Farinati, Fabio, Giannini, Edoardo, Trevisani, Franco, Craxì, Antonio, Colombo, Massimo, Cammà, Calogero, Nardone, GERARDO ANTONIO PIO, Cabibbo, G., Petta, S., Barbara, M., Missale, G., Virdone, R., Caturelli, E., Piscaglia, F., Morisco, F., Colecchia, A., Farinati, F., Giannini, E., Trevisani, F., Craxi, A., Colombo, M., Camma, C., Bucci, L., Zoli, M., Garuti, F., Lenzi, B., Biselli, M., Caraceni, P., Cucchetti, A., Gramenzi, A., Granito, A., Magalotti, D., Serra, C., Negrini, G., Napoli, L., Salvatore, V., Benevento, F., Benvegnu, L., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Moscatelli, A., Pellegatta, G., Picciotto, A., Savarino, V., Ciccarese, F., Del Poggio, P., Olmi, S., de Matthaeis, N., Balsamo, M. D. M. C., Vavassori, E., Roselli, P., Dell'Isola, S., Ialungo, A. M., Rastrelli, E., Attardo, S., Rossi, M., Costantino, A., Affronti, A., Affronti, M., Mascari, M., Felder, M., Mega, A., Gasbarrini, A., Pompili, M., Rinninella, E., Sacco, R., Mismas, V., Foschi, F. G., Dall'Aglio, A. C., Feletti, V., Lanzi, A., Cappa, F. M., Neri, E., Stefanini, G. F., Tamberi, S., Olivani, A., Biasini, E., Nardone, G., Guarino, M., Svegliati-Baroni, G., Ortolani, A., Masotto, A., Marchetti, F., Valerio, M., Marra, F., Aburas, S., Inghilesi, A. L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Coccoli, P., Zamparelli, M. S., Barbã ra, Marco, Craxã¬, Antonio, Cammã , Calogero, Bucci, Laura, Zoli, Marco, Garuti, Francesca, Lenzi, Barbara, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Gramenzi, Annagiulia, Granito, Alessandro, Magalotti, Donatella, Serra, Carla, Negrini, Giulia, Napoli, Lucia, Salvatore, Veronica, Benevento, Francesca, Benvegnã¹, Luisa, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Ciccarese, Francesca, Del Poggio, Paolo, Olmi, Stefano, de Matthaeis, Nicoletta, Balsamo, Mariella Di Marco Claudia, Vavassori, Elena, Roselli, Paola, Dellâ isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Attardo, Simona, Rossi, Margherita, Costantino, Andrea, Affronti, Andrea, Affronti, Marco, Mascari, Marta, Felder, Martina, Mega, Andrea, Gasbarrini, Antonio, Pompili, Maurizio, Rinninella, Emanuele, Sacco, Rodolfo, Mismas, Valeria, Foschi, Francesco Giuseppe, Dallâ aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Federica Mirici, Cappa, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Olivani, Andrea, Biasini, Elisabetta, Nardone, Gerardo, Guarino, Maria, Svegliati-Baroni, Gialuca, Ortolani, Alessio, Masotto, Alberto, Marchetti, Fabiana, Valerio, Matteo, Marra, Fabio, Aburas, Sami, Inghilesi, Andrea L, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Camma', C., Benvegnã¹, L., Balsamo, M., Dell’Isola, S., Ialungo, A., Foschi, F., Dall’Aglio, A., Cappa, F., Stefanini, G., Inghilesi, A., and Zamparelli, M.

Subjects
Oncology, medicine.medical_specialty, Carcinoma, Hepatocellular, recurrence, Hepatitis C virus, medicine.medical_treatment, medicine.disease_cause, survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Adjuvant therapy, hepatocellular carcinoma, prognosis, recurrences, Humans, Survival analysis, Hepatology, business.industry, Liver Neoplasms, medicine.disease, Hepatitis C, 030220 oncology & carcinogenesis, Meta-analysis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Neoplasm Recurrence, Local, business, Adjuvant, prognosi
Abstract

Background & Aims: Determining risk for recurrence or survival after curative resection or ablation in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is important for stratifying patients according to expected outcomes in future studies of adjuvant therapy in the era of direct-acting antivirals (DAAs). The aims of this meta-analysis were to estimate the recurrence and survival probabilities of HCV-related early HCC following complete response after potentially curative treatment and to identify predictors of recurrence and survival. Methods: Studies reporting time-dependent outcomes (HCC recurrence or death) after potentially curative treatment of HCV-related early HCC were identified in MEDLINE through May 2016. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of recurrence and survival. Results: Eleven studies met the inclusion criteria. Pooled estimates of actuarial recurrence rates were 7.4% at 6months and 47.0% at 2years. Pooled estimates of actuarial survival rates were 79.8% at 3years and 58.6% at 5years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, lower serum albumin, randomized controlled trial study design and follow-up were independently associated with higher recurrence risk, whereas tumour size and alpha-foetoprotein levels were associated with higher mortality. Conclusions: This meta-analysis showed that recurrence risk and survival are extremely variable in patients with successfully treated HCV-related HCC, providing a useful benchmark for indirect comparisons of the benefits of DAAs and for a correct design of randomized controlled trials in the adjuvant setting.

Published
2017

16. Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon

Author

Petta, S., Cabibbo, G., Barbara, M., Attardo, S., Bucci, L., Farinati, F., Giannini, E. G., Tovoli, F., Ciccarese, F., Rapaccini, Gian Ludovico, Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnù, L., Gasbarrini, Antonio, Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Nardone, G., Colecchia, A., Persico, M., Boccaccio, V., Craxì, A., Bruno, S., Trevisani, F., Cammà, C, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Piscaglia, Fabio, Gramenzi, Annagiulia, Granito, Alessandro, Magalotti, Donatella, Serra, Carla, Negrini, Giulia, Napoli, L., Napoli, Lucia, Salvatore, Veronica, Benevento, Francesca, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Delpoggio, Paolo, Olmi, Stefano, De Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Rini, Francesca, Costantino, Andrea, Affronti, Andrea, Affronti, Marco, Mascari, Marta, Mega, Andrea, Pompili, Maurizio, Rinninella, Emanuele, Mismas, Valeria, Dall’Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Missale, Gabriele, Guarino, Maria, Ortolani, Alessio, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Aburas, Sami, Inghilesi, Andrea L., Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Petta, Salvatore, Cabibbo, Giuseppe, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G., Tovoli, Francesco, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Dimarco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Persico, Marcello, Boccaccio, Vincenzo, Craxì, Antonio, Bruno, Savino, Trevisani, Franco, Cammà, Calogero, Petta, S, Cabibbo, G, Barbara, M, Attardo, S, Bucci, L, Farinati, F, Giannini, E. G, Tovoli, F, Ciccarese, F, Rapaccini, G. L, Di Marco, M, Caturelli, E, Zoli, M, Borzio, F, Sacco, R, Virdone, R, Marra, F, Felder, M, Morisco, Filomena, Benvegnù, L, Gasbarrini, A, Svegliati Baroni, G, Foschi, F. G, Olivani, A, Masotto, A, Nardone, GERARDO ANTONIO PIO, Colecchia, A, Persico, M, Boccaccio, V, Craxì, A, Bruno, S, Trevisani, F, Cammà, C., DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, Facolta' di MEDICINA e CHIRURGIA, Da definire, AREA MIN. 06 - Scienze mediche, Petta, S., Cabibbo, G., Barbara, M., Attardo, S., Bucci, L., Farinati, F., Giannini, E., Tovoli, F., Ciccarese, F., Rapaccini, G., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnã¹, L., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F., Olivani, A., Masotto, A., Nardone, G., Colecchia, A., Persico, M., Boccaccio, V., Craxi, A., Bruno, S., Trevisani, F., Camma', C., Biselli, M., Caraceni, P., Cucchetti, A., Domenicali, M., Piscaglia, F., Gramenzi, A., Granito, A., Magalotti, D., Serra, C., Negrini, G., Napoli, L., Salvatore, V., Benevento, F., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Moscatelli, A., Pellegatta, G., Picciotto, A., Savarino, V., Delpoggio, P., Olmi, S., Dematthaeis, N., Balsamo, C., Vavassori, E., Roselli, P., Dell’Isola, S., Ialungo, A., Rastrelli, E., Rini, F., Costantino, A., Affronti, A., Affronti, M., Mascari, M., Mega, A., Pompili, M., Rinninella, E., Mismas, V., Dall’Aglio, A., Feletti, V., Lanzi, A., Cappa, F., Neri, E., Stefanini, G., Tamberi, S., Biasini, E., Missale, G., Guarino, M., Ortolani, A., Chiaramonte, M., Marchetti, F., Valerio, M., Aburas, S., Inghilesi, A., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Coccoli, P., Zamparelli, M., Giannini, E.G., Rapaccini, G.L., Benvegnù, L., Foschi, F.G., Craxì, A., Cammà, C, the Italian Liver Cancer (ITALICA) Group [, Maurizio Biselli, Paolo Caraceni, Alessandro Cucchetti, Marco Domenicali, Fabio Piscaglia, Annagiulia Gramenzi, Alessandro Granito, Donatella Magalotti, Carla Serra, Giulia Negrini, Lucia Napoli, Veronica Salvatore, Francesca Benevento, ], Giannini, E. G., Rapaccini, G. L., Benvegnu, L., Foschi, F. G., Camma, C., Dell'Isola, S., Ialungo, A. M., Dall'Aglio, A. C., Cappa, F. M., Stefanini, G. F., Inghilesi, A. L., and Zamparelli, M. S.

Subjects
Liver Cirrhosis, Male, Cirrhosis, Databases, Factual, Gastroenterology, HCV-infected cirrhotic patients, hepatocellular carcinoma, HCC, sustained viral eradication, SVR, interferon, 0302 clinical medicine, Retrospective Studie, Pharmacology (medical), Prospective Studies, Prospective cohort study, Aged, 80 and over, Liver Neoplasms, virus diseases, Hepatitis C, Middle Aged, Liver Neoplasm, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Catheter Ablation, Interferon, 030211 gastroenterology & hepatology, Female, Liver cancer, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Liver Cirrhosi, Antiviral Agents, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Early Hepatocellular Carcinoma, Humans, Aged, Retrospective Studies, Antiviral Agent, Hepatology, business.industry, Settore MED/09 - MEDICINA INTERNA, Retrospective cohort study, medicine.disease, digestive system diseases, Surgery, Prospective Studie, Interferons, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

none 48 no Background: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. Aim: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. Methods: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. Results: TTR by Kaplan–Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. Conclusion: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used. Petta, S.; Cabibbo, G.; Barbara, M.; Attardo, S.; Bucci, L.; Farinati, F.; Giannini, E.G.; Tovoli, F.; Ciccarese, F.; Rapaccini, G.L.; Di Marco, M.; Caturelli, E.; Zoli, M.; Borzio, F.; Sacco, R.; Virdone, R.; Marra, F.; Felder, M.; Morisco, F.; Benvegnù, L.; Gasbarrini, A.; Svegliati-Baroni, G.; Foschi, F.G.; Olivani, A.; Masotto, A.; Nardone, G.; Colecchia, A.; Persico, M.; Boccaccio, V.; Craxì, A.; Bruno, S.; Trevisani, F.; Cammà, C; the Italian Liver Cancer (ITALICA) Group [ ; Maurizio Biselli; Paolo Caraceni; Alessandro Cucchetti; Marco Domenicali; Fabio Piscaglia; Annagiulia Gramenzi; Alessandro Granito; Donatella Magalotti; Carla Serra; Giulia Negrini; Lucia Napoli; Veronica Salvatore; Francesca Benevento;] Petta, S.; Cabibbo, G.; Barbara, M.; Attardo, S.; Bucci, L.; Farinati, F.; Giannini, E.G.; Tovoli, F.; Ciccarese, F.; Rapaccini, G.L.; Di Marco, M.; Caturelli, E.; Zoli, M.; Borzio, F.; Sacco, R.; Virdone, R.; Marra, F.; Felder, M.; Morisco, F.; Benvegnù, L.; Gasbarrini, A.; Svegliati-Baroni, G.; Foschi, F.G.; Olivani, A.; Masotto, A.; Nardone, G.; Colecchia, A.; Persico, M.; Boccaccio, V.; Craxì, A.; Bruno, S.; Trevisani, F.; Cammà, C; the Italian Liver Cancer (ITALICA) Group [ ; Maurizio Biselli; Paolo Caraceni; Alessandro Cucchetti; Marco Domenicali; Fabio Piscaglia; Annagiulia Gramenzi; Alessandro Granito; Donatella Magalotti; Carla Serra; Giulia Negrini; Lucia Napoli; Veronica Salvatore; Francesca Benevento;]

Published
2017

17. AISF position paper on liver disease and pregnancy

Author

Morisco, Filomena, Bruno, Raffaele, Bugianesi, Elisabetta, Burra, Patrizia, Calvaruso, Vincenza, Cannoni, Alice, Caporaso, Nicola, Caviglia, Gian Paolo, Ciancio, Alessia, Fargion, Silvia, Federico, Alessandro, Floreani, Annarosa, Gaeta, Giovanni Battista, Guarino, Maria, Invernizzi, Pietro, Licata, Anna, Loguercio, Carmela, Mazzella, Giuseppe, Petraglia, Felice, Primignani, Massimo, Rodriguez Castro, Kryssia, Smedile, Antonina, Valenti, Luca, Vanni, Ester, Vannuccini, Silvia, Voltolini, Chiara, Villa, Erica, Italian Assoc Study Liver, Aisf, Morisco, F, Bruno, R, Bugianesi, E, Burra, P, Calvaruso, V, Cannoni, A, Caporaso, N, Caviglia, GP, Ciancio, A, Fargion, S, Federico, A, Floreani, A, Gaeta, GB, Guarino, M, Invernizzi, P, Licata, A, Loguercio, C, Mazzella, G, Petraglia, F, Primignani, M, Rodriguez-Castro, K, Smedile, A, Valenti, L, Vanni, E, Vannuccini, S, Voltolini, C, Villa, E, Morisco, Filomena, Bruno, Raffaele, Bugianesi, Elisabetta, Burra, Patrizia, Calvaruso, Vincenza, Cannoni, Alice, Caporaso, Nicola, Caviglia, Gian Paolo, Ciancio, Alessia, Fargion, Silvia, Federico, Alessandro, Floreani, Annarosa, Gaeta, Giovanni Battista, Guarino, Maria, Invernizzi, Pietro, Licata, Anna, Loguercio, Carmela, Mazzella, Giuseppe, Petraglia, Felice, Primignani, Massimo, Rodriguez-castro, Kryssia, Smedile, Antonina, Valenti, Luca, Vannic, Ester, Vannuccini, Silvia, Voltolini, Chiara, Villao, Erica, Rodriguez Castro, Kryssia, Vanni, Ester, Villa, Erica, Caviglia, G, Gaeta, G, Rodriguez Castro, K, Caviglia, Gp, Loguercio, Carmelina, and Villa, E. 1. 6.

Subjects
Cholagogues and Choleretics, Viral Hepatitis, Budd-Chiari Syndrome, Chronic liver disease, Adrenal Cortex Hormone, Gastroenterology, Hyperemesis gravidarum, Liver disease, 0302 clinical medicine, Pre-Eclampsia, Adrenal Cortex Hormones, Cholelithiasis, MED/12 - GASTROENTEROLOGIA, Pregnancy, Hyperemesis Gravidarum, Eclampsia, Cholelithiasi, Thiamine, Pregnancy Complications, Infectious, Cholagogues and Choleretic, Societies, Medical, 030219 obstetrics & reproductive medicine, Fatty liver, Ursodeoxycholic Acid, Calcium Channel Blockers, Liver diseases, Hepatology, Pregnancy Complication, Antihypertensive Agent, Italy, Vitamin B Complex, Budd–Chiari syndrome, 030211 gastroenterology & hepatology, Female, Calcium Channel Blocker, Human, Viral Hepatitis Vaccines, medicine.medical_specialty, HELLP Syndrome, Hepatitis, Viral, Human, HELLP syndrome, Cholestasis, Intrahepatic, 03 medical and health sciences, Magnesium Sulfate, Internal medicine, medicine, Humans, Intensive care medicine, Antihypertensive Agents, business.industry, medicine.disease, Pregnancy Complications, Fatty Liver, Pregnancy, Liver disease, Viral Hepatitis, Pregnancy Complications, Infectiou, Fluid Therapy, business, Viral Hepatitis Vaccine
Abstract

The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disease occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and an assessment of the available treatment options. The report contains in three sections: (1) specific liver diseases of pregnancy; (2) liver disease occurring during pregnancy; and (3) pregnancy in patients with pre-existing chronic liver disease. Each topic is discussed considering the most relevant data available in literature; the final statements are formulated according to both scientific evidence and clinical expertise of the involved physicians, and the AISF expert panel recommendations are reported.

Published
2016

18. Application of the Intermediate-Stage Subclassification to Patients With Untreated Hepatocellular Carcinoma

Author

Giannini, Edoardo G, Moscatelli, Alessandro, Pellegatta, Gaia, Vitale, Alessandro, Farinati, Fabio, Ciccarese, Francesca, Piscaglia, Fabio, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Cabibbo, Giuseppe, Felder, Martina, Sacco, Rodolfo, Morisco, Filomena, Missale, Gabriele, Foschi, Francesco Giuseppe, Gasbarrini, Antonio, Baroni, Gianluca Svegliati, Virdone, Roberto, Masotto, Alberto, Trevisani, Franco, Bolondi, Luigi, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Pecorelli, Anna, Serra, Carla, Venerandi, Laura, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Del Poggio, Paolo, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnu', Luisa, Capelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Bosco, Giulia, Roselli, Paola, Dell'Isola, Serena, Maria Ialungo, Anna, Rastrelli, Elena, Picciotto, Antonino, Savarino, Vincenzo, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, Lanzi, Arianna, Cappa, Federica Mirici, Musetto, Alessandro, Neri, Elga, Stefanini, Giuseppe Francesco, Suzzi, Alessandra, Tamberi, Stefano, Triossi, Omero, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Giannini, Edoardo G, Moscatelli, Alessandro, Pellegatta, Gaia, Vitale, Alessandro, Farinati, Fabio, Ciccarese, Francesca, Piscaglia, Fabio, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Cabibbo, Giuseppe, Felder, Martina, Sacco, Rodolfo, Morisco, Filomena, Missale, Gabriele, Foschi, Francesco Giuseppe, Gasbarrini, Antonio, Baroni, Gianluca Svegliati, Virdone, Roberto, Masotto, Alberto, Trevisani, Franco, Bolondi, Luigi, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Pecorelli, Anna, Serra, Carla, Venerandi, Laura, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Del Poggio, Paolo, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnù, Luisa, Capelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Bosco, Giulia, Roselli, Paola, Dell'Isola, Serena, Maria Ialungo, Anna, Rastrelli, Elena, Picciotto, Antonino, Savarino, Vincenzo, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, Lanzi, Arianna, Cappa, Federica Mirici, Musetto, Alessandro, Neri, Elga, Stefanini, Giuseppe Francesco, Suzzi, Alessandra, Tamberi, Stefano, Triossi, Omero, Chiaramonte, Maria, Marchetti, Fabiana, and Valerio, Matteo

Subjects
Adult, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Prognosi, Aged, Aged, 80 and over, Female, Humans, Liver Neoplasms, Middle Aged, Neoplasm Staging, Prognosis, Prospective Studies, Young Adult, Gastroenterology, Intermediate stage, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Carcinoma, 80 and over, Prospective cohort study, Hepatology, business.industry, Medicine (all), Settore MED/09 - MEDICINA INTERNA, Hepatocellular, medicine.disease, Prospective Studie, Liver Neoplasm, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Neoplasm staging, Liver cancer, business, Human
Abstract

OBJECTIVES:The Barcelona Clinic Liver Cancer (BCLC) intermediate stage (BCLC B) includes a heterogeneous population of patients with hepatocellular carcinoma (HCC). Recently, in order to facilitate treatment decisions, a panel of experts proposed to subclassify BCLC B patients. In this study, we aimed to assess the prognostic capability of the BCLC B stage reclassification in a large cohort of patients with untreated HCC managed by the Italian Liver Cancer Group.METHODS:We assessed the prognosis of 269 untreated HCC patients observed in the period 1987-2012 who were reclassified according to the proposed subclassification of the BCLC B stage from stage B1 to stage B4. We evaluated and compared the survival of the various substages.RESULTS:Median survival progressively decreased from stage B1 (n=65, 24.2%: 25 months) through stages B2 (n=105, 39.0%: 16 months) and B3 (n=22, 8.2%: 9 months), to stage B4 (n=77, 28.6%: 5 months; P

Published
2016

19. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study

Author

Piscaglia, Fabio, Svegliati Baroni, Gianluca, Barchetti, Andrea, Pecorelli, Anna, Marinelli, Sara, Tiribelli, Claudio, Bellentani, Stefano, Bernardi M, Biselli M, Bernardi M, Biselli M, Caraceni P, Domenicali M, Garuti F, Gramenzi A, Lenzi B, Magalotti D, Cescon M, Ravaioli M, Del Poggio P, Olmi S, Rapaccini GL, Balsamo C, Di Nolfo MA, Vavassori E, Alberti A, Benvegnù L, Gatta A, Giacomin A, Vanin V, Pozzan C, Maddalo G, Giampalma E, Cappelli A, Golfieri R, Mosconi C, Renzulli M, Roselli P, Dell'Isola S, Ialungo AM, Risso D, Marenco S, Sammito G, Bruzzone L, Bosco G, Grieco A, Pompili M, Rinninella E, Siciliano M, Chiaramonte M, Guarino M, Cammà C, Maida M, Costantino A, Barcellona MR, Schiadà L, Gemini S, Lanzi A, Stefanini GF, Dall'Aglio AC, Cappa FM, Suzzi A, Mussetto A, Treossi O, Missale G, Porro E, Mismas V, Vivaldi C, Bolondi L, Zoli M, Granito A, Malagotti D, Tovoli F, Trevisani F, Venerandi L, Brandi G, Cucchetti A, Bugianesi E, Vanni E, Mezzabotta L, Cabibbo G, Petta S, Fracanzani A, Fargion S, Marra F, Fani B, Biasini E, Sacco R, CAPORASO, NICOLA, Colombo M, D'Ambrosio R, Crocè LS, Patti R, Giannini EG, Loria P, Lonardo A, Baldelli E, Miele L, Farinati F, Borzio M, Dionigi E, Soardo G, Caturelli E, Ciccarese F, Virdone R, Affronti A, Foschi FG, Borzio F., MORISCO, FILOMENA, Piscaglia, Fabio, Svegliati Baroni, Gianluca, Barchetti, Andrea, Pecorelli, Anna, Marinelli, Sara, Tiribelli, Claudio, Bellentani, Stefano, Bernardi M, Biselli M, Bernardi, M, Biselli, M, Caraceni, P, Domenicali, M, Garuti, F, Gramenzi, A, Lenzi, B, Magalotti, D, Cescon, M, Ravaioli, M, Del Poggio, P, Olmi, S, Rapaccini, Gl, Balsamo, C, Di Nolfo, Ma, Vavassori, E, Alberti, A, Benvegnù, L, Gatta, A, Giacomin, A, Vanin, V, Pozzan, C, Maddalo, G, Giampalma, E, Cappelli, A, Golfieri, R, Mosconi, C, Renzulli, M, Roselli, P, Dell'Isola, S, Ialungo, Am, Risso, D, Marenco, S, Sammito, G, Bruzzone, L, Bosco, G, Grieco, A, Pompili, M, Rinninella, E, Siciliano, M, Chiaramonte, M, Guarino, M, Cammà, C, Maida, M, Costantino, A, Barcellona, Mr, Schiadà, L, Gemini, S, Lanzi, A, Stefanini, Gf, Dall'Aglio, Ac, Cappa, Fm, Suzzi, A, Mussetto, A, Treossi, O, Missale, G, Porro, E, Mismas, V, Vivaldi, C, Bolondi, L, Zoli, M, Granito, A, Malagotti, D, Tovoli, F, Trevisani, F, Venerandi, L, Brandi, G, Cucchetti, A, Bugianesi, E, Vanni, E, Mezzabotta, L, Cabibbo, G, Petta, S, Fracanzani, A, Fargion, S, Marra, F, Fani, B, Biasini, E, Sacco, R, Morisco, Filomena, Caporaso, Nicola, Colombo, M, D'Ambrosio, R, Crocè, L, Patti, R, Giannini, Eg, Loria, P, Lonardo, A, Baldelli, E, Miele, L, Farinati, F, Borzio, M, Dionigi, E, Soardo, G, Caturelli, E, Ciccarese, F, Virdone, R, Affronti, A, Foschi, Fg, Borzio, F., Fabio Piscagliaxxx, Gianluca Svegliati-Baroni, Andrea Barchetti, Anna Pecorellixxx, Sara Marinellixxx, Claudio Tiribelli, and, Stefano Bellentani, on behalf of the HCC-NAFLD Italian Study Group [, Mauro Bernardi, Maurizio Biselli, Paolo Caraceni, Marco Domenicali, Francesca Garuti, Annagiulia Gramenzi, Barbara Lenzi, Donatella Magalotti, Matteo Cescon, Matteo Ravaioli, Emanuela Giampalma, Rita Golfieri, Cristina Mosconi, Luigi Bolondi, Marco Zoli, Alessandro Granito, Francesco Tovoli, Franco Trevisani, Laura Venerandi, Giovanni Brandi, Alessandro Cucchetti, ], DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, Facolta' di MEDICINA e CHIRURGIA, AREA MIN. 06 - Scienze mediche, Da definire, Croce', Saveria, and HCC NAFLD Italian Study, Group

Subjects
Male, Cirrhosis, Survival, Chronic liver disease, Gastroenterology, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, 80 and over, Prospective Studies, Chronic, Prospective cohort study, Aged, 80 and over, Medicine (all), Liver Neoplasms, hepatocellular carcinoma, Middle Aged, Hepatitis C, Liver Neoplasm, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Competing risk analysi, 030211 gastroenterology & hepatology, Female, Non Alcoholic SteatoHepatitis=NASH, Human, medicine.medical_specialty, Aged, Carcinoma, Hepatocellular, Hepatitis C, Chronic, Humans, Hepatology, Competing risk analysis, Milan criteria, 03 medical and health sciences, Internal medicine, medicine, Survival rate, business.industry, Settore MED/09 - MEDICINA INTERNA, Carcinoma, nutritional and metabolic diseases, Hepatocellular, medicine.disease, digestive system diseases, Nonalcoholic fatty liver disease, hepatocellular carcinoma, clinical patterns, business, clinical patterns
Abstract

none 31 no Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) CONCLUSIONS: NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment. Fabio Piscagliaxxx; Gianluca Svegliati-Baroni; Andrea Barchetti; Anna Pecorellixxx; Sara Marinellixxx; Claudio Tiribelli; and; Stefano Bellentani; on behalf of the HCC-NAFLD Italian Study Group [;Mauro Bernardi; Maurizio Biselli; Paolo Caraceni; Marco Domenicali; Francesca Garuti; Annagiulia Gramenzi; Barbara Lenzi; Donatella Magalotti; Matteo Cescon; Matteo Ravaioli; Emanuela Giampalma; Rita Golfieri; Cristina Mosconi; Luigi Bolondi; Marco Zoli; Alessandro Granito; Francesco Tovoli; Franco Trevisani; Laura Venerandi; Giovanni Brandi; Alessandro Cucchetti;] Fabio Piscagliaxxx; Gianluca Svegliati-Baroni; Andrea Barchetti; Anna Pecorellixxx; Sara Marinellixxx; Claudio Tiribelli; and; Stefano Bellentani; on behalf of the HCC-NAFLD Italian Study Group [;Mauro Bernardi; Maurizio Biselli; Paolo Caraceni; Marco Domenicali; Francesca Garuti; Annagiulia Gramenzi; Barbara Lenzi; Donatella Magalotti; Matteo Cescon; Matteo Ravaioli; Emanuela Giampalma; Rita Golfieri; Cristina Mosconi; Luigi Bolondi; Marco Zoli; Alessandro Granito; Francesco Tovoli; Franco Trevisani; Laura Venerandi; Giovanni Brandi; Alessandro Cucchetti;]

Published
2016

20. Long-term safety of anti-TNF-α in PsA patients with concomitant HCV infection: a retrospective observational multicenter study on 15 patients

Author

Costa L, Caso F, Atteno M, Giannitti C, Spadaro A, Ramonda R, Vezz? M, Fiocco U, Galeazzi M, Punzi L, SCARPA, RAFFAELE, COSTA, LUISA, DEL PUENTE, ANTONIO, MORISCO, FILOMENA, Costa, L, Caso, F, Atteno, M, Giannitti, C, Spadaro, A, Ramonda, R, Vezz?, M, DEL PUENTE, Antonio, Morisco, Filomena, Fiocco, U, Galeazzi, M, Punzi, L, Scarpa, Raffaele, Costa, Luisa, Caso, Francesco, Atteno, Mariangela, Giannitti, Chiara, Spadaro, Antonio, Ramonda, Roberta, Vezzù, Maristella, Del Puente, Antonio, Fiocco, Ugo, Galeazzi, Mauro, and Punzi, Leonardo

Subjects
Male, Time Factors, Inflammatory arthritis, Arthritis, medicine.disease_cause, Gastroenterology, Receptors, Tumor Necrosis Factor, Etanercept, Retrospective Studie, Antirheumatic Agent, Anti-TNF-α, Alanine Transaminase, General Medicine, Middle Aged, Viral Load, Hepatitis C, HCV infection, Antirheumatic Agents, Biological Product, Female, Viral load, Human, medicine.drug, medicine.medical_specialty, Time Factor, Hepatitis C virus, Antibodies, Monoclonal, Humanized, Psoriatic arthritis, Rheumatology, Internal medicine, medicine, Adalimumab, Humans, Aspartate Aminotransferases, Aged, Retrospective Studies, Inflammation, Biological Products, Tumor Necrosis Factor-alpha, business.industry, Psoriatic arthriti, Arthritis, Psoriatic, Aspartate Aminotransferase, medicine.disease, Immunoglobulin G, Concomitant, Immunology, business
Abstract

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α, in addition to its pro-inflammatory role, is an essential cytokine for the host's defense, and its depletion by treatment may facilitate the risk of viral infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in PsA patients with concurrent hepatitis C virus (HCV) infection. This is a multicenter study carried out in four Italian centers specialized in the diagnosis and treatment of PsA. At baseline and after 6 (T6) and 12 months (T12) of therapy, data concerning PsA activity and liver tests were registered. A total of 15 PsA patients with concomitant HCV infection were included in the study. At baseline, 13 patients had low viral load, and liver enzyme tests were within the normal range. During the observation period, these values remained stable. On the other hand, at baseline, a high viral load with slightly increased values of AST and ALT was detected in one patient. At T6 and T12, these values decreased. The remaining patient, at baseline, had low viral load, but with slightly increased AST and ALT values that normalized during the observation period. This is the greatest sample size available in the literature on this topic. The data suggests that anti-TNF-α agents are effective and safe in PsA patients with concomitant HCV. We suggest that the use of anti-TNF-α agents, accompanied by close monitoring, could be a therapeutic option.

Published
2014

21. Correlation between LDH levels and response to sorafenib in HCC patients: an analysis of the ITA.LI.CA database

Author

Sacco, Rodolfo, Mismas, Valeria, Granito, Alessandro, Musettini, Gianna, Masi, Gianluca, Caparello, Chiara, Vivaldi, Caterina, Felder, Martina, Bresci, Giampaolo, Fornaro, Lorenzo, Trevisani, Franco, Bernardi, Mauro, Bolondi, Luigi, Piscaglia, Fabio, Zoli, Marco, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Frigerio, Marta, Erroi, Virginia, Garuti, Francesca, Gramenzi, Annagiulia, Lenzi, Barbara, Magalotti, Donatella, Pecorelli, Anna, Venerandi, Laura, Farinati, Fabio, Giacomin, Anna, Vanin, Veronica, Pozzan, Caterina, Maddalo, Gemma, Ciccarese, Francesca, Del Poggio, Paolo, Olmi, Stefano, Di Marco, Mariella, Balsamo, Claudia, Di Nolfo, Maria Anna, Vavassori, Elena, Alberti, Alfredo, Benvegnã¹, Luisa, Gatta, Angelo, Gios, Maurizio, Golfieri, Rita, Giampalma, Emanuela, Mosconi, Cristina, Renzulli, Matteo, Rapaccini, Gian Lodovico, Bosco, Giulia, Caturelli, Eugenio, Roselli, Paola, Dell’isola, Serena, Ialungo, Anna Maria, Giannini, Edoardo G., Risso, Domenico, Marenco, Simona, Bruzzone, Linda, Savarino, Vincenzo, Picciotto, Antonino, Chiaramonte, Maria, Cabibbo, Giuseppe, Cammã , Calogero, Maida, Marcello, Di Martino, Arezia, Barcellona, Maria Rosa, Mega, Andrea, Gasbarrini, Antonio, Rinninella, Emanuele, Rotella, Virginia, Ginanni, Barbara, Foschi, Francesco Giuseppe, Lanzi, Arianna, Stefanini, Giuseppe Francesco, Dall’aglio, Anna Chiara, Cappa, Federica Mirici, Neri, Elga, Bassi, Paolo, Zanotti, Miriam, Missale, Gabriele, Biasini, Elisabetta, Porro, Emanuela, Morisco, Filomena, Guarino, Maria, Baroni, Gianluca Svegliati, Schiadã , Laura, Gemini, Stefano, Borzio, Francesco, Virdone, Roberto, Rodolfo Sacco, Valeria Misma, Alessandro Granito, Gianna Musettini, Gianluca Masi, Chiara Caparello, Caterina Vivaldi, Martina Felder, Giampaolo Bresci, Lorenzo Fornaro, for the Italian Liver Cancer (ITA.LI.CA) group: [.., Franco Trevisani, Mauro Bernardi, Luigi Bolondi, Fabio Piscaglia, Marco Zoli, Maurizio Biselli, Paolo Caraceni, Alessandro Cucchetti, Marco Domenicali, Marta Frigerio, Virginia Erroi, Francesca Garuti, Annagiulia Gramenzi, Barbara Lenzi, Donatella Magalotti, Anna Pecorelli, Laura Venerandi, Rita Golfieri, Emanuela Giampalma, Cristina Mosconi, Matteo Renzulli, and ]

Subjects
Oncology, Male, Pathology, Cancer Research, Clinical Biochemistry, Drug Resistance, L-Lactate dehydrogenase, Biomarkers, HCC, LDH, Sorafenib, Aged, Antineoplastic Agents, Biomarkers, Tumor, Carcinoma, Hepatocellular, Drug Resistance, Neoplasm, Female, Humans, Kaplan-Meier Estimate, L-Lactate Dehydrogenase, Liver Neoplasms, Middle Aged, Niacinamide, Phenylurea Compounds, ROC Curve, Retrospective Studies, Treatment Outcome, 2734, Antineoplastic Agent, Retrospective Studie, Neoplasm, Tumor, Liver Neoplasm, Hepatocellular carcinoma, Human, medicine.drug, Phenylurea Compound, medicine.medical_specialty, Sorafenib treatment, Pathology and Forensic Medicine, Text mining, Internal medicine, medicine, Carcinoma, neoplasms, business.industry, Retrospective cohort study, Hepatocellular, Biomarker, medicine.disease, digestive system diseases, business
Abstract

Background Lactate dehydrogenase (LDH) is a predictor of clinical outcome in hepatocellular carcinoma (HCC) patients. However, its predictive role in the clinical outcomes of sorafenib treatment has been poorly documented. The correlation between LDH levels and clinical outcomes in HCC patients treated with sorafenib and included in the nationwide Italian database ITA.LI.CA was investigated here. Patients and Methods The ITA.LI.CA database contains data for 5,136 HCC patients. All patients treated with sorafenib treatment and with available LDH values were considered. Overall survival (OS) and time to progression (TTP) were compared in patients with LDH levels above and below a defined threshold, determined through an ROC analysis. An explorative analysis investigated the relationship between the variation of LDH levels during treatment and response to sorafenib. Results Baseline LDH levels were available for 97 patients. The most accurate cutoff value for LDH concentration was 297 U/L. Patients with LDH values above (n=45) and below (n=52) this threshold showed equal OS (12.0 months) and TTP (4.0 months) values. Data on LDH levels during sorafenib treatment were reported for 10 patients. LDH values decreased in 3 patients (mean difference = -219 U/L) who also reported a prolonged OS and TTP versus those with unmodified/increased LDH (OS: NE (not evaluated) vs. 8.0 months, p=0.0083; TTP: 19.0 vs. 3.0 months, p=0.008). Conclusions The clinical benefits of sorafenib do not seem to be influenced by baseline LDH. According to the results of an explorative analysis, however, a decreased LDH concentration during sorafenib might be associated with improved clinical outcomes.

Published
2015

22. Incidence of HCC recurrence after DAA treatment for HCV in a multicentre Italian cohort study

Author

Nicola Caporaso, Angelo Salomone Megna, Maria Guarino, Filomena Morisco, Nicola Coppola, Federica Morando, Marco Guarracino, Anna Sessa, Luca Rinaldi, Andrea Aglitti, Dario Bruzzese, Giovan Giuseppe Di Costanzo, Guarino, Maria, Giuseppe Di Costanzo, Giovan, Bruzzese, Dario, Sessa, Anna, Guarracino, Marco, Rinaldi, Luca, Aglitti, Andrea, Salomone Megna, Angelo, Morando, Federica, Coppola, Nicola, Caporaso, Nicola, and Morisco, Filomena

Subjects
medicine.medical_specialty, Complementary and alternative medicine, business.industry, Internal medicine, Incidence (epidemiology), medicine, Pharmaceutical Science, Pharmacology (medical), medicine.disease, business, Obesity, Cohort study
Published
2020
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23. Surveillance for hepatocellular carcinoma with a 3-months interval in 'extremely high-risk' patients does not further improve survival

Author

Filippo Pelizzaro, Giulia Peserico, Marco D'Elia, Nora Cazzagon, Francesco Paolo Russo, Alessandro Vitale, Edoardo G. Giannini, Manuela Piccinnu, Gian Ludovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Rodolfo Sacco, Giuseppe Cabibbo, Fabio Marra, Andrea Mega, Filomena Morisco, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Gerardo Nardone, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Filippo Oliveri, Franco Trevisani, Fabio Farinati, Maurizio Biselli, Paolo Caraceni, Francesca Garuti, Annagiulia Gramenzi, Andrea Neri, Valentina Santi, Fabio Piscaglia, Francesco Tovoli, Alessandro Granito, Luca Muratori, Francesca Benevento, Elton Dajti, Giovanni Marasco, Federico Ravaioli, Alberta Cappelli, Rita Golfieri, Cristina Mosconi, Matteo Renzulli, Angela Imondi, Anna Sartori, Barbara Penzo, Elisa Pinto, Ester Marina Cela, Antonio Facciorusso, Valentina Cacciato, Edoardo Casagrande, Alessandro Moscatelli, Gaia Pellegatta, Nicoletta De Matthaeis, Gloria Allegrini, Valentina Lauria, Giorgia Ghittoni, Giorgio Pelecca, Fabrizio Chegai, Fabio Coratella, Mariano Ortenzi, Gabriele Missale, Alessandro Inno, Fabiana Marchetti, Anita Busacca, Calogero Cammà, Vincenzo Di Martino, Giacomo Emanuele Maria Rizzo, Maria Stella Franzè, Carlo Saitta, Assunta Sauchella, Vittoria Bevilacqua, Alberto Borghi, Andrea Casadei Gardini, Fabio Conti, Anna Chiara Dall'aglio, Giorgio Ercolani, Federica Mirici, Claudia Campani, Chiara Di Bonaventura, Stefano Gitto, Pietro Coccoli, Antonio Malerba, Maria Guarino, Maurizia Brunetto, Veronica Romagnoli, Pelizzaro, F., Peserico, G., D'Elia, M., Cazzagon, N., Russo, F. P., Vitale, A., Giannini, E. G., Piccinnu, M., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Marra, F., Mega, A., Morisco, F., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., Trevisani, F., Farinati, F., Biselli, M., Caraceni, P., Garuti, F., Gramenzi, A., Neri, A., Santi, V., Piscaglia, F., Tovoli, F., Granito, A., Muratori, L., Benevento, F., Dajti, E., Marasco, G., Ravaioli, F., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Imondi, A., Sartori, A., Penzo, B., Pinto, E., Cela, E. M., Facciorusso, A., Cacciato, V., Casagrande, E., Moscatelli, A., Pellegatta, G., De Matthaeis, N., Allegrini, G., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Missale, G., Inno, A., Marchetti, F., Busacca, A., Camma, C., Di Martino, V., Rizzo, G. E. M., Franze, M. S., Saitta, C., Sauchella, A., Bevilacqua, V., Borghi, A., Casadei Gardini, A., Conti, F., Dall'Aglio, A. C., Ercolani, G., Mirici, F., Campani, C., Di Bonaventura, C., Gitto, S., Coccoli, P., Malerba, A., Guarino, M., Brunetto, M., Romagnoli, V., Pelizzaro, Filippo, Peserico, Giulia, D'Elia, Marco, Cazzagon, Nora, Russo, Francesco Paolo, Vitale, Alessandro, Giannini, Edoardo G., Piccinnu, Manuela, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Oliveri, Filippo, Trevisani, Franco, Farinati, Fabio, Biselli, Maurizio, Caraceni, Paolo, Garuti, Francesca, Gramenzi, Annagiulia, Neri, Andrea, Santi, Valentina, Piscaglia, Fabio, Tovoli, Francesco, Granito, Alessandro, Muratori, Luca, Benevento, Francesca, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Imondi, Angela, Sartori, Anna, Penzo, Barbara, Pinto, Elisa, Cela, Ester Marina, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, Moscatelli, Alessandro, Pellegatta, Gaia, De Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Missale, Gabriele, Inno, Alessandro, Marchetti, Fabiana, Busacca, Anita, Cammà, Calogero, Di Martino, Vincenzo, Rizzo, Giacomo Emanuele Maria, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Bevilacqua, Vittoria, Borghi, Alberto, Casadei Gardini, Andrea, Conti, Fabio, Dall'aglio, Anna Chiara, Ercolani, Giorgio, Mirici, Federica, Campani, Claudia, Di Bonaventura, Chiara, Gitto, Stefano, Coccoli, Pietro, Malerba, Antonio, Guarino, Maria, Brunetto, Maurizia, and Romagnoli, Veronica

Subjects
medicine.medical_specialty, Carcinoma, Hepatocellular, Survival, Hepatocellular carcinoma, Cancer stage, Surveillance interval, Internal medicine, medicine, Humans, Propensity Score, Survival analysis, High risk patients, Hepatology, business.industry, Liver Neoplasms, Settore MED/09 - MEDICINA INTERNA, Gastroenterology, Patient survival, medicine.disease, Survival Analysis, Propensity score matching, Survival Analysi, Liver cancer, business, Median survival, Human
Abstract

Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9–64.0]) was not significantly different from the observed (47.0 months [35.0–58.9]; p = 0.43) and adjusted (44.9 months [33.4–56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. Conclusions A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics.

Published
2022

24. Acute Delta Hepatitis in Italy spanning three decades (1991-2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Author

Tommaso, Stroffolini, Filomena, Morisco, Luigina, Ferrigno, Giuseppina, Pontillo, Giuseppina, Iantosca, Valentina, Cossiga, Simonetta, Crateri, Maria Elena Tosti, Valeria, Alfonsi, Franca, D'Angelo, Zotti, Carla Maria, Rainero, Erika, Marengo, Noemi, Silvana, Malaspina, Angela, Gallone, Annalisa, Castella, Maria Teresa Galati, Annamaria, Scala, Paolo, Castagna, Virginia, Silano, Sebastiano, D'Agosta, Maria Grazia Tacca, Silvia, Iodice, Vilma, Corvi, Maurizio, Oddone, Daniela, Rivetti, Paola, Ravaschietto, Franco, Giovanetti, Teresa, Cappello, Alessandro, Smaniotto, Mario, Ruffier, Marina, Verardo, Maria, Gramegna, Sabrina, Senatore, Danilo, Cereda, Annalisa, Donadini, Carla, Nespoli, Livia, Trezzi, Giorgio, Gennati, Angelo, Monteverdi, Liana, Boldori, Franco Paolo Tortorella, Paola Elvira Merlini, Davide Di Caterina, Marino, Faccini, Anna, Lamberti, Eva, Rossetti, Rita, Brugnoli, Giulia, Mainardi, Alessandra, Vezzoli, Daniela, Caso, Milena, Testa, Alice, Erba, Paola, Senegaglia, Annamaria, Spagna, Silvia, Lodola, Marcello, Tirani, Enza, Giompapa, Luigi Guido Roveri, Gabriele, Guardigli, Vanna, Scalvinoni, Silvia, Spertini, Sabine, Gamper, Andrea, Grünfelder, Barbara, Ploner, Verena, Runggatscher, Silvia, Molinaro, Maria Grazia Zuccali, Silvia, Franchini, Francesca, Russo, Francesca, Zanella, Donatella, Rizzato, Graziella, Carpene, Nadia, Lamonato, Emanuela, Destefani, Alessandra Dal Zotto, Rita Dal Zotto, Paola, Casagrande, Felice, Foglia, Gemma, Zorzi, Ester, Chermaz, Liana, Gava, Luigi, Nicolardi, Lorena, Pavanetto, Cecilia, Battiston, Francesco De Grandi, Laura, Rizzato, Michele, Tonon, Elisabetta, Cannizzo, Maurizio, Foroni, Laura, Colucci, Monica, Barbieri, Rosanna, Ledri, Tolinda, Gallo, Giulio, Rocco, Rossana, Stacul, Ariella, Breda, Andrea, Iob, Simonetta, Micossi, Oriana, Feltrin, Giuseppina, Caernelos, Marco, Mela, Virna, Frumento, Anna, Opisso, Alessandro, Cuccu, Giorgio, Zoppi, Patrizia, Torracca, Armanda, Capellini, Francesco, Maddalo, Giovanna, Mattei, Claudio, Gualanduzzi, Erika, Massimiliani, Anna Rita Sacchi, Laura, Gardenghi, Anna Rosa Gianninoni, Elena Dalle Donne, Roberto, Rangoni, Annalisa, Califano, Chiara, Reali, Emilia, Biguzzi, Barbara, Bondi, Anna, Pecci, Bianca Maria Borrini, Lucia, Pecori, Emanuela, Balocchini, Costanza, Pierozzi, Rosa, Luzzoli, Paola, Marchini, Lara, Lucchesi, Alberto, Tomasi, Elisabetta, Raso, Nadia, Olimpi, Cristiana, Berti, Francesca, Matarazzo, Nicoletta, Galletti, Laura, Puppa, Marinella, Frasca, Alessandro, Barbieri, Chiara, Cinughi, Maria, Bandini, Iorio, Lezzi, Fabrizia, Verdelli, Renzo, Paradisi, Rita, Bindi, Cinzia Monica Sansone, Maria, Rosati, Federica, Zacchini, Simonetta, Baretti, Rossella, Cecconi, Chiara, Staderini, Poalo, Filidei, Elisabetta, Alfaroli, Franco, Barghini, Marina, Cadoni, Anna, Tosti, Giovannini, G, Giovanni, Piattellini, Alessandra, Buscosi, Anna, Pasquale, Carla, Ciani, Maria Claudia Paoloni, Franco, Santocchia, Maria Laura Proietti, Daniel, Fiacchini, Dzenana, Hazurovic, Maria Sole Giamprini, Katia, Gatti, Jacqueline Van Will, Alfredo, Vaccaro, Maria Margherita Sbarbati, Alessandra, Amelio, Daniela, Cimini, Vania, Moroni, Daniela, Francoletti, Federica, Scaccia, Elisabetta, Branchesi, Selena, Saracino, Catia, Mezzanotte, Susanna, Cimica, Vita, Vitale, Franca, Laici, Irene, Petrelli, Barbara, Airini, Gabriella, Passarini, Lucia, Ruffini, Anna Maria Lambertucci, Annarita, Mogetta, Francesca, Cioccoloni, Giuseppe, Ciarrocchi, Marina, Pistolesi, Erika, Fratello, Francesca, Picciotti, Claudio, Angelini, Paola, Scognamiglio, Francesco, Vairo, Andreina, Ercole, Antonio Salvatore Maglietta, Fabrizio, Magrelli, Fabrizio, Perrelli, Carlo, Cerocchi, Paolo, Grillo, Cristina, Vazzoler, Maria Rosaria Loffredo, Alessio, Pendenza, Maria Rosaria Nappi, Paola, Bueti, Luigi, Santucci, Franca, Mangiagli, Donatella, Varrenti, Silvia, Aquilani, Pietro, Dionette, Daniela, Corpolongo, Giuseppe Di Luzio, Manuela Di Giacomo, Enrico, Giansanti, Cristiana, Mancini, Claudio, Turchi, Carla, Granchelli, Graziella, Soldato, Felesina, D'Eugenio, Ida, Albanesi, Maria Antonietta Ferrara, Annarita, Citarella, Elena, Fossi, Rosa, Alfieri, Milena, Scotto, Anna Luisa Caiazzo, Rosa, Prato, Maria, Chironna, Domenico, Martinelli, Francesca, Fortunato, Maria Giovanna Cappelli, Daniela, Loconsole, Anna, Morea, Giulia Del Matto, Raffaele, Angelillis, Marcello, Antonazzo, Valerio, Aprile, Grazia Maria Avella, Roberta, Cambria, Giovanni, Caputi, Rosati, Cipriani, Carlo De Santis, Francesco, Desiante, Marisa, Ferraro, Vera, Laforgia, Antonino, Madaro, Maria Giuseppina Maluccio, Anna Maria Matera, Stefania, Menolascina, Giuseppina, Moffa, Maria, Nesta, Rita, Olivieri, Onofrio, Pagone, Pasquale, Pedote, Rosella, Squicciarini, Stefano, Termite, Viviana, Vitale, Francesco, Negrone, Manuela, Maldini, Giovanni, Laugello, Teresa, Russo, Anna Domenica Mignuoli, Giuseppe, Afflitto, Benedetto, Caroleo, Maria, Montesanti, Vincenzo De Giorgio, Antonio, Maradei, Rocco Cataldo Romeo, Francesca, Scrivano, Elisa, Lazzarino, Vittoria, Surace, Antonella, Giordano, Alessandro, Bisbano, Anita, Arcuri, Ida, Valentini, Rossana, Mangione, Valentina, Meli, Mario, Cuccia, Elena, Longhitano, Fiorenzo, Delogu, Donatella, Fracasso, Maria Vittoria Marceddu, Antonina, Puggioni, Maria Valentina Eugenua Marras, Rita, Serpi, Simonetta, Santus, Valentina, Marras, Stroffolini, Tommaso, Morisco, Filomena, Ferrigno, Luigina, Pontillo, Giuseppina, Iantosca, Giuseppina, Cossiga, Valentina, Crateri, Simonetta, and Tosti, Maria Elena

Subjects
Adult, Male, medicine.medical_specialty, HBsAg, Hepatitis B virus, viruses, Population, hepatitis delta, medicine.disease_cause, Virology, Internal medicine, Epidemiology, medicine, Humans, hepatitis B vaccination, education, Hepatitis, education.field_of_study, Hepatitis B Surface Antigens, Hepatology, business.industry, Immunization Programs, Incidence (epidemiology), virus diseases, biochemical phenomena, metabolism, and nutrition, medicine.disease, Hepatitis B, Hepatitis D, Vaccination, Infectious Diseases, surveillance, epidemiology, Female, Hepatitis Delta Virus, business, Viral hepatitis
Abstract

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p

Published
2021

25. Risk stratification of HCC occurrence after HCV eradication: a complicate plot of risk factors related and unrelated to the previous viral disease

Author

Nicola Caporaso, Filomena Morisco, Valentina Cossiga, Maria Guarino, Cossiga, Valentina, Guarino, Maria, Morisco, Filomena, and Caporaso, Nicola

Subjects
Oncology, medicine.medical_specialty, Cirrhosis, business.industry, Hepatitis C virus, Cancer, medicine.disease_cause, medicine.disease, digestive system diseases, 03 medical and health sciences, Editorial, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Hepatocellular carcinoma, Risk stratification, medicine, 030211 gastroenterology & hepatology, Viral disease, Risk factor, business
Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most frequent cause of cancer-related death worldwide. Hepatitis C virus (HCV) infection is one of leading cause of cirrhosis, that is the strongest risk factor for the development of HCC in Western countries (1,2).

Published
2020
Full Text
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26. Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology

Author

Roberto Miraglia, Matteo Garcovich, Giulia Tosetti, Nicola Caporaso, Agostino Colli, Antonio Rampoldi, Ioannis Petridis, Stella De Nicola, Angelo Andriulli, Marcello Dallio, Giovanni Perricone, G. Gobbo, Filomena Morisco, Antonio Gasbarrini, Pietro Pozzoni, Giuseppe Malizia, Angelo Vanzulli, Gennaro D'Amico, Gianluca Svegliati Baroni, Angelo Luca, Francesco Salerno, Mario D'Amico, Manuela Merli, Luca S. Belli, Vincenzo La Mura, Luchino Chessa, A. Iacobellis, Giuseppe Tarantino, Marco Solcia, Cristiano Sgrazzutti, Lorenzo Ridola, Luigi Maruzzelli, Alessandro Federico, Aldo Airoldi, Luigi Addario, Riccardo Volpes, Massimo Primignani, D'Amico, G., Maruzzelli, L., Airoldi, A., Petridis, I., Tosetti, G., Rampoldi, A., D'Amico, M., Miraglia, R., De Nicola, S., La Mura, V., Solcia, M., Volpes, R., Perricone, G., Sgrazzutti, C., Vanzulli, A., Primignani, M., Luca, A., Malizia, G., Federico, A., Dallio, M., Andriulli, A., Iacobellis, A., Addario, L., Garcovich, M., Gasbarrini, A., Chessa, L., Salerno, F., Gobbo, G., Merli, M., Ridola, L., Baroni, G. S., Tarantino, G., Caporaso, N., Morisco, F., Pozzoni, P., Colli, A., Belli, L. S., D'Amico, Gennaro, Maruzzelli, Luigi, Airoldi, Aldo, Petridis, Ioanni, Tosetti, Giulia, Rampoldi, Antonio, D'Amico, Mario, Miraglia, Roberto, De Nicola, Stella, La Mura, Vincenzo, Solcia, Marco, Volpes, Riccardo, Perricone, Giovanni, Sgrazzutti, Cristiano, Vanzulli, Angelo, Primignani, Massimo, D'Angelo, Luca, Malizia, Giuseppe, Federico, Alessandro, Dallio, Marcello, Andriulli, Angelo, Iacobellis, Angelo, Addario, Luigi, Garcovich, Matteo, Gasbarrini, Antonio, Chessa, Luchino, Salerno, Francesco, Gobbo, Giulia, Merli, Manuela, Ridola, Lorenzo, Baroni, Gianluca Svegliati, Tarantino, Giuseppe, Caporaso, Nicola, Morisco, Filomena, Pozzoni, Pietro, Colli, Agostino, Belli, Luca Saverio, D'Amico, G, Maruzzelli, L, Airoldi, A, Petridis, I, Tosetti, G, Rampoldi, A, D'Amico, M, Miraglia, R, De Nicola, S, La Mura, V, Solcia, M, Volpes, R, Perricone, G, Sgrazzutti, C, Vanzulli, A, Primignani, M, Luca, A, Malizia, G, Federico, A, Dallio, M, Andriulli, A, Iacobellis, A, Addario, L, Garcovich, M, Gasbarrini, A, Chessa, L, Salerno, F, Gobbo, G, Merli, M, Ridola, L, Baroni, G, Tarantino, G, Caporaso, N, Morisco, F, Pozzoni, P, Colli, A, and Belli, L

Subjects
Adult, medicine.medical_specialty, Cirrhosis, Time Factors, medicine.medical_treatment, Validation Studies as Topic, Models, Biological, Severity of Illness Index, Cohort Studies, End Stage Liver Disease, Liver disease, Model for End-Stage Liver Disease, clinical prediction rule, Internal medicine, Post-hoc analysis, Medicine, Humans, Mortality, Aged, Hepatology, business.industry, cirrhosis, Middle Aged, medicine.disease, Prognosis, MELD, body regions, Italy, Cohort, Etiology, TIPS, Steatohepatitis, business, Transjugular intrahepatic portosystemic shunt, cirrhosi, Follow-Up Studies
Abstract

Background & Aims Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model. Methods In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses. Results In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD. Conclusions In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed. Lay summary While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.

Published
2021

27. Coffee Restores Expression of lncRNAs Involved in Steatosis and Fibrosis in a Mouse Model of NAFLD

Author

Salvatore Piro, Stefania Di Mauro, Alessandra Scamporrino, Maria Guido, Rosaria Maria Pipitone, Agnese Filippello, Valentina Cossiga, Roberta Malaguarnera, Francesco Purrello, Federico Salomone, Vincenzo Lembo, Filomena Morisco, Stefania Grimaudo, Di Mauro, Stefania, Salomone, Federico, Scamporrino, Alessandra, Filippello, Agnese, Morisco, Filomena, Guido, Maria, Lembo, Vincenzo, Cossiga, Valentina, Pipitone, Rosaria Maria, Grimaudo, Stefania, Malaguarnera, Roberta, Purrello, Francesco, Piro, Salvatore, and Pipitone, Rosaria

Subjects
lncRNA, Liver Cirrhosis, Male, medicine.medical_specialty, Gm16551, H19, NAFLD, coffee, Animals, Coffee, Disease Models, Animal, Fatty Liver, Gene Expression, Liver, Mice, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease, RNA, Long Noncoding, Coenzyme A, Circadian clock, Biology, Inbred C57BL, Article, chemistry.chemical_compound, Downregulation and upregulation, Fibrosis, Settore BIO/13 - Biologia Applicata, Internal medicine, medicine, TX341-641, Messenger RNA, Nutrition and Dietetics, Nutrition. Foods and food supply, Animal, Fatty liver, nutritional and metabolic diseases, medicine.disease, Endocrinology, chemistry, Lipogenesis, Disease Models, RNA, Long Noncoding, Steatosis, Food Science
Abstract

Background and aim: Coffee intake exerts protective effects against non-alcoholic fatty liver disease (NAFLD), although without fully cleared mechanisms. In this study we aimed to assess whether coffee consumption may influence the expression of long non-coding RNAs (lncRNAs) in the liver. Methods: C57BL/6J mice were fed a 12-week standard diet (SD), high-fat diet (HFD) or HFD plus decaffeinated coffee solution (HFD + coffee). Expression of specific lncRNAs involved in NAFLD was analyzed by real-time PCR. For the most differentially expressed lncRNAs, the analysis was also extended to their mRNA targets. Results: Decaffeinated coffee intake reduced body weight gain, prevented NAFLD, lowered hyperglycemia and hypercholesterolemia. NAFLD was associated with lower hepatic expression of Gm16551, a lncRNA inhibiting de novo lipogenesis, and higher expression of H19, a lncRNA promoting fibrogenesis. Coffee intake restored Gm16551 to levels observed in lean mice and downregulated gene expression of its targets acetyl coenzyme A carboxylase 1 and stearoyl coenzyme A desaturase 1. Furthermore, coffee consumption markedly decreased hepatic expression of H19 and of its target gene collagen alpha-1(I) chain; consistently, in mice fed HFD + coffee liver expression of αSMA protein returned to levels of mice fed SD. Expression of lncRNA involved in circadian clock such as fatty liver-related lncRNA 1 (FLRL1) and fatty liver-related lncRNA 2 (FLRL2) were upregulated by HFD and were also modulated by coffee intake. Conclusion. Hepatoprotective effects of coffee may be depending on the modulation of lncRNAs involved in key pathways of NAFLD onset and progression.

Published
2021

28. PNPLA3, TM6SF2, and MBOAT7 Influence on Nutraceutical Therapy Response for Non-alcoholic Fatty Liver Disease: A Randomized Controlled Trial

Author

Marcello Dallio, Carmelina Loguercio, Filomena Morisco, Alessandro Federico, Concetta Tuccillo, Mario Masarone, Marcello Persico, Mario Romeo, Dallio, M., Masarone, M., Romeo, M., Tuccillo, C., Morisco, F., Persico, M., Loguercio, C., Federico, A., Dallio, Marcello, Masarone, Mario, Romeo, Mario, Tuccillo, Concetta, Morisco, Filomena, Persico, Marcello, Loguercio, Carmelina, and Federico, Alessandro

Subjects
Medicine (General), medicine.medical_specialty, medicine.medical_treatment, Context (language use), nutraceutics, Gastroenterology, law.invention, R5-920, Insulin resistance, Randomized controlled trial, genome wide association studie, law, Oral administration, Internal medicine, insulin resistance, medicine, TBARS, Vitamin D and neurology, genetics, Original Research, systemic inflammation, business.industry, Vitamin E, Fatty liver, nutritional and metabolic diseases, nutraceutic, General Medicine, genome wide association studies, medicine.disease, Medicine, genetic, business
Abstract

Introduction: PNPLA3, TM6SF2, and MBOAT7 genes play a crucial role in non-alcoholic fatty liver disease (NAFLD) development and worsening. However, few data are available on their treatment response influence. The aim of this trial is to explore the effect derived from silybin-phospholipids complex (303 mg of silybin-phospholipids complex, 10 μg of vitamin D, and 15 mg of vitamin E twice a day for 6 months) oral administration in NAFLD patients carrying PNPLA3-rs738409, TM6SF2-rs58542926, or MBOAT7-rs641738 genetic variants.Materials and Methods: In all, 92 biopsy-proven NAFLD patients were grouped in 30 NAFLD wild type controls, 30 wild type treated patients, and 32 mutated treated ones. We assessed glycemia (FPG), insulinemia, HOMA-IR, aspartate and alanine aminotransferases (AST, ALT), C-reactive protein (CRP), thiobarbituric acid reactive substance (TBARS), stiffness, controlled attenuation parameter (CAP), dietary daily intake, and physical activity at baseline and end of treatment.Results: The wild-type treated group showed a significant improvement of FPG, insulinemia, HOMA-IR, ALT, CRP, and TBARS (p < 0.05), whereas no improvements were recorded in the other two study groups. NAFLD wild type treated patients showed higher possibilities of useful therapeutic outcome (p < 0.01), obtained from the prescribed therapeutic regimen, independently from age, sex, comorbidities, medications, CAP, and stiffness in comparison to the mutated group.Discussion: The assessed mutations are independently associated with no response to a silybin-based therapeutic regimen and could be considered as useful predictive markers in this context.Clinical Trial Registry Number:www.ClinicalTrials.gov, identifier: NCT04640324.

Published
2021

29. Risk Factors for Liver Decompensation and HCC in HCV-Cirrhotic Patients after DAAs: A Multicenter Prospective Study

Author

Maria Guarino, Mariarita Cannavò, Tommaso Stroffolini, Filomena Morisco, Alessandro Federico, Rosa G. Benigno, Marcello Dallio, Paola Begini, Flavia Lucia Lombardo, Massimo Marignani, Giuseppina Pontillo, Morisco, Filomena, Federico, Alessandro, Marignani, Massimo, Cannavò, Mariarita, Pontillo, Giuseppina, Guarino, Maria, Dallio, Marcello, Begini, Paola, Benigno, Rosa G, Lombardo, Flavia L, Stroffolini, Tommaso, Morisco, F., Federico, A., Marignani, M., Cannavo, M., Pontillo, G., Guarino, M., Dallio, M., Begini, P., Benigno, R. G., Lombardo, F. L., and Stroffolini, T.

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Cirrhosis, Independent predictor, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Liver stiffness, Internal medicine, Medicine, Liver decompensation, HCC, Prospective cohort study, RC254-282, DAA, liver decompensation, business.industry, Proportional hazards model, cirrhosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, virus diseases, DAAs, medicine.disease, digestive system diseases, liver stiffness, 030104 developmental biology, Oncology, HCV, 030211 gastroenterology & hepatology, business, cirrhosi
Abstract

Background: Prospective studies on predictors of liver-related events in cirrhotic subjects achieving SVR after DAAs are lacking. Methods: We prospectively enrolled HCV cirrhotic patients in four Italian centers between November 2015 and October 2017. SVR and no-SVR cases were compared according to the presence or absence of liver-related events during a 24-month follow-up. Independent predictors of liver-related events were evaluated by Cox regression analysis. Results: A total of 706 subjects started DAAs therapy. SVR was confirmed in 687 (97.3%). A total of 61 subjects (8.9%) in the SVR group and 5 (26.3%) in the no-SVR group had liver-related events (p &lt, 0.03). The incidence rate x 100 p/y was 1.6 for HCC, 1.7 for any liver decompensation, and 0.5 for hepatic death. Baseline liver stiffness (LSM) ≥ 20 kPa (HR 4.0, 95% CI 1.1–14.1) and genotype different from 1 (HR 7.5, 95% CI 2.1–27.3) were both independent predictors of liver decompensation. Baseline LSM &gt, 20 KPa (HR 7.2, 95% CI 1.9–26.7) was the sole independent predictor of HCC. A decrease in liver stiffness (Delta LSM) by at least 20% at the end of follow-up was not associated with a decreased risk of liver-related events. Conclusion: Baseline LSM ≥ 20 kPa identifies HCV cirrhotic subjects at higher risk of liver-related events after SVR.

Published
2021

30. Eradication of HCV in Renal Transplant Recipients and Its Effects on Quality of Life

Author

Pasquale Buonanno, L. Donnarumma, Silvia Camera, Lucia Ferreri, Massimo Sabbatini, Filomena Morisco, Ivana Capuano, Nicola Caporaso, Sabbatini, Massimo, Capuano, Ivana, Camera, Silvia, Ferreri, Lucia, Buonanno, Pasquale, Donnarumma, Laura, Caporaso, Nicola, and Morisco, Filomena

Subjects
Adult, Male, medicine.medical_specialty, Article Subject, Sofosbuvir, Immunology and Microbiology (all), lcsh:Medicine, Renal function, Hepacivirus, 030230 surgery, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Liver stiffness, Internal medicine, Ribavirin, Hcv hepatitis, medicine, Humans, Aged, Antiviral Agent, Hepaciviru, Biochemistry, Genetics and Molecular Biology (all), Proteinuria, General Immunology and Microbiology, business.industry, lcsh:R, General Medicine, Hepatitis C, Chronic, Middle Aged, Hepatitis C, Kidney Transplantation, Regimen, Treatment Outcome, Italy, chemistry, Renal transplant, Quality of Life, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, medicine.symptom, business, Human, medicine.drug
Abstract

Background. The use of direct antiviral agents (DAA) has radically modified the course of HCV hepatitis in renal patients. Aim of this study was to assess the effects of HCV eradication on quality of life (QOL) in renal transplant recipients (RTR), measured by CLDQ and SF-36. Methods. Sixteen RTR with well preserved GFR (mean: 60.3±19.3 ml/min) and chronic HCV infection with moderate liver stiffness (9.3±1.7 kPa) were given a sofosbuvir-based regimen for 12 weeks and had a 1 year follow-up. Results. At end of treatment (EOT) a complete viral clearance was observed in all the patients, with normalization of most laboratory data and a consistent reduction in liver stiffness. All these parameters remained stable after 1 year, as well as renal function and proteinuria. Questionnaire data showed consistent amelioration in different “emotional” domains at EOT, which persisted after 1 year and were associated with a globally improved QOL, although there was no change in most of the “physical” domains in both questionnaires. One patient under ribavirin developed an acute anemia and withdrew from the study, but no further adverse episode was observed throughout the study. Conclusions. Our data, while confirming the efficacy of oral DAA, show that HCV infection represents a heavy psychological burden in renal transplant recipients, greatly alleviated by viral eradication, which determines a significant improvement in QOL that represents an important outcome in management of all transplant recipients. This trial is registered with ISRCTN97560076.

Published
2018
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31. Dietary supplementation of vitamin D prevents the development of western diet‐induced metabolic, hepatic and cardiovascular abnormalities in rats

Author

Carmine Morisco, G. Mazzone, Maria D'Armiento, Carmine Del Giudice, Antonella Rossi, Giuseppe D'Argenio, Nicola Caporaso, Bruno Trimarco, Vincenzo Lembo, Filomena Morisco, Mazzone, Giovanna, Morisco, Carmine, Lembo, Vincenzo, D’Argenio, Giuseppe, D’Armiento, Maria, Rossi, Antonella, Giudice, Carmine Del, Trimarco, Bruno, Caporaso, Nicola, and Morisco, Filomena

Subjects
0301 basic medicine, Vitamin, insulin, medicine.medical_specialty, medicine.medical_treatment, vitamin D, 030204 cardiovascular system & hematology, Diabete, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, cardiovascular disease, Internal medicine, Diabetes mellitus, Western diet, HOMA, medicine, Vitamin D and neurology, Dietary supplementation, business.industry, Insulin, Gastroenterology, Fructose, Original Articles, medicine.disease, western diet, 030104 developmental biology, Endocrinology, Oncology, chemistry, business
Abstract

The western diet high in fat and fructose may cause metabolic disorders and cardiovascular diseases.To evaluate whether long-term daily vitamin DThree groups of rats were fed for 6 months with standard diet (SD), western diet (WD) or WD containing 23 IU/day/rat vitamin DSixty-one per cent of hepatocytes in WD rats had steatotic vacuoles compared with just 27% in rats on a WD plus vitamin DIn animal models of liver and cardiovascular metabolic damage, the supplementation of vitamin D

Published
2018
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32. Systematic review: interferon-free regimens for patients with HCV-related Child C cirrhosis

Author

A. Amoruso, Nicola Caporaso, Grazia Anna Niro, N. Andriulli, Michele Pier Luca Guarino, Monica Greco, M. Librandi, Antonio Massimo Ippolito, Maria Rosa Valvano, Filomena Morisco, Angelo Andriulli, A. Iacobellis, Guarino, Maria, Morisco, Filomena, Valvano, M. R, Ippolito, A. M, Librandi, M, Andriulli, N, Greco, M, Amoruso, A, Iacobellis, A, Niro, G, Caporaso, Nicola, and Andriulli, A.

Subjects
Liver Cirrhosis, Ledipasvir, Simeprevir, medicine.medical_specialty, Cirrhosis, Daclatasvir, Sofosbuvir, Hepatitis C virus, medicine.disease_cause, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Internal medicine, medicine, Humans, Protease Inhibitors, Pharmacology (medical), Hepatology, business.industry, Ribavirin, Gastroenterology, medicine.disease, Hepatitis C, Surgery, chemistry, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Interferons, business, medicine.drug
Abstract

SummaryBackground It is unclear whether the efficacy and long-term outcome of treating patients with hepatitis C virus (HCV)-positive cirrhosis with the new protease inhibitors will extend to those with Child C cirrhosis. Aim To assess the effectiveness of the interferon-free regimens in Child C cirrhotic patients with HCV infection. Methods A systematic Medline search was conducted to retrieve studies describing the treatment of Child C patients with direct-acting agents. Citations from identified studies were cross-referenced and abstracts from European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Disease (AASLD) meetings were checked. Extracted data were evaluated using a meta-analysis to calculate a weighted response rate. Results Seven full-text records and two conference abstracts were retained for analysis from the 649 records identified. Data from an Italian real-life trial were also interrogated. Information on treatment outcome was available for 228 of the 240 Child C patients evaluated in the 10 trials. Overall, the weighted mean sustained virological response (SVR12) was 74.9% (95% CI: 65.6–82.4%). Neither duration of treatment (24 or 12 weeks), nor addition of ribavirin influenced these rates. The weighted SVR12 was 65.4% (95% CI: 46.8–80.2) after sofosbuvir/simeprevir, 76.0% (95% CI: 54.4–89.3%) after sofosbuvir/daclatasvir and 83.0% (95% CI: 73.4–89.6) after sofosbuvir/ledipasvir. Some studies did not provide information on the rate of post-treatment relapse or functional improvement. However, in those studies that did provide such data, a relapse was documented in 12.1% of patients and an improvement of ≥2 points on the model for end-stage liver disease (MELD) score in 61.1% of patients. Conclusion The improvement in MELD scores strongly suggests HCV-positive patients with Child C cirrhosis should be treated with these agents.

Published
2017
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33. Liver resection is always a good choice for hepatocellular carcinoma (HCC) patients regardless of Barcelona Clinic Liver Cancer (BCLC) stage: the therapeutic hierarchy

Author

Nicola Caporaso, Filomena Morisco, Maria Guarino, Guarino, Maria, Caporaso, Nicola, and Morisco, Filomena

Subjects
Oncology, medicine.medical_specialty, Hierarchy, business.industry, MEDLINE, General Medicine, medicine.disease, BCLC Stage, Resection, Text mining, Internal medicine, Hepatocellular carcinoma, medicine, Liver cancer, business
Published
2020

34. Role of Liver Stiffness Measurement in Predicting HCC Occurrence in Direct-Acting Antivirals Setting: A Real-Life Experience

Author

Giovanna Valente, Alessio Trabucco, Barbara Guerrera, Ferdinando Carlo Sasso, Maria Guarino, Luigi Elio Adinolfi, Michele Imparato, Pia Clara Pafundi, Luca Rinaldi, Riccardo Nevola, Antonio Ascione, Natalina Iuliano, Alessandro Perrella, Filomena Morisco, Guido Piai, Luca Fontanella, Rinaldi, Luca, Guarino, Maria, Perrella, Alessandro, Pafundi, Pia Clara, Valente, Giovanna, Fontanella, Luca, Nevola, Riccardo, Guerrera, Barbara, Iuliano, Natalina, Imparato, Michele, Trabucco, Alessio, Sasso, Ferdinando Carlo, Morisco, Filomena, Ascione, Antonio, Piai, Guido, Adinolfi, Luigi Elio, Rinaldi, L., Guarino, M., Perrella, A., Pafundi, P. C., Valente, G., Fontanella, L., Nevola, R., Guerrera, B., Iuliano, N., Imparato, M., Trabucco, A., Sasso, F. C., Morisco, F., Ascione, A., Piai, G., and Adinolfi, L. E.

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Transient elastography, Physiology, Direct-acting antiviral, Antiviral Agents, Risk Assessment, Sensitivity and Specificity, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Elastic Modulus, Internal medicine, Humans, Medicine, HCC, business.industry, Liver Neoplasms, Liver stiffne, Reproducibility of Results, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Hepatology, medicine.disease, digestive system diseases, HCV cirrhosi, Liver, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, business, Risk assessment, Viral hepatitis
Abstract

The aim of this study was to evaluate the relationship between the liver stiffness measurement and the risk of developing hepatocellular carcinoma (HCC) in HCV cirrhotic patients undergoing new direct-acting antivirals.From April 2015 to April 2017, all consecutive HCV cirrhotic patients treated by direct-acting antivirals were enrolled. A liver stiffness measurement was computed at baseline, and an ultrasound evaluation was provided for all patients at baseline and every 6 months until 1 year after the stopping of the antiviral therapy. The diagnosis of HCC was performed according to international guidelines by imaging technique workup.Two hundred and fifty-eight HCV patients with a diagnosis of cirrhosis were identified. The median liver stiffness was 25.5 kPa. Thirty-five patients developed HCC. Patients were divided into three groups, based on their liver stiffness: 20 kPa (n = 72), between 20 and 30 kPa (n = 92) and 30 kPa (n = 94). Compared to the 20 kPa and 20-30 kPa groups, the 30 kPa group showed a statistically significant increased risk of HCC (p = 0.019; HR 0.329; 95% CI 0.131-0.830). A ROC curve analysis to assess the overall predictive performance of liver stiffness measurement on the HCC risk was performed. The results allow us to identify a cutoff value of liver stiffness measurement equal to 27.8 kPa, which guarantees the highest sensitivity and specificity (respectively, 72% and 65%).The data underline that the baseline liver stiffness measurement and ultrasound surveillance is a valuable tool for assessing the risk of HCC in cirrhotic patients undergoing the direct-acting antivirals treatment.

Published
2019

35. Real-life glecaprevir/pibrentasvir in a large cohort of patients with hepatitis C virus infection: The MISTRAL study

Author

Marcello Persico, Andrea Aglitti, Pietro Gatti, Antonio Patrizio Termite, Benedetto Caroleo, Carmine Coppola, Michele Milella, Paolo Tundo, Vincenzo Messina, Alessandro Federico, Filomena Morisco, Luca Fontanella, Fernando Sogari, Giovan Giuseppe Di Costanzo, Irene Terrenato, Giuseppina Brancaccio, Gaetano Serviddio, Lorenzo Surace, Paola Pierri, Raffaele Cozzolongo, Annamaria Longo, Mario Masarone, Valerio Rosato, Ivan Gentile, Nicola Coppola, Ernesto Claar, Persico, Marcello, Aglitti, Andrea, Milella, Michele, Coppola, Carmine, Messina, Vincenzo, Claar, Ernesto, Gentile, Ivan, Sogari, Fernando, Pierri, Paola, Surace, Lorenzo A, Morisco, Filomena, Tundo, Paolo, Brancaccio, Giuseppina, Serviddio, Gaetano, Gatti, Pietro, Termite, Antonio P, Di Costanzo, Giovan G, Caroleo, Benedetto, Cozzolongo, Raffaele, Coppola, Nicola, Longo, Annamaria, Fontanella, Luca, Federico, Alessandro, Rosato, Valerio, Terrenato, Irene, Masarone, Mario, Persico, M., Aglitti, A., Milella, M., Coppola, C., Messina, V., Claar, E., Gentile, I., Sogari, F., Pierri, P., Surace, L. A., Morisco, F., Tundo, P., Brancaccio, G., Serviddio, G., Gatti, P., Termite, A. P., Di Costanzo, G. G., Caroleo, B., Cozzolongo, R., Coppola, N., Longo, A., Fontanella, L., Federico, A., Rosato, V., Terrenato, I., and Masarone, M.

Subjects
METAVIR Fibrosis Score, Cyclopropanes, Liver Cirrhosis, Male, Longitudinal study, Aminoisobutyric Acids, Pyrrolidines, Sustained Virologic Response, efficacy, Hepacivirus, 0302 clinical medicine, substance abuse, Longitudinal Studies, Prospective Studies, Substance Abuse, Intravenous, Aged, 80 and over, Sulfonamides, Hepatitis C, Middle Aged, Pibrentasvir, Italy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, Adult, medicine.medical_specialty, Genotype, Proline, Lactams, Macrocyclic, Antiviral Agents, Direct-acting antiviral, HCV genotype, cirrhosis, 03 medical and health sciences, Young Adult, Leucine, Internal medicine, Quinoxalines, medicine, Humans, Adverse effect, Aged, Hepatitis, direct-acting antiviral, Hepatology, business.industry, Glecaprevir, Hepatitis C, Chronic, medicine.disease, Benzimidazoles, business, Kidney disease, cirrhosi
Abstract

BACKGROUND AND AIMS It is paramount to identify predictors of treatment failure with direct antiviral agents in 'field-practice' patients, including people who inject drugs (PWID). Data on the efficacy of glecaprevir/pibrentasvir (GLE/PIB) in a field-practice scenario are scant. The multicentre MISTRAL study enrolled 1177 patients, including PWID, to assess real-life efficacy and safety of GLE/PIB and to identify the predictive factors for this treatment. METHODS This was a prospective, longitudinal study. The outcome variable was the rate of sustained virological response (SVR) at week 12. RESULTS A total of 123 patients (10%) were infected from hepatitis C virus (HCV) 3. METAVIR fibrosis score was F4 in 104 subjects (9%); 118 patients (10%) were PWID. Overall, 1163/1177 (99%) patients achieved SVR. The baseline clinical factors discriminating between treatment success and treatment failure were age at treatment (P = 0.031) and creatinine level (P = 0.034). SVR rates were not influenced by gender, substance abuse, previous treatment, treatment duration, fibrosis or chronic kidney disease stage. Compared with non-substance users, the 118 PWID exhibited a significantly different genotype pattern distribution (χ2

Published
2019

36. Incidence and risk factors of early HCC occurrence in HCV patients treated with direct acting antivirals: a prospective multicentre study

Author

Maria Guarino, Nicola Coppola, Luigi Elio Adinolfi, Guido Piai, Massimo De Luca, Antonio Izzi, Morena Fasano, Luca Rinaldi, Fortunato Ciardiello, Ferdinando Carlo Sasso, Riccardo Nevola, Filomena Morisco, Giovanna Valente, Alessandro Perrella, Caterina Monari, Pia Clara Pafundi, Lucia Miglioresi, Erika Martinelli, Barbara Guerrera, Massimiliano Berretta, Rinaldi, Luca, Perrella, Alessandro, Guarino, Maria, De Luca, Massimo, Piai, Guido, Coppola, Nicola, Pafundi, Pia Clara, Ciardiello, Fortunato, Fasano, Morena, Martinelli, Erika, Valente, Giovanna, Nevola, Riccardo, Monari, Caterina, Miglioresi, Lucia, Guerrera, Barbara, Berretta, Massimiliano, Sasso, Ferdinando Carlo, Morisco, Filomena, Izzi, Antonio, Adinolfi, Luigi Elio, Rinaldi, L., Perrella, A., Guarino, M., De Luca, M., Piai, G., Coppola, N., Pafundi, P. C., Ciardiello, F., Fasano, M., Martinelli, E., Valente, G., Nevola, R., Monari, C., Miglioresi, L., Guerrera, B., Berretta, M., Sasso, F. C., Morisco, F., Izzi, A., and Adinolfi, L. E.

Subjects
Liver Cirrhosis, Male, 0301 basic medicine, Cirrhosis, Sustained Virologic Response, Sofosbuvir, lcsh:Medicine, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Medicine, Cumulative incidence, Prospective Studies, HCC, Incidence, Incidence (epidemiology), HCV cirrhosis, Liver Neoplasms, General Medicine, Middle Aged, 030220 oncology & carcinogenesis, Female, Immune-surveillance, Off Treatment, medicine.drug, medicine.medical_specialty, Carcinoma, Hepatocellular, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, Direct acting antivirals, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Humans, Aged, business.industry, Research, Ribavirin, lcsh:R, Hepatitis C, Chronic, medicine.disease, digestive system diseases, Regimen, HCV cirrhosi, Logistic Models, 030104 developmental biology, chemistry, Multivariate Analysis, Direct acting antiviral, business
Abstract

Background An unexpected increased HCC recurrence and occurrence rate among HCV patients treated with direct acting antivirals combination has been reported. Aim of the study was the evaluation of early HCC occurrence rate and its risk factors in a HCV infected population, treated with direct-acting-antivirals. Methods According to the Italian ministerial guidelines for direct-acting-antivirals treatment, 1022 consecutive HCV patients treated with direct-acting-antivirals were enrolled. Patients either with active HCC at imaging or history of previous treated HCC, HBV or HIV co-infection, or liver transplant recipients were excluded. The SVR, defined as the persistent absence of detectable serum HCV-RNA 12 weeks after the end of treatment (SVR12), was assessed for all enrolled patients. Abdominal ultrasound was performed before starting antiviral therapy, and repeated every 6 months. HCC was diagnosed according to the international guidelines. Patients showing either nodular patterns suggestive of HCC or with uncertain dynamic vascular behaviour were excluded from a further follow-up. Results Nine hundred and eighty-five patients completed the 48 weeks follow-up after the end of treatment. A Sofosbuvir-based regimen was administered in the 74.9% of patients, among whom, the 71.6% underwent a simultaneous Ribavirin administration. A sustained virological response at 12 weeks off treatment was documented in 966 patients (98.2%). During the post treatment follow-up HCC was detected in 35 patients, with a cumulative incidence rate of the 3.55%. At multivariate analysis, four variables resulted independently associated with HCC development, both in a cirrhosis based and a class B Child based model, respectively: cirrhosis/class B Child, therapeutic schedule including Sofosbuvir without Ribavirin, liver stiffness values, male gender and presence of diabetes. A multivariate analysis performed on Child A cirrhotic patients, showed that Sofosbuvir based therapeutic treatment without Ribavirin had a HCC occurrence 5.7 higher than Ribavirin-based schedules with or without Sofosbuvir (p

Published
2019

37. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Author

Zobair M Younossi, Vlad Ratziu, Rohit Loomba, Mary Rinella, Quentin M Anstee, Zachary Goodman, Pierre Bedossa, Andreas Geier, Susanne Beckebaum, Philip N Newsome, David Sheridan, Muhammad Y Sheikh, James Trotter, Whitfield Knapple, Eric Lawitz, Manal F Abdelmalek, Kris V Kowdley, Aldo J Montano-Loza, Jerome Boursier, Philippe Mathurin, Elisabetta Bugianesi, Giuseppe Mazzella, Antonio Olveira, Helena Cortez-Pinto, Isabel Graupera, David Orr, Lise Lotte Gluud, Jean-Francois Dufour, David Shapiro, Jason Campagna, Luna Zaru, Leigh MacConell, Reshma Shringarpure, Stephen Harrison, Arun J Sanyal, Manal Abdelmalek, Gary Abrams, Humberto Aguilar, Aijaz Ahmed, Elmar Aigner, Guruprasad Aithal, Aftab Ala, William Alazawi, Agustin Albillos, Michael Allison, Sfa Al-Shamma, Raul Andrade, Pietro Andreone, Mario Angelico, Victor Ankoma-Sey, Quentin Anstee, Rodolphe Anty, Victor Araya, Juan Ignacio Arenas Ruiz, Perttu Arkkila, Marty Arora, Tarik Asselah, Jennifer Au, Oyekoya Ayonrinde, Robert James Bailey, Maya Balakrishnan, Kiran Bambha, Meena Bansal, Sidney Barritt, John Bate, Jorge Beato, Jaideep Behari, Pablo Bellot, Ziv Ben Ari, Michael Bennett, Marina Berenguer, Benedetta Terziroli Beretta-Piccoli, Thomas Berg, Maurizio Bonacini, Lucia Bonet, Brian Borg, Marc Bourliere, William Bowman, David Bradley, Marija Brankovic, Marius Braun, Jean-Pierre Bronowicki, Savino Bruno, Cindy Cai, Amy Calderon, José Luis Calleja Panero, Elizabeth Carey, Michal Carmiel, Jose Antonio Carrión, Matthew Cave, Cristina Chagas, Tawfik Chami, Alan Chang, Allan Coates, Jeremy Cobbold, Charlote Costentin, Kathleen Corey, Lynsey Corless, Javier Crespo, Oscar Cruz Pereira, Victor de Ledinghen, Andrew deLemos, Moises Diago, Mamie Dong, Jean-François Dufour, Predrag Dugalic, Winston Dunn, Magby Elkhashab, Michael Epstein, Maria Desamparados Escudero-Garcia, Ohad Etzion, Larry Evans, Robert Falcone, Conrado Fernandez, Jose Ferreira, Scott Fink, Kevin Finnegan, Roberto Firpi-Morell, Annarosa Floreani, Thierry Fontanges, Ryan Ford, Ewan Forrest, Andrew Fowell, Anna Ludovica Fracanzani, Sven Francque, Bradley Freilich, Juan Frias, Michael Fuchs, Javier Fuentes, Michael Galambos, Juan Gallegos, Anja Geerts, Jacob George, Maged Ghali, Reem Ghalib, Pierre Gholam, Pere Gines, Norman Gitlin, Tobias Goeser, John Goff, Stuart Gordon, Frederic Gordon, Odile Goria, Shaun Greer, Alla Grigorian, Henning Gronbaek, Maeva Guillaume, Naresh Gunaratnam, Dina Halegoua-De Marzio, Bilal Hameed, Stephanie Hametner, James Hamilton, Marek Hartleb, Tarek Hassanein, Dieter Häussinger, Paul Hellstern, Robert Herring, Eva Heurich, Christophe Hezode, Holger Hinrichsen, Peter Holland Fischer, Yves Horsmans, Jonathan Huang, Hyder Hussaini, Antoine Jakiche, Lennox Jeffers, Blake Jones, Rosa Jorge, Francisco Jorquera, Shoba Joshi, Alisan Kahraman, Kelly Kaita, Nicholas Karyotakis, Zeid Kayali, Stergios Kechagias, Thomas Kepczyk, Mandana Khalili, Hicham Khallafi, Johannes Kluwe, Anita Kohli, Kevin Korenblat, Kris Kowdley, Aleksander Krag, Richard Krause, Andreas Kremer, Karen Krok, Miodrag Krstic, Marcelo Kugelmas, Sonal Kumar, Scott Kuwada, Damien Labarriere, Michelle Lai, Wim Laleman, Pietro Lampertico, Alice Lee, Vincent Leroy, Steven Lidofsky, Tina Huey Lim, Joseph Lim, Donald Lipkis, Ester Little, Amadeo Lonardo, Michelle Long, Velimir Anthony Christopher Luketic, Yoav Lurie, Guilherme Macedo, Joana Magalhaes, Mihály Makara, Benedict Maliakkal, Michael Manns, Pinelopi Manousou, Parvez Mantry, Giulio Marchesini, Carla Marinho, Paul Marotta, Hanns-Ulrich Marschall, Linda Martinez, Marlyn Mayo, Mark McCullen, William McLaughlin, Uta Merle, Raphael Merriman, Apurva Modi, Esther Molina, Aldo Montano-Loza, Carlos Monteverde, Amilcar Morales Cardona, Sulleman Moreea, Christophe Moreno, Filomena Morisco, Abdullah Mubarak, Beat Muellhaupt, Sandeep Mukherjee, Tobias Müller, Aleksandar Nagorni, Jahnavi Naik, Guy Neff, Moises Nevah, Philip Newsome, Eric Nguyen-Khac, Mazen Noureddin, Jude Oben, Hans Orlent, James Orr, Grisell Ortiz-Lasanta, Violaine Ozenne, Prashant Pandya, Angelo Paredes, James Park, Joykumar Patel, Keyur Patel, Sonali Paul, Heather Patton, Markus Peck-Radosavljevic, Salvatore Petta, Stephen Pianko, Anna Piekarska, Neville Pimstone, Joseph Pisegna, Paul Pockros, Stanislas Pol, Michael Porayko, John Poulos, David Pound, Joe Pouzar, Jose Presa Ramos, Nikolaos Pyrsopoulos, Nila Rafiq, Kate Muller, Alnoor Ramji, Ravi Ravinuthala, Chakradhar Reddy, Gautham Reddy K G, K. Rajender Reddy K R, Frederic Regenstein, Robert Reindollar, Justin Reynolds, Andres Riera, Jose Rivera Acosta, Geert Robaeys, Stuart Roberts, Federico Rodriguez-Perez, Sandor Romero, Manuel Romero-Gomez, Raymond Rubin, Mariagrazia Rumi, Simon Rushbrook, Christian Rust, Michael Ryan, Rifaat Safadi, Adnan Said, Kimmo Salminen, Didier Samuel, John Santoro, Arun Sanyal, Souvik Sarkar, Cynthia Schaeffer, Jörn Schattenberg, Ingolf Schiefke, Eugene Schiff, Wolfgang Schmidt, Jeffrey Schneider, Jeoffrey Schouten, Michael Schultz, Giada Sebastiani, David Semela, Thomas Sepe, Aasim Sheikh, Muhammad Sheikh, Kenneth Sherman, Oren Shibolet, Mitchell Shiffman, Asma Siddique, Cyril Sieberhagen, Samuel Sigal, Katarzyna Sikorska, Krzysztof Simon, Marie Sinclair, Richard Skoien, Joel Solis, Siddharth Sood, Bob Souder, James Spivey, Per Stal, Laura Stinton, Simone Strasser, Petar Svorcan, Gyongzi Szabo, Andrew Talal, Edward Tam, Brent Tetri, Paul Thuluvath, Hillel Tobias, Krzysztof Tomasiewicz, Dawn Torres, Albert Tran, Michael Trauner, Christian Trautwein, Emanuel Tsochatzis, Esther Unitt, Victor Vargas, Istvan Varkonyi, Ella Veitsman, Umberto Vespasiani Gentilucci, David Victor, John Vierling, Catherine Vincent, Aron Vincze, Manfred von der Ohe, Natasha Von Roenn, Raj Vuppalanchi, Michael Waters, Kymberly Watt, Julia Wattacheril, Martin Weltman, Amanda Wieland, Gregory Wiener, Alonzo Williams A, Jeffrey Williams J, Jason Wilson, Maria Yataco, Eric Yoshida, Ziad Younes, Liyun Yuan, Adam Zivony, Donald Zogg, Heinz Zoller, Fabien Zoulim, Eli Zuckerman, Massimo Zuin, Younossi Z.M., Ratziu V., Loomba R., Rinella M., Anstee Q.M., Goodman Z., Bedossa P., Geier A., Beckebaum S., Newsome P.N., Sheridan D., Sheikh M.Y., Trotter J., Knapple W., Lawitz E., Abdelmalek M.F., Kowdley K.V., Montano-Loza A.J., Boursier J., Mathurin P., Bugianesi E., Mazzella G., Olveira A., Cortez-Pinto H., Graupera I., Orr D., Gluud L.L., Dufour J.-F., Shapiro D., Campagna J., Zaru L., MacConell L., Shringarpure R., Harrison S., Sanyal A.J., Abdelmalek M., Abrams G., Aguilar H., Ahmed A., Aigner E., Aithal G., Ala A., Alazawi W., Albillos A., Allison M., Al-Shamma S., Andrade R., Andreone P., Angelico M., Ankoma-Sey V., Anstee Q., Anty R., Araya V., Arenas Ruiz J.I., Arkkila P., Arora M., Asselah T., Au J., Ayonrinde O., Bailey R.J., Balakrishnan M., Bambha K., Bansal M., Barritt S., Bate J., Beato J., Behari J., Bellot P., Ben Ari Z., Bennett M., Berenguer M., Beretta-Piccoli B.T., Berg T., Bonacini M., Bonet L., Borg B., Bourliere M., Bowman W., Bradley D., Brankovic M., Braun M., Bronowicki J.-P., Bruno S., Cai C., Calleja Panero J.L., Carey E., Carmiel M., Carrion J.A., Cave M., Chagas C., Chami T., Chang A., Coates A., Cobbold J., Corey K., Corless L., Crespo J., Cruz Pereira O., de Ledinghen V., deLemos A., Diago M., Dugalic P., Dunn W., Elkhashab M., Epstein M., Escudero-Garcia M.D., Etzion O., Evans L., Falcone R., Fernandez C., Ferreira J., Fink S., Finnegan K., Firpi-Morell R., Floreani A., Fontanges T., Ford R., Forrest E., Fowell A., Fracanzani A.L., Francque S., Freilich B., Frias J., Fuchs M., Fuentes J., Galambos M., Gallegos J., Geerts A., George J., Ghali M., Ghalib R., Gholam P., Gines P., Gitlin N., Goeser T., Goff J., Gordon S., Gordon F., Goria O., Greer S., Grigorian A., Gronbaek H., Guillaume M., Gunaratnam N., Halegoua-De Marzio D., Hameed B., Hametner S., Hamilton J., Hartleb M., Hassanein T., Haussinger D., Hellstern P., Herring R., Heurich E., Hezode C., Hinrichsen H., Holland Fischer P., Horsmans Y., Huang J., Jakiche A., Jeffers L., Jones B., Jorge R., Jorquera F., Kahraman A., Kaita K., Karyotakis N., Kayali Z., Kechagias S., Kepczyk T., Khalili M., Khallafi H., Kluwe J., Kohli A., Korenblat K., Kowdley K., Krag A., Krause R., Kremer A., Krok K., Krstic M., Kugelmas M., Kumar S., Labarriere D., Lai M., Lampertico P., Lee A., Leroy V., Lidofsky S., Lim T.H., Lim J., Lipkis D., Little E., Lonardo A., Long M., Lurie Y., Macedo G., Makara M., Maliakkal B., Manns M., Manousou P., Mantry P., Marchesini G., Marinho C., Marotta P., Marschall H.-U., Mayo M., McCullen M., McLaughlin W., Merriman R., Modi A., Molina E., Montano-Loza A., Monteverde C., Moreea S., Moreno C., Morisco F., Mubarak A., Muellhaupt B., Mukherjee S., Muller T., Nagorni A., Naik J., Neff G., Nevah M., Newsome P., Nguyen-Khac E., Noureddin M., Oben J., Orlent H., Orr J., Ortiz-Lasanta G., Ozenne V., Pandya P., Paredes A., Park J., Patel J., Patel K., Uta M., Patton H., Peck-Radosavljevic M., Petta S., Pianko S., Piekarska A., Pimstone N., Pockros P., Pol S., Porayko M., Poulos J., Pound D., Pouzar J., Presa Ramos J., Pyrsopoulos N., Rafiq N., Muller K., Ramji A., Ravinuthala R., Reddy C., Reddy K G G., Reddy K R K.R., Regenstein F., Reindollar R., Riera A., Rivera Acosta J., Robaeys G., Roberts S., Rodriguez-Perez F., Romero-Gomez M., Rubin R., Rumi M., Rushbrook S., Rust C., Ryan M., Safadi R., Said A., Salminen K., Samuel D., Santoro J., Sanyal A., Sarkar S., Schaeffer C., Schattenberg J., Schiefke I., Schiff E., Schmidt W., Schneider J., Schouten J., Schultz M., Sebastiani G., Semela D., Sepe T., Sheikh A., Sheikh M., Sherman K., Shibolet O., Shiffman M., Siddique A., Sieberhagen C., Sigal S., Sikorska K., Simon K., Sinclair M., Skoien R., Solis J., Sood S., Souder B., Spivey J., Stal P., Stinton L., Strasser S., Svorcan P., Szabo G., Talal A., Tam E., Tetri B., Thuluvath P., Tobias H., Tomasiewicz K., Torres D., Trauner M., Trautwein C., Tsochatzis E., Unitt E., Vargas V., Varkonyi I., Veitsman E., Vespasiani Gentilucci U., Victor D., Vierling J., Vincent C., Vincze A., von der Ohe M., Von Roenn N., Vuppalanchi R., Waters M., Watt K., Weltman M., Wieland A., Wiener G., Williams A A., Williams J J., Wilson J., Yataco M., Yoshida E., Younes Z., Yuan L., Zivony A., Zogg D., Zoller H., Zoulim F., Zuckerman E., Zuin M., Repositório da Universidade de Lisboa, Younossi, Z. M., Ratziu, V., Loomba, R., Rinella, M., Anstee, Q. M., Goodman, Z., Bedossa, P., Geier, A., Beckebaum, S., Newsome, P. N., Sheridan, D., Sheikh, M. Y., Trotter, J., Knapple, W., Lawitz, E., Abdelmalek, M. F., Kowdley, K. V., Montano-Loza, A. J., Boursier, J., Mathurin, P., Bugianesi, E., Mazzella, G., Olveira, A., Cortez-Pinto, H., Graupera, I., Orr, D., Gluud, L. L., Dufour, J. -F., Shapiro, D., Campagna, J., Zaru, L., Macconell, L., Shringarpure, R., Harrison, S., Sanyal, A. J., Abdelmalek, M., Abrams, G., Aguilar, H., Ahmed, A., Aigner, E., Aithal, G., Ala, A., Alazawi, W., Albillos, A., Allison, M., Al-Shamma, S., Andrade, R., Andreone, P., Angelico, M., Ankoma-Sey, V., Anstee, Q., Anty, R., Araya, V., Arenas Ruiz, J. I., Arkkila, P., Arora, M., Asselah, T., Au, J., Ayonrinde, O., Bailey, R. J., Balakrishnan, M., Bambha, K., Bansal, M., Barritt, S., Bate, J., Beato, J., Behari, J., Bellot, P., Ben Ari, Z., Bennett, M., Berenguer, M., Beretta-Piccoli, B. T., Berg, T., Bonacini, M., Bonet, L., Borg, B., Bourliere, M., Bowman, W., Bradley, D., Brankovic, M., Braun, M., Bronowicki, J. -P., Bruno, S., Cai, C., Calleja Panero, J. L., Carey, E., Carmiel, M., Carrion, J. A., Cave, M., Chagas, C., Chami, T., Chang, A., Coates, A., Cobbold, J., Corey, K., Corless, L., Crespo, J., Cruz Pereira, O., de Ledinghen, V., Delemos, A., Diago, M., Dugalic, P., Dunn, W., Elkhashab, M., Epstein, M., Escudero-Garcia, M. D., Etzion, O., Evans, L., Falcone, R., Fernandez, C., Ferreira, J., Fink, S., Finnegan, K., Firpi-Morell, R., Floreani, A., Fontanges, T., Ford, R., Forrest, E., Fowell, A., Fracanzani, A. L., Francque, S., Freilich, B., Frias, J., Fuchs, M., Fuentes, J., Galambos, M., Gallegos, J., Geerts, A., George, J., Ghali, M., Ghalib, R., Gholam, P., Gines, P., Gitlin, N., Goeser, T., Goff, J., Gordon, S., Gordon, F., Goria, O., Greer, S., Grigorian, A., Gronbaek, H., Guillaume, M., Gunaratnam, N., Halegoua-De Marzio, D., Hameed, B., Hametner, S., Hamilton, J., Hartleb, M., Hassanein, T., Haussinger, D., Hellstern, P., Herring, R., Heurich, E., Hezode, C., Hinrichsen, H., Holland Fischer, P., Horsmans, Y., Huang, J., Jakiche, A., Jeffers, L., Jones, B., Jorge, R., Jorquera, F., Kahraman, A., Kaita, K., Karyotakis, N., Kayali, Z., Kechagias, S., Kepczyk, T., Khalili, M., Khallafi, H., Kluwe, J., Kohli, A., Korenblat, K., Kowdley, K., Krag, A., Krause, R., Kremer, A., Krok, K., Krstic, M., Kugelmas, M., Kumar, S., Labarriere, D., Lai, M., Lampertico, P., Lee, A., Leroy, V., Lidofsky, S., Lim, T. H., Lim, J., Lipkis, D., Little, E., Lonardo, A., Long, M., Lurie, Y., Macedo, G., Makara, M., Maliakkal, B., Manns, M., Manousou, P., Mantry, P., Marchesini, G., Marinho, C., Marotta, P., Marschall, H. -U., Mayo, M., Mccullen, M., Mclaughlin, W., Merriman, R., Modi, A., Molina, E., Montano-Loza, A., Monteverde, C., Moreea, S., Moreno, C., Morisco, F., Mubarak, A., Muellhaupt, B., Mukherjee, S., Muller, T., Nagorni, A., Naik, J., Neff, G., Nevah, M., Newsome, P., Nguyen-Khac, E., Noureddin, M., Oben, J., Orlent, H., Orr, J., Ortiz-Lasanta, G., Ozenne, V., Pandya, P., Paredes, A., Park, J., Patel, J., Patel, K., Uta, M., Patton, H., Peck-Radosavljevic, M., Petta, S., Pianko, S., Piekarska, A., Pimstone, N., Pockros, P., Pol, S., Porayko, M., Poulos, J., Pound, D., Pouzar, J., Presa Ramos, J., Pyrsopoulos, N., Rafiq, N., Muller, K., Ramji, A., Ravinuthala, R., Reddy, C., Reddy K G, G., Reddy K R, K. R., Regenstein, F., Reindollar, R., Riera, A., Rivera Acosta, J., Robaeys, G., Roberts, S., Rodriguez-Perez, F., Romero-Gomez, M., Rubin, R., Rumi, M., Rushbrook, S., Rust, C., Ryan, M., Safadi, R., Said, A., Salminen, K., Samuel, D., Santoro, J., Sanyal, A., Sarkar, S., Schaeffer, C., Schattenberg, J., Schiefke, I., Schiff, E., Schmidt, W., Schneider, J., Schouten, J., Schultz, M., Sebastiani, G., Semela, D., Sepe, T., Sheikh, A., Sheikh, M., Sherman, K., Shibolet, O., Shiffman, M., Siddique, A., Sieberhagen, C., Sigal, S., Sikorska, K., Simon, K., Sinclair, M., Skoien, R., Solis, J., Sood, S., Souder, B., Spivey, J., Stal, P., Stinton, L., Strasser, S., Svorcan, P., Szabo, G., Talal, A., Tam, E., Tetri, B., Thuluvath, P., Tobias, H., Tomasiewicz, K., Torres, D., Trauner, M., Trautwein, C., Tsochatzis, E., Unitt, E., Vargas, V., Varkonyi, I., Veitsman, E., Vespasiani Gentilucci, U., Victor, D., Vierling, J., Vincent, C., Vincze, A., von der Ohe, M., Von Roenn, N., Vuppalanchi, R., Waters, M., Watt, K., Weltman, M., Wieland, A., Wiener, G., Williams A, A., Williams J, J., Wilson, J., Yataco, M., Yoshida, E., Younes, Z., Yuan, L., Zivony, A., Zogg, D., Zoller, H., Zoulim, F., Zuckerman, E., Zuin, M., Younossi, Zobair M, Ratziu, Vlad, Loomba, Rohit, Rinella, Mary, Anstee, Quentin M, Goodman, Zachary, Bedossa, Pierre, Geier, Andrea, Beckebaum, Susanne, Newsome, Philip N, Sheridan, David, Sheikh, Muhammad Y, Trotter, Jame, Knapple, Whitfield, Lawitz, Eric, Abdelmalek, Manal F, Kowdley, Kris V, Montano-Loza, Aldo J, Boursier, Jerome, Mathurin, Philippe, Bugianesi, Elisabetta, Mazzella, Giuseppe, Olveira, Antonio, Cortez-Pinto, Helena, Graupera, Isabel, Orr, David, Gluud, Lise Lotte, Dufour, Jean-Francoi, Shapiro, David, Campagna, Jason, Zaru, Luna, MacConell, Leigh, Shringarpure, Reshma, Harrison, Stephen, Sanyal, Arun J, Abdelmalek, Manal, Abrams, Gary, Aguilar, Humberto, Ahmed, Aijaz, Aigner, Elmar, Aithal, Guruprasad, Ala, Aftab, Alazawi, William, Albillos, Agustin, Allison, Michael, Al-Shamma, Sfa, Andrade, Raul, Andreone, Pietro, Angelico, Mario, Ankoma-Sey, Victor, Anstee, Quentin, Anty, Rodolphe, Araya, Victor, Arenas Ruiz, Juan Ignacio, Arkkila, Perttu, Arora, Marty, Asselah, Tarik, Au, Jennifer, Ayonrinde, Oyekoya, Bailey, Robert Jame, Balakrishnan, Maya, Bambha, Kiran, Bansal, Meena, Barritt, Sidney, Bate, John, Beato, Jorge, Behari, Jaideep, Bellot, Pablo, Ben Ari, Ziv, Bennett, Michael, Berenguer, Marina, Beretta-Piccoli, Benedetta Terziroli, Berg, Thoma, Bonacini, Maurizio, Bonet, Lucia, Borg, Brian, Bourliere, Marc, Bowman, William, Bradley, David, Brankovic, Marija, Braun, Mariu, Bronowicki, Jean-Pierre, Bruno, Savino, Cai, Cindy, Calleja Panero, José Lui, Carey, Elizabeth, Carmiel, Michal, Carrión, Jose Antonio, Cave, Matthew, Chagas, Cristina, Chami, Tawfik, Chang, Alan, Coates, Allan, Cobbold, Jeremy, Corey, Kathleen, Corless, Lynsey, Crespo, Javier, Cruz Pereira, Oscar, de Ledinghen, Victor, deLemos, Andrew, Diago, Moise, Dufour, Jean-Françoi, Dugalic, Predrag, Dunn, Winston, Elkhashab, Magby, Epstein, Michael, Escudero-Garcia, Maria Desamparado, Etzion, Ohad, Evans, Larry, Falcone, Robert, Fernandez, Conrado, Ferreira, Jose, Fink, Scott, Finnegan, Kevin, Firpi-Morell, Roberto, Floreani, Annarosa, Fontanges, Thierry, Ford, Ryan, Forrest, Ewan, Fowell, Andrew, Fracanzani, Anna Ludovica, Francque, Sven, Freilich, Bradley, Frias, Juan, Fuchs, Michael, Fuentes, Javier, Galambos, Michael, Gallegos, Juan, Geerts, Anja, George, Jacob, Ghali, Maged, Ghalib, Reem, Gholam, Pierre, Gines, Pere, Gitlin, Norman, Goeser, Tobia, Goff, John, Gordon, Stuart, Gordon, Frederic, Goria, Odile, Greer, Shaun, Grigorian, Alla, Gronbaek, Henning, Guillaume, Maeva, Gunaratnam, Naresh, Halegoua-De Marzio, Dina, Hameed, Bilal, Hametner, Stephanie, Hamilton, Jame, Hartleb, Marek, Hassanein, Tarek, Häussinger, Dieter, Hellstern, Paul, Herring, Robert, Heurich, Eva, Hezode, Christophe, Hinrichsen, Holger, Holland Fischer, Peter, Horsmans, Yve, Huang, Jonathan, Jakiche, Antoine, Jeffers, Lennox, Jones, Blake, Jorge, Rosa, Jorquera, Francisco, Kahraman, Alisan, Kaita, Kelly, Karyotakis, Nichola, Kayali, Zeid, Kechagias, Stergio, Kepczyk, Thoma, Khalili, Mandana, Khallafi, Hicham, Kluwe, Johanne, Kohli, Anita, Korenblat, Kevin, Kowdley, Kri, Krag, Aleksander, Krause, Richard, Kremer, Andrea, Krok, Karen, Krstic, Miodrag, Kugelmas, Marcelo, Kumar, Sonal, Labarriere, Damien, Lai, Michelle, Lampertico, Pietro, Lee, Alice, Leroy, Vincent, Lidofsky, Steven, Lim, Tina Huey, Lim, Joseph, Lipkis, Donald, Little, Ester, Lonardo, Amadeo, Long, Michelle, Lurie, Yoav, Macedo, Guilherme, Makara, Mihály, Maliakkal, Benedict, Manns, Michael, Manousou, Pinelopi, Mantry, Parvez, Marchesini, Giulio, Marinho, Carla, Marotta, Paul, Marschall, Hanns-Ulrich, Mayo, Marlyn, McCullen, Mark, McLaughlin, William, Merriman, Raphael, Modi, Apurva, Molina, Esther, Montano-Loza, Aldo, Monteverde, Carlo, Moreea, Sulleman, Moreno, Christophe, Morisco, Filomena, Mubarak, Abdullah, Muellhaupt, Beat, Mukherjee, Sandeep, Müller, Tobia, Nagorni, Aleksandar, Naik, Jahnavi, Neff, Guy, Nevah, Moise, Newsome, Philip, Nguyen-Khac, Eric, Noureddin, Mazen, Oben, Jude, Orlent, Han, Orr, Jame, Ortiz-Lasanta, Grisell, Ozenne, Violaine, Pandya, Prashant, Paredes, Angelo, Park, Jame, Patel, Joykumar, Patel, Keyur, Uta, Merle, Patton, Heather, Peck-Radosavljevic, Marku, Petta, Salvatore, Pianko, Stephen, Piekarska, Anna, Pimstone, Neville, Pockros, Paul, Pol, Stanisla, Porayko, Michael, Poulos, John, Pound, David, Pouzar, Joe, Presa Ramos, Jose, Pyrsopoulos, Nikolao, Rafiq, Nila, Muller, Kate, Ramji, Alnoor, Ravinuthala, Ravi, Reddy, Chakradhar, Reddy K G, Gautham, Reddy K R, K. Rajender, Regenstein, Frederic, Reindollar, Robert, Riera, Andre, Rivera Acosta, Jose, Robaeys, Geert, Roberts, Stuart, Rodriguez-Perez, Federico, Romero-Gomez, Manuel, Rubin, Raymond, Rumi, Mariagrazia, Rushbrook, Simon, Rust, Christian, Ryan, Michael, Safadi, Rifaat, Said, Adnan, Salminen, Kimmo, Samuel, Didier, Santoro, John, Sanyal, Arun, Sarkar, Souvik, Schaeffer, Cynthia, Schattenberg, Jörn, Schiefke, Ingolf, Schiff, Eugene, Schmidt, Wolfgang, Schneider, Jeffrey, Schouten, Jeoffrey, Schultz, Michael, Sebastiani, Giada, Semela, David, Sepe, Thoma, Sheikh, Aasim, Sheikh, Muhammad, Sherman, Kenneth, Shibolet, Oren, Shiffman, Mitchell, Siddique, Asma, Sieberhagen, Cyril, Sigal, Samuel, Sikorska, Katarzyna, Simon, Krzysztof, Sinclair, Marie, Skoien, Richard, Solis, Joel, Sood, Siddharth, Souder, Bob, Spivey, Jame, Stal, Per, Stinton, Laura, Strasser, Simone, Svorcan, Petar, Szabo, Gyongzi, Talal, Andrew, Tam, Edward, Tetri, Brent, Thuluvath, Paul, Tobias, Hillel, Tomasiewicz, Krzysztof, Torres, Dawn, Trauner, Michael, Trautwein, Christian, Tsochatzis, Emanuel, Unitt, Esther, Vargas, Victor, Varkonyi, Istvan, Veitsman, Ella, Vespasiani Gentilucci, Umberto, Victor, David, Vierling, John, Vincent, Catherine, Vincze, Aron, von der Ohe, Manfred, Von Roenn, Natasha, Vuppalanchi, Raj, Waters, Michael, Watt, Kymberly, Weltman, Martin, Wieland, Amanda, Wiener, Gregory, Williams A, Alonzo, Williams J, Jeffrey, Wilson, Jason, Yataco, Maria, Yoshida, Eric, Younes, Ziad, Yuan, Liyun, Zivony, Adam, Zogg, Donald, Zoller, Heinz, Zoulim, Fabien, Zuckerman, Eli, Zuin, Massimo, and REGENERATE Study Investigators

Subjects
Male, Biopsy, Clinical Trial, Phase III, Administration, Oral, 030204 cardiovascular system & hematology, Chronic liver disease, Settore MED/04, Biomarkers/analysis, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Liver Function Tests, Non-alcoholic Fatty Liver Disease, Clinical endpoint, Medicine, 030212 general & internal medicine, 610 Medicine & health, Chenodeoxycholic Acid/administration & dosage, education.field_of_study, Liver Function Test, Research Support, Non-U.S. Gov't, Fatty liver, Obeticholic acid, NASH, OBETICHOLIC ACID, General Medicine, Middle Aged, Multicenter Study, Randomized Controlled Trial, Administration, Female, Biomarkers, Chenodeoxycholic Acid, Double-Blind Method, Humans, Human, Oral, medicine.medical_specialty, Population, Placebo, 03 medical and health sciences, Research Support, N.I.H., Extramural, Internal medicine, Journal Article, education, Intention-to-treat analysis, business.industry, Biomarker, Interim analysis, medicine.disease, Non-alcoholic Fatty Liver Disease/drug therapy, chemistry, Human medicine, business
Abstract

© 2019 Elsevier Ltd. All rights reserved., Background: Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods: In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings: Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation: Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.

Published
2019
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38. PNPLA3 rs738409 Polymorphism Predicts Development and Severity of Hepatic Steatosis but Not Metabolic Syndrome in Celiac Disease

Author

Luca Miele, Anna Alisi, Francesca Ferretti, Antonio Rispo, Raffaella Tortora, Valerio Nobili, Annalisa Crudele, Nicola Imperatore, Filomena Morisco, N. Gerbino, Nicola Caporaso, Tortora, Raffaella, Rispo, Antonio, Alisi, Anna, Imperatore, Nicola, Crudele, Annalisa, Ferretti, Francesca, Nobili, Valerio, Miele, Luca, Gerbino, Nicolò, Caporaso, Nicola, and Morisco, Filomena

Subjects
0301 basic medicine, Male, Gastroenterology, Severity of Illness Index, 0302 clinical medicine, Genotype, Membrane Protein, Allele, education.field_of_study, Nutrition and Dietetics, hepatic steatosis, Middle Aged, Liver, 030211 gastroenterology & hepatology, Female, lcsh:Nutrition. Foods and food supply, Human, Adult, medicine.medical_specialty, Waist, Adolescent, Logistic Model, Population, lcsh:TX341-641, Hepatic steatosi, Polymorphism, Single Nucleotide, Article, metabolic syndrome, 03 medical and health sciences, Diet, Gluten-Free, Young Adult, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, education, Genotyping, Alleles, PNPLA3, business.industry, Membrane Proteins, Odds ratio, Lipase, medicine.disease, Fatty Liver, 030104 developmental biology, Logistic Models, Steatosis, Metabolic syndrome, business, Body mass index, celiac disease, Food Science
Abstract

Metabolic syndrome (MS) and hepatic steatosis (HS) have been described in patients with celiac disease (CD) after starting a gluten-free diet (GFD), but data on predictive factors for these conditions are scarce. Recently, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 has been identified as a key factor for HS development in the general population. The aim of the study was to evaluate the role of PNPLA3 rs738409 in the development of MS and HS in CD patients after starting GFD. Between June 2014 and September 2016, we consecutively enrolled CD patients with HS, while those without steatosis served as a control group. All patients underwent anthropometric and serologic investigations, ultrasonography (US) to assess the degree and severity of HS, and genotyping of the PNPLA3 rs738409 polymorphism. Finally, 370 subjects were enrolled (136 with and 234 without HS). At genotyping assays, the CC genotype was found in 194 subjects (52.4%), the CG genotype in 138 subjects (37.3%), and the GG genotype in 38 subjects (10.2%). At binary logistic regression, only CG and GG alleles were predictive for the development of HS (odds ratio (OR) 1.97, p &lt, 0.01 for CG and OR 6.9, 0.001 for GG). Body mass index (BMI) (OR 3.8, 0.001) and waist circumference (OR 2.8, p = 0.03) at CD diagnosis were the only independent factors for the development of MS. Intergroup comparisons showed that the severe grade of HS was more frequently observed in GG than in CC carriers (74% vs. 11.3%, p &lt, 0.001, OR 21.8). PNPLA3 CG and GG carriers with CD have a higher susceptibility to hepatic steatosis, but not to metabolic syndrome. Moreover, patients with GG alleles display more severe forms of HS based on ultrasound.

Published
2018

39. Corrigendum to 'Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV' [J Hepatol 68 (2018) 33-41]

Author

Alessia Ciancio, Aimilia Karampatou, Tommaso Trenti, Veronica Bernabucci, Isabella Neri, Maria Guarino, Stefano Rosato, Laura Bristot, Filomena Morisco, Shivaji Manthena, Laura Turco, Simonetta Tagliavini, Gloria Taliani, Rosina Maria Critelli, Stefano Vella, Federica D'Ambrosio, Antonio La Marca, Savino Bruno, Andrea S. Goldstein, X. Han, Yanjun Bao, Giulia Troshina, Erica Villa, Yuri Sanchez Gonzalez, Enrica Baraldi, Loreta A. Kondili, Karampatou, Aimilia, Han, Xue, Kondili, Loreta A., Taliani, Gloria, Ciancio, Alessia, Morisco, Filomena, Critelli, Rosina Maria, Baraldi, Enrica, Bernabucci, Veronica, Troshina, Giulia, Guarino, Maria, Tagliavini, Simonetta, D'Ambrosio, Federica, Bristot, Laura, Turco, Laura, Rosato, Stefano, Vella, Stefano, Trenti, Tommaso, Neri, Isabella, La Marca, Antonio, Manthena, Shivaji, Goldstein, Andrea S., Bruno, Savino, Bao, Yanjun, Gonzalez, Yuri Sanchez, and Villa, Erica

Subjects
Gynecology, Senescence, medicine.medical_specialty, Mother to child transmission, Tenofovir, Hepatology, business.industry, media_common.quotation_subject, Hbv reactivation, Fertility, Hepatitis B, medicine.disease, Miscarriage, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, 030212 general & internal medicine, business, 030217 neurology & neurosurgery, medicine.drug, media_common
Published
2018

40. Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

Author

Giada Carolo, Veronica Bernabucci, Luchino Chessa, Maria Luisa Russo, Giorgio Maria Saracco, Marzia Montalbano, Barbara Menzaghi, Giovanni Di Perri, Adriano Lazzarin, Silvia La Monica, Raffaele Bruno, Gian Ludovico Rapaccini, Mario U. Mondelli, Anna Maria Schimizzi, Caterina Pasquazzi, Maurizia Rossana Brunetto, Antonio Craxì, Filomena Morisco, Carmela Lo Guercio, Vania Giacomet, Alessia Giorgini, Mario Masarone, Francesca Paolo Russo, T. Zolfino, Vincenzo Sangiovanni, Alessia Ciancio, Antonella d'Arminio Monforte, Savino Bruno, E.M. Erne, Antonio Gasbarrini, Francesco Castelli, Sergio Novara, G. Nardone, Andrea De Luca, Claudio Maria Mastroianni, Gioacchino Angarano, Chiara Dentone, Renato Maserati, Anna Maria Piscaglia, Tiziana Quirino, Giuseppe Tarantino, M. Lichtner, Antonio Chirianni, Giuseppina Brancaccio, S. Paganin, Alfredo Alberti, Silvia Corradori, Edoardo G. Giannini, Carlo Torti, Chiara Boarini, Raffaele Cozzolongo, Marco Di Stefano, Alessandro Soria, Paolo Tundi, Giovanni Cassola, Debora Angrisani, Antonio Grieco, Cecilia Pravadelli, Giuliano Rizzardini, Roberto Gulminetti, Vincenzo Messina, Maria Rendina, Massimo Pirisi, Irene Cacciola, Roberto Ganga, Raffaella Lionetti, Paolo Calabrese, Laura Ponti, Filomena Simeone, Maurizio Russello, Monica Monti, Nicola Boffa, Pierluigi Tarquini, Franco Capra, Ivo Avancini, Domenico Sansonno, Stefano Fagiuoli, Michele Barone, Giacomo Vecchiet, Salvatore Rizzo, Carlo Federico Perno, Teresa Santantonio, Pierluigi Toniutto, Massimo Zuin, Nicola Caporaso, Alessandra Orlandini, Grazielle Marie Pigozzi, Martina Felder, Antonio Cristaudo, Roberto Cecere, Massimo Marignani, Vincenza Calvaruso, G. Abbati, Domenico Potenza, Maria Chiara Piras, Mario Rizzetto, Serena Cima, Marco delle Monache, Alessio Aghemo, D. Ieluzzi, Guglielmo Borgia, Giampaolo Corti, Paolo Poggio, Manuela Merli, Elena Danieli, Andrea Giacometti, Massimo Andreoni, Antonino Picciotto, Mario Angelico, Benedetta Canovari, Sara Piovesan, Anna Linda Zignego, Antonio Benedetti, Emanuele Durante, Erica Villa, Marcello Persico, Antonio Patrizio Termite, Barbara Coco, Maria Vinci, Lucio Boglione, Cristina Rossi, Paolo Angeli, Massimo Memoli, Maria Teresa Giordani, Massimo De Luca, Luisa Pasulo, Vincenzo Vullo, Mario Melazzini, Attilio Solinas, Pietro Gatti, Michele Guerra, Silvia Martini, Antonio Ascione, Massimo Puoti, Roberto Cauda, Giovanna Onnelli, Silvia Magnani, Salvatore Madonna, Giovanni Raimondo, Marco Tabone, Gloria Taliani, Dante Romagnoli, Aldo Marrone, Umberto Vespasiani Gentilucci, Luca Miele, Marcello Tavio, Andrea Antinori, Giampiero D'Offizi, Mirella Onofrio, Valentina Iodice, Lucio Cosco, Guido Piai, Luca Pani, Francesca Ceccherini Silberstein, Simona Montilla, Marco Lenzi, Luca Fontanella, Alessandro Federico, Carlo Ferrari, Giustino Parruti, Antonio Di Biagio, Gabriella Verucchi, Fabio Marsetti, Michele Milella, Maria Grazia Rumi, Antonio Izzi, Marco Marzioni, Francesca Donato, Vanni Borghi, Mariano Quartini, Massimo Colombo, Michele Imparato, Giovanni Battista Gaeta, P.L. Blanc, Alfredo Di Leo, Nicola Coppola, Alessandro Chiodera, Ivana Maida, Davide Campagnolo, Cinzia Antonini, Antonietta Romano, A. Gianstefani, Katia Falasca, Massimo Levrero, Gaetano Serviddio, Maria Paola Trotta, Olivia Morelli, Salvatore Petta, Elisabetta Teti, Maria Rita Parisi, Pietro Andreone, Ascione, Antonio, De Luca, Massimo, Melazzini, Mario, Montilla, Simona, Trotta, Maria Paola, Petta, Salvatore, Puoti, Massimo, Sangiovanni, Vincenzo, Messina, Vincenzo, Bruno, Savino, Izzi, Antonio, Villa, Erica, Aghemo, Alessio, Zignego, Anna Linda, Orlandini, Alessandra, Fontanella, Luca, Gasbarrini, Antonio, Marzioni, Marco, Giannini, Edoardo G., Craxì, Antonio, Abbati, Giuseppe, Alberti, Alfredo, Andreone, Pietro, Andreoni, Massimo, Angeli, Paolo, Angelico, Mario, Angarano, Gioacchino, Angrisani, Debora, Antinori, Andrea, Antonini, Cinzia, Avancini, Ivo, Barone, Michele, Bruno, Raffaele, Benedetti, Antonio, Bernabucci, Veronica, Blanc, Pier, Boarini, Chiara, Boffa, Nicola, Boglione, Lucio, Borghi, Vanni, Borgia, Guglielmo, Brancaccio, Giuseppina, Brunetto, Maurizia, Cacciola, Irene, Calabrese, Paolo, Calvaruso, Vincenza, Campagnolo, Davide, Canovari, Benedetta, Caporaso, Nicola, Capra, Franco, Carolo, Giada, Cassola, Giovanni, Castelli, Francesco, Cauda, Roberto, Silberstein, Francesca Ceccherini, Cecere, Roberto, Chessa, Luchino, Chiodera, Alessandro, Chirianni, Antonio, Ciancio, Alessia, Cima, Serena, Coco, Barbara, Colombo, Massimo, Coppola, Nicola, Corti, Giampaolo, Cosco, Lucio, Corradori, Silvia, Cozzolongo, Raffaele, Cristaudo, Antonio, Danieli, Elena, Monforte, Antonella D’Arminio, Monache, Marco delle, Del Poggio, Paolo, de Luca, Andrea, Dentone, Chiara, Di Biagio, Antonio, Di Leo, Alfredo, Di Perri, Giovanni, Di Stefano, Marco, D’Offizi, Giampiero, Donato, Francesca, Durante, Emanuele, Erne, Elke, Fagiuoli, Stefano, Falasca, Katia, Federico, Alessandro, Felder, Martina, Ferrari, Carlo, Gaeta, Giovanni Battista, Ganga, Roberto, Gatti, Pietro, Giacomet, Vania, Giacometti, Andrea, Gianstefani, Alice, Giordani, Maria, Giorgini, Alessia, Grieco, Antonio, Guerra, Michele, Gulminetti, Roberto, Ieluzzi, Donatella, Imparato, Michele, Iodice, Valentina, La Monica, Silvia, Lazzarin, Adriano, Lenzi, Marco, Levrero, Massimo, Lichtner, Myriam, Lionetti, Raffaella, Guercio, Carmela Lo, Madonna, Salvatore, Magnani, Silvia, Maida, Ivana, Marignani, Massimo, Marrone, Aldo, Marsetti, Fabio, Martini, Silvia, Masarone, Mario, Maserati, Renato, Mastroianni, Claudio Maria, Memoli, Massimo, Menzaghi, Barbara, Merli, Manuela, Miele, Luca, Milella, Michele, Mondelli, Mario, Montalbano, Marzia, Monti, Monica, Morelli, Olivia, Morisco, Filomena, Nardone, Gaetano, Novara, Sergio, Onnelli, Giovanna, Onofrio, Mirella, Paganin, Simona, Pani, Luca, Parisi, Maria Rita, Parruti, Giustino, Pasquazzi, Caterina, Pasulo, Luisa, Perno, Carlo Federico, Persico, Marcello, Piai, Guido, Picciotto, Antonino, Pigozzi, Grazielle Marie, Piovesan, Sara, Piras, Maria Chiara, Pirisi, Massimo, Piscaglia, Anna Maria, Ponti, Laura, Potenza, Domenico, Pravadelli, Cecilia, Quartini, Mariano, Quirino, Tiziana, Raimondo, Giovanni, Rapaccini, Gian Ludovico, Rendina, Maria, Rizzardini, Giuliano, Rizzetto, Mario, Rizzo, Salvatore, Romagnoli, Dante, Romano, Antonietta, Rossi, Cristina, Rumi, Maria Grazia, Russello, Maurizio, Russo, Francesca Paolo, Russo, Maria Luisa, Sansonno, Domenico Ettore, Santantonio, Teresa Antonia, Saracco, Giorgio, Schimizzi, Anna Maria, Serviddio, Gaetano, Simeone, Filomena, Solinas, Attilio, Soria, Alessandro, Tabone, Marco, Taliani, Gloria, Tarantino, Giuseppe, Tarquini, Pierluigi, Tavio, Marcello, Termite, Antonio, Teti, Elisabetta, Toniutto, Pierluigi, Torti, Carlo, Tundi, Paolo, Vecchiet, Giacomo, Verucchi, Gabriella, Gentilucci, Umberto Vespasiani, Vinci, Maria, Vullo, Vincenzo, Zolfino, Teresa, Zuin, Massimo, Ascione, A, De Luca, M, Melazzini, M, Montilla, S, Trotta, M, Petta, S, Puoti, M, Sangiovanni, V, Messina, V, Bruno, S, Izzi, A, Villa, E, Aghemo, A, Zignego, A, Orlandini, A, Fontanella, L, Gasbarrini, A, Marzioni, M, Giannini, E, Craxi, A, Abbati, G, Alberti, A, Andreone, P, Andreoni, M, Angeli, P, Angelico, M, Angarano, G, Angrisani, D, Antinori, A, Antonini, C, Avancini, I, Barone, M, Bruno, R, Benedetti, A, Bernabucci, V, Blanc, P, Boarini, C, Boffa, N, Boglione, L, Borghi, V, Borgia, G, Brancaccio, G, Brunetto, M, Cacciola, I, Calabrese, P, Calvaruso, V, Campagnolo, D, Canovari, B, Caporaso, N, Capra, F, Carolo, G, Cassola, G, Castelli, F, Cauda, R, Silberstein, F, Cecere, R, Chessa, L, Chiodera, A, Chirianni, A, Ciancio, A, Cima, S, Coco, B, Colombo, M, Coppola, N, Corti, G, Cosco, L, Corradori, S, Cozzolongo, R, Cristaudo, A, Danieli, E, Monforte, A, Monache, M, Del Poggio, P, de Luca, A, Dentone, C, Di Biagio, A, Di Leo, A, Di Perri, G, Di Stefano, M, D'Offizi, G, Donato, F, Durante, E, Erne, E, Fagiuoli, S, Falasca, K, Federico, A, Felder, M, Ferrari, C, Gaeta, G, Ganga, R, Gatti, P, Giacomet, V, Giacometti, A, Gianstefani, A, Giordani, M, Giorgini, A, Grieco, A, Guerra, M, Gulminetti, R, Ieluzzi, D, Imparato, M, Iodice, V, La Monica, S, Lazzarin, A, Lenzi, M, Levrero, M, Lichtner, M, Lionetti, R, Guercio, C, Madonna, S, Magnani, S, Maida, I, Marignani, M, Marrone, A, Marsetti, F, Martini, S, Masarone, M, Maserati, R, Mastroianni, C, Memoli, M, Menzaghi, B, Merli, M, Miele, L, Milella, M, Mondelli, M, Montalbano, M, Monti, M, Morelli, O, Morisco, F, Nardone, G, Novara, S, Onnelli, G, Onofrio, M, Paganin, S, Pani, L, Parisi, M, Parruti, G, Pasquazzi, C, Pasulo, L, Perno, C, Persico, M, Piai, G, Picciotto, A, Pigozzi, G, Piovesan, S, Piras, M, Pirisi, M, Piscaglia, A, Ponti, L, Potenza, D, Pravadelli, C, Quartini, M, Quirino, T, Raimondo, G, Rapaccini, G, Rendina, M, Rizzardini, G, Rizzetto, M, Rizzo, S, Romagnoli, D, Romano, A, Rossi, C, Rumi, M, Russello, M, Russo, F, Russo, M, Sansonno, D, Santantonio, T, Saracco, G, Schimizzi, A, Serviddio, G, Simeone, F, Solinas, A, Soria, A, Tabone, M, Taliani, G, Tarantino, G, Tarquini, P, Tavio, M, Termite, A, Teti, E, Toniutto, P, Torti, C, Tundi, P, Vecchiet, G, Verucchi, G, Gentilucci, U, Vinci, M, Vullo, V, Zolfino, T, and Zuin, M

Subjects
Cyclopropanes, Liver Cirrhosis, Male, Cirrhosis, Dasabuvir, Elderly, Ombitasvir, Paritaprevir, Aged, 80 and over, Anilides, Antiviral Agents, Biomarkers, Carbamates, Female, Hepacivirus, Hepatitis C, Chronic, Humans, Macrocyclic Compounds, Ribavirin, Ritonavir, Sulfonamides, Treatment Outcome, Uracil, Drug Therapy, Combination, Genotype, Cirrhosis, Dasabuvir, Elderly, Ombitasvir, Paritaprevir, Microbiology (medical), Infectious Diseases, Aged, 80 and over, Hepatitis C, Chronic, Drug Therapy, Combination, Microbiology (medical), Infectious Diseases, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, 2-Naphthylamine, Medicine, 030212 general & internal medicine, Valine, General Medicine, 030211 gastroenterology & hepatology, Macrocyclic Compound, medicine.drug, Human, medicine.medical_specialty, Proline, Lactams, Macrocyclic, Settore MED/12 - GASTROENTEROLOGIA, Liver Cirrhosi, Sulfonamide, 03 medical and health sciences, Internal medicine, Decompensation, Hepatitis, Antiviral Agent, Cirrhosi, Hepaciviru, business.industry, Settore MED/09 - MEDICINA INTERNA, Anilide, Biomarker, medicine.disease, chemistry, Carbamate, business
Abstract

Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100mg) and twice-daily dasabuvir (250mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.

Published
2018

41. Characteristics and Changes over Time of Alcohol-Related Chronic Liver Diseases in Italy

Author

Filomena Morisco, Evangelista Sagnelli, Tommaso Stroffolini, Caterina Furlan, Sergio Babudieri, Caterina Sagnelli, Mariantonietta Pisaturo, Antonina Smedile, Piero Luigi Almasio, Maurizio Russello, Mario Pirisi, Stroffolini, Tommaso, Sagnelli, Evangelista, Sagnelli, Caterina, Morisco, Filomena, Babudieri, Sergio, Furlan, Caterina, Pirisi, Mario, Russello, Maurizio, Smedile, Antonina, Pisaturo, Mariantonietta, Almasio, Piero Luigi, Stroffolini, T., Sagnelli, E., Sagnelli, C., Morisco, F., Babudieri, S., Furlan, C., Pirisi, M., Russello, M., Smedile, A., Pisaturo, M., Almasio, P. L., and Almasio P.L.

Subjects
Liver Cirrhosis, Male, Cirrhosis, Chronic liver disease, Health Risk Behaviors, Health Risk Behavior, Liver disease, 0302 clinical medicine, Stage (cooking), Chronic, Liver Diseases, Gastroenterology, General Medicine, Hepatitis C, Health Survey, Middle Aged, Alcoholic, Alcoholism, Italy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Sex ratio, Adult, Aged, Alcohol Drinking, Chronic Disease, Health Surveys, Hepatitis C Antibodies, Hepatitis C, Chronic, Humans, Liver Diseases, Alcoholic, Research Article, Human, medicine.medical_specialty, Article Subject, Liver Cirrhosi, 03 medical and health sciences, Internal medicine, medicine, lcsh:RC799-869, Hepatology, business.industry, medicine.disease, Ageing, lcsh:Diseases of the digestive system. Gastroenterology, business, Hepatitis C Antibodie
Abstract

Introduction. To evaluate the characteristics of alcohol-related chronic liver disease (CLD) in Italy and their potential changes over time. Patients and Methods. Subjects with CLD were enrolled in two national surveys performed in 2001 and in 2014 in Italy. The two surveys prospectively recruited patients aged ≥ 18 years referring to more than 80 Italian liver units scattered all over the country using similar clinical approach, analytical methods, and threshold of risky alcohol intake definition (≥ 3 units/day in men and ≥ 2 units/day in women). Results. Out of 12,256 enrolled subjects, 2,717 (22.2%) reported a risky alcohol intake. Of them, anti-HCV positive was observed in 48.3% of subjects. The overall sex ratio (M/F) was 3.1, decreasing from 3.8 in 2001 to 1.3 in 2014. Women were significantly older than men (58.9 versus 53.1 years; p<0.01) and an increasing ageing over time was observed in both sexes. The proportion of subjects with liver cirrhosis increased over time in both sexes, and decompensated stage (Child B or C) was detected in 55.9% of cases in 2001 and 46.0% in 2014. Conclusions. Risky alcohol intake plays a role in more than one-fifth of CLD in Italy, with a shift over time towards an older age and a more severe liver disease stage. These data put alcohol back in the spotlight with an important role in CLD in the years to come in Italy.

Published
2018

42. Utility of Tumor Burden Score to Stratify Prognosis of Patients with Hepatocellular Cancer: Results of 4759 Cases from ITA.LI.CA Study Group

Author

Vitale, A, Lai, Q, Farinati, F, Bucci, L, Giannini, Eg, Napoli, L, Ciccarese, F, Rapaccini, Gl, Di Marco, M, Caturelli, E, Zoli, M, Borzio, F, Sacco, R, Cabibbo, G, Virdone, R, Marra, F, Felder, M, Morisco, F, Benvegnù, L, Gasbarrini, A, Svegliati-Baroni, G, Foschi, Fg, Missale, G, Masotto, A, Nardone, G, Colecchia, A, Bernardi, M, Trevisani, F, Pawlik, Tm, Italian Liver Cancer, (ITA. LI. CA) group., Vitale, Alessandro, Lai, Quirino, Farinati, Fabio, Bucci, Laura, Giannini, Edoardo G., Napoli, Lucia, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Bernardi, Mauro, Trevisani, Franco, Pawlik, Timothy M., and D'Alessandro, Vitale

Subjects
Oncology, Male, Hepatocellular carcinoma, Tumor burden, Disease, Severity of Illness Index, Milan Criteria, Outcomes, Prognosis, 0302 clinical medicine, Risk Factors, Outcome, education.field_of_study, Liver Neoplasms, Gastroenterology, Middle Aged, Survival Rate, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, alpha-Fetoproteins, medicine.medical_specialty, Carcinoma, Hepatocellular, Prognosi, Settore MED/12 - GASTROENTEROLOGIA, Population, Milan criteria, End Stage Liver Disease, 03 medical and health sciences, Internal medicine, medicine, Humans, Neoplasm Invasiveness, Risk factor, education, Survival analysis, Aged, Proportional Hazards Models, Retrospective Studies, Hepatocellular carcinoma, Milan Criteria, Outcomes, Prognosis, Tumor burden, Surgery, Gastroenterology, business.industry, Proportional hazards model, medicine.disease, Blood Vessels, Surgery, business
Abstract

Background: Dichotomous models like Milan Criteria represent the routinely used tools for predicting the outcome of patients with hepatocellular carcinoma (HCC). However, a paradigm shift from a dichotomous to continuous prognostic stratification should represent a good strategy for improving the prediction process. Recently, the tumor burden score (TBS) has been proposed for selecting patients with colorectal liver metastases. To date, TBS has not been validated in a large HCC population. The main objective of this study was to evaluate the prognostic power of TBS in an HCC population treated with different curative and palliative modalities. Methods: Prospectively collected data from consecutive HCC patients managed in 24 institutions participating in the ITA.LI.CA group between Jan 2002 and Mar 2015 were analyzed (n = 4759). A sub-analysis focused on 3909 patients with the radiological evidence of vascular invasion or metastatic disease was also performed. Results: TBS demonstrated the best discriminative ability when compared to MC and other tumor-specific scores. At multivariable Cox regression analysis, TBS was an independent risk factor of overall survival, with a 6% increased risk for patient death for each point increase in TBS. At survival analysis, when TBS ≥ 8 was connected with MELD ≥ 15 and alpha-fetoprotein ≥ 1000 ng/mL, patients presenting all these three risk factors presented the worst results (p value < 0.0001). Conclusions: Survival prediction of HCC patients was very well done using TBS model, even stratifying the population in relation to the presence of metastases and/or vascular invasion. TBS model was the best in terms of discriminatory ability and goodness of fit when compared with other continuous or binary variables. Its incorporation in a model composed by tumor- and liver function-related variables further increases its survival prediction.

Published
2018

43. Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study

Author

Vitale, A, Farinati, F, Noaro, G, Burra, P, Pawlik, Tm, Bucci, L, Giannini, Eg, Faggiano, C, Ciccarese, F, Rapaccini, Gl, Di Marco, M, Caturelli, E, Zoli, M, Borzio, F, Sacco, R, Cabibbo, G, Virdone, R, Marra, F, Felder, M, Morisco, F, Benvegnù, L, Gasbarrini, A, Svegliati-Baroni, G, Foschi, Fg, Olivani, A, Masotto, A, Nardone, G, Colecchia, A, Fornari, F, Marignani, M, Vicari, S, Bortolini, E, Cozzolongo, R, Grasso, A, Aliberti, C, Bernardi, M, Frigo, Ac, Borzio, M, Trevisani, F, Cillo, U, CA) group, Italian Liver Cancer (ITA. LI., Vitale, Alessandro, Farinati, Fabio, Noaro, Giulia, Burra, Patrizia, Pawlik, Timothy M., Bucci, Laura, Giannini, Edoardo G., Faggiano, Chiara, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Fornari, Fabio, Marignani, Massimo, Vicari, Susanna, Bortolini, Emanuela, Cozzolongo, Raffaele, Grasso, Alessandro, Aliberti, Camillo, Bernardi, Mauro, Frigo, Anna Chiara, Borzio, Mauro, Trevisani, Franco, and Cillo, Umberto

Subjects
Male, Oncology, Databases, Factual, Liver cancer, non surgical therapy, prognostic system, surgical therapy, survival, hepatocellular carcinoma, stage, treatment, Kaplan-Meier Estimate, Cohort Studies, Liver disease, 0302 clinical medicine, Middle Aged, Sorafenib, Prognosis, Italy, 030220 oncology & carcinogenesis, Catheter Ablation, Disease Progression, Female, 030211 gastroenterology & hepatology, medicine.drug, Cohort study, medicine.medical_specialty, Carcinoma, Hepatocellular, Settore MED/12 - GASTROENTEROLOGIA, Clinical Decision-Making, Risk Assessment, Disease-Free Survival, Statistics, Nonparametric, 03 medical and health sciences, Internal medicine, medicine, Hepatectomy, Humans, Infusions, Intra-Arterial, Neoplasm Invasiveness, Survival analysis, Aged, Neoplasm Staging, Retrospective Studies, Analysis of Variance, Hepatology, business.industry, Reproducibility of Results, Cancer, Retrospective cohort study, medicine.disease, Survival Analysis, business, Progressive disease
Abstract

Prognostic assessment of patients with hepatocellular carcinoma (HCC) at the time of diagnosis remains controversial and becomes even more complex at the time of restaging when new variables need to be considered. The aim of the current study was to evaluate the prognostic utility of restaging patients before proceeding with additional therapies for HCC. Two independent Italian prospective databases were used to identify 1,196 (training cohort) and 648 (validation cohort) consecutive patients with HCC treated over the same study period (2008-2015) who had complete restaging before decisions about additional therapies. The performance of the Italian Liver Cancer (ITA.LI.CA) prognostic score at restaging was compared with that of the Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, and Cancer of the Liver Italian Program systems. A multivariable Cox survival analysis was performed to identify baseline, restaging, or dynamic variables that were able to improve the predictive performance of the prognostic systems. At restaging, 35.3% of patients maintained stable disease; most patients were either down-staged by treatment (27.2%) or had disease progression (37.5%). The ITA.LI.CA scoring system at restaging demonstrated the best prognostic performance in both the training and validation cohorts (c-index 0.707 and 0.722, respectively) among all systems examined. On multivariable analysis, several variables improved the prognostic ability of the ITA.LI.CA score at restaging, including progressive disease after the first treatment, Model for End-Stage Liver Disease at restaging, and choice of nonsurgical treatment as additional therapy. A new ITA.LI.CA restaging model was created that demonstrated high discriminative power in both the training and validation cohorts (c-index 0.753 and 0.745, respectively). Conclusion: Although the ITA.LI.CA score demonstrated the best prognostic performance at restaging, other variables should be considered to improve the prognostic assessment of patients at the time of deciding additional therapies for HCC.

Published
2018

44. Patients with advanced hepatocellular carcinoma need a personalized management: A lesson from clinical practice

Author

Giannini E. G., Bucci L., Garuti F., Brunacci M., Lenzi B., Valente M., Caturelli E., Cabibbo G., Piscaglia F., Virdone R., Felder M., Ciccarese F., Foschi F. G., Sacco R., Svegliati Baroni G., Farinati F., Rapaccini G. L., Olivani A., Gasbarrini A., Di Marco M., Morisco F., Zoli M., Masotto A., Borzio F., Benvegnu L., Marra F., Colecchia A., Nardone G., Bernardi M., Trevisani F, Olmi S, on behalf of Italian Liver Cancer (ITA. LI. CA) group, Giannini, E. G., Bucci, L., Garuti, F., Brunacci, M., Lenzi, B., Valente, M., Caturelli, E., Cabibbo, G., Piscaglia, F., Virdone, R., Felder, M., Ciccarese, F., Foschi, F. G., Sacco, R., Svegliati Baroni, G., Farinati, F., Rapaccini, G. L., Olivani, A., Gasbarrini, A., Di Marco, M., Morisco, F., Zoli, M., Masotto, A., Borzio, F., Benvegnu, L., Marra, F., Colecchia, A., Nardone, G., Bernardi, M., Trevisani, F, Olmi, S, on behalf of Italian Liver Cancer (ITA. LI., CA) group, Giannini EG, Bucci L, Garuti F, Brunacci M, Lenzi B, Valente M, Caturelli E, Cabibbo G, Piscaglia F, Virdone R, Felder M, Ciccarese F, Foschi FG, Sacco R, Svegliati Baroni G, Farinati F, Rapaccini GL, Olivani A, Gasbarrini A, Di Marco M, Morisco F, Zoli M, Masotto A, Borzio F, Benvegnù L, Marra F, Colecchia A, Nardone G, Bernardi M, Trevisani F, Giannini, Edoardo G, Bucci, Laura, Garuti, Francesca, Brunacci, Matteo, Lenzi, Barbara, Valente, Matteo, Caturelli, Eugenio, Cabibbo, Giuseppe, Piscaglia, Fabio, Virdone, Roberto, Felder, Martina, Ciccarese, Francesca, Foschi, Francesco Giuseppe, Sacco, Rodolfo, Baroni, Gianluca Svegliati, Farinati, Fabio, Rapaccini, Gian Lodovico, Olivani, Andrea, Gasbarrini, Antonio, Di Marco, Maria, Morisco, Filomena, Zoli, Marco, Masotto, Alberto, Borzio, Franco, Benvegnù, Luisa, Marra, Fabio, Colecchia, Antonio, Nardone, Gerardo, Bernardi, Mauro, and Trevisani, Franco

Subjects
Sorafenib, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Databases, Factual, Settore MED/12 - GASTROENTEROLOGIA, advanced stage, Gastroenterology, survival, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, medicine, Carcinoma, Humans, Stage (cooking), Precision Medicine, Cancer staging, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, therapy, Hepatology, Performance status, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Prognosis, Survival Analysis, Liver cancer, sorafenib, Liver cancer, advanced stage, sorafenib, survival, therapy, Treatment Outcome, Liver, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, alpha-Fetoproteins, business, medicine.drug
Abstract

The Barcelona Clinic Liver Cancer advanced stage (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population, where sorafenib alone is the recommended treatment. In this study our aim was to assess treatment and overall survival (OS) of BCLC C patients sub-classified according to clinical features (Performance Status [PS], macro-vascular invasion [MVI], extra-hepatic spread [EHS] or MVI+EHS) determining their allocation to this stage. From the Italian Liver Cancer database, we analysed 835 consecutive BCLC C patients diagnosed between 2008 and 2014. Patients were sub-classified as: PS1 alone (n=385, 46.1%), PS2 alone (n=146, 17.5%), MVI (n=224, 26.8%), EHS (n=51, 6.1%) and MVI+EHS (n=29, 3.5%). MVI, EHS and MVI+EHS patients had larger and multifocal/massive HCCs and higher alpha-fetoprotein levels than PS1 and PS2 patients. Median OS significantly declined from PS1 (38.6 months) to PS2 (22.3 months), EHS (11.2 months), MVI (8.2 months) and MVI+EHS (3.1 months) (P

Published
2018

45. Geographical pattern of chronic liver diseases in Italy: Results from two pooled national surveys

Author

Antonina Smedile, Caterina Furlan, Piero Luigi Almasio, Tommaso Stroffolini, Evangelista Sagnelli, Filomena Morisco, Nicola Coppola, Caterina Sagnelli, Stroffolini, Tommaso, Sagnelli, Evangelista, Sagnelli, Caterina, Smedile, Antonina, Morisco, Filomena, Coppola, Nicola, Furlan, Caterina, Almasio, P.L., Almasio, Piero Luigi, Stroffolini, T., Sagnelli, E., Sagnelli, C., Smedile, A., Morisco, F., Coppola, N., Furlan, C., and Almasio, P. L.

Subjects
Adult, Liver Cirrhosis, Male, congenital, hereditary, and neonatal diseases and abnormalities, Alcohol, Chronic hepatitis, Geographical pattern, HBV, HCV, Liver cirrhosis, Liver cirrhosi, Hepatitis B, Chronic, Surveys and Questionnaires, Environmental health, Internal Medicine, Humans, Medicine, Liver Diseases, Alcoholic, Aged, Geography, business.industry, Liver Disease, Liver Diseases, Hepatitis C, Chronic, Middle Aged, respiratory tract diseases, Italy, Chronic Disease, Chronic hepatiti, Female, business, Human
Abstract

Background: The information on the geographical characteristics of chronic liver diseases (CLD) in Italy is out-dated. Aim: To provide up-dated information on the geographical pattern of patients with CLD born in Italy. Methods: Patients with CLD were enrolled in two national surveys performed in 2001 and 2014, which prospectively recruited subjects aged ≥18 years referring to Italian liver units located throughout the country that apply a similar clinical approach and analytical methods. Results: The total number of patients enrolled was 11,676. Alcohol-related CLD was more frequently observed in northern/central areas (25.0% vs. 20.7%, p < .001), while HBV-related (15.4% vs. 13.3%, p = .02) and HCV-related (71.2% vs. 67.1%, p < .001) CLD prevailed in southern areas/main islands (Sicily and Sardinia). These differences were stable over time. Liver cirrhosis without HCC was diagnosed more frequently in southern area/islands than in northern/central areas (23.7% vs. 18.8%, p < .01). Moreover, an increased proportion over time of patients with cirrhosis without HCC was observed both in northern/central areas (17.3% vs. 27.4%, p < .01) and in southern area/islands (22.6% vs. 27.9%, p < .01). Conclusions: These up-dated findings show different geographical patterns of CLD in Italy, reflecting different behavioural habits and socio-economic conditions across the country. They may be useful to apply more adequate preventive measures and to allocate economic resources.

Published
2018

46. Metabolic disorders across hepatocellular carcinoma in Italy

Author

Morisco, F., Guarino, M., Valvano, M. R., Auriemma, F., Farinati, F., Giannini, E. G., Ciccarese, F., Tovoli, F., Rapaccini, Gian Ludovico, Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cabibbo, G., Felder, M., Benvengu, L., Gasbarrini, Antonio, Svegliati Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Virdone, R., Marra, F., Caporaso, N., Trevisani, F., Sessa, A., Marafatto, F., Peserico, G., Pozzan, C., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Del Poggio, P., Olmi, S., De Matthaeis, Nicoletta, Balsamo, C., Vavassori, E., Roselli, P., Lauria, V., Pelecca, G., Mismas, V., Rossi, M., Attardo, S., Cavani, G., Mega, A., Rinninella, Emanuele, Ortolani, A., Bevilacqua, V., Chiara Dall'Aglio, A., Ercolani, G., Fiorini, Carlo Ettore, Casadei Gardini, A., Lanzi, Alessio, Mirici Cappa, F., Missale, G., Porro, E., Marchetti, F., Valerio, M., Affronti, A., Orlando, E., Rosa Barcellona, M., Aburas, S., Dragoni, G., Campani, C., Biselli, M., Bucci, L., Caraceni, P., Cucchetti, A., Domenicali, M., Garuti, F., Gramenzi, A., Magalotti, D., Serra, C., Granito, A., Negrini, G., Napoli, L., Piscaglia, F., Morisco, F., Guarino, M., Valvano, M. R., Auriemma, F., Farinati, F., Giannini, E. G., Ciccarese, F., Tovoli, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cabibbo, G., Felder, M., Benvengu, L., Gasbarrini, A., Svegliati Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Virdone, R., Marra, F., Caporaso, N., Trevisani, F., Sessa, A., Marafatto, F., Peserico, G., Pozzan, C., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Del Poggio, P., Olmi, S., de Matthaeis, N., Balsamo, C., Vavassori, E., Roselli, P., Lauria, V., Pelecca, G., Mismas, V., Rossi, M., Attardo, S., Cavani, G., Mega, A., Rinninella, E., Ortolani, A., Bevilacqua, V., Chiara Dall'Aglio, A., Ercolani, G., Fiorini, E., Casadei Gardini, A., Lanzi, A., Mirici Cappa, F., Missale, G., Porro, E., Marchetti, F., Valerio, M., Affronti, A., Orlando, E., Rosa Barcellona, M., Aburas, S., Dragoni, G., Campani, C., Biselli, M., Bucci, L., Caraceni, P., Cucchetti, A., Domenicali, M., Garuti, F., Gramenzi, A., Magalotti, D., Serra, C., Granito, A., Negrini, G., Napoli, L., Piscaglia, F., Morisco, Filomena, Guarino, Maria, Valvano, Maria R., Auriemma, Francesco, Farinati, Fabio, Giannini, Edoardo G., Ciccarese, Francesca, Tovoli, Francesco, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Felder, Martina, Benvengù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Foschi, Francesco G., Biasini, Elisabetta, Masotto, Alberto, Virdone, Roberto, Marra, Fabio, Caporaso, Nicola, Trevisani, Franco, Sessa, Anna, Marafatto, Filippo, Peserico, Giulia, Pozzan, Caterina, Brunacci, Matteo, Moscatelli, Alessandro, Pellegatta, Gaia, Savarino, Vincenzo, Del Poggio, Paolo, Olmi, Stefano, de Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Lauria, Valentina, Pelecca, Giorgio, Mismas, Valeria, Rossi, Margherita, Attardo, Simona, Cavani, Giulia, Mega, Andrea, Rinninella, Emanuele, Ortolani, Alessio, Bevilacqua, Vittoria, Chiara Dall'Aglio, Anna, Ercolani, Giorgio, Fiorini, Erica, Casadei Gardini, Andrea, Lanzi, Arianna, Mirici Cappa, Federica, Missale, Gabriele, Porro, Emanuela, Marchetti, Fabiana, Valerio, Matteo, Affronti, Andrea, Orlando, Emanuele, Rosa Barcellona, Maria, Aburas, Sami, Dragoni, Gabriele, Campani, Claudia, Biselli, Maurizio, Bucci, Laura, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Garuti, Francesca, Gramenzi, Annagiulia, Magalotti, Donatella, Serra, Carla, Granito, Alessandro, Negrini, Giulia, Napoli, Lucia, Piscaglia, Fabio, Valvano, Maria R, Giannini, Edoardo G, and Foschi, Francesco G

Subjects
Oncology, Male, obesity, Databases, Factual, Hepatocellular carcinoma, 0302 clinical medicine, Risk Factors, Prospective cohort study, diabetes, Metabolic disorder, Liver Neoplasms, Diabetes, hepatocellular carcinoma, Middle Aged, Metabolic syndrome, Portal vein thrombosis, Italy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, medicine.medical_specialty, Carcinoma, Hepatocellular, Settore MED/12 - GASTROENTEROLOGIA, Obesity, metabolic syndrome, 03 medical and health sciences, Databases, Metabolic Diseases, Internal medicine, medicine, Diabetes Mellitus, Humans, Factual, Aged, Neoplasm Staging, Retrospective Studies, Hepatology, business.industry, Carcinoma, Hepatocellular, medicine.disease, Survival Analysis, BCLC Stage, Multivariate Analysis, diabete, Liver function, business
Abstract

Background: Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. Methods: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features. Results: As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P=.021), larger tumours (P=.038), better liver function (higher percentage of Child-Pugh class A [P=.007] and MELD&nbsp

Published
2018

47. Silibinin Restores NAD+ Levels and Induces the SIRT1/AMPK Pathway in Non-Alcoholic Fatty Liver

Author

Vincenzo Lembo, Walter Currenti, Roberto Avola, Giovanni Li Volti, Filomena Morisco, Fabio Galvano, Ignazio Barbagallo, Diana Cinà, Federico Salomone, Justyna Godos, Nicolantonio D'Orazio, Salomone, Federico, Barbagallo, Ignazio, Godos, Justyna, Lembo, Vincenzo, Currenti, Walter, Cinà, Diana, Avola, Roberto, D’Orazio, Nicolantonio, Morisco, Filomena, Galvano, Fabio, and Li Volti, Giovanni

Subjects
0301 basic medicine, AMPK, medicine.medical_specialty, Silibinin, lcsh:TX341-641, Nicotinamide adenine dinucleotide, medicine.disease_cause, Diet, High-Fat, Gene Expression Regulation, Enzymologic, Article, 03 medical and health sciences, chemistry.chemical_compound, Mice, SIRT1, Sirtuin 1, Non-alcoholic Fatty Liver Disease, Internal medicine, NAD+, medicine, Animals, Humans, Obesity, Protein kinase A, lipogenesis, silibinin, Nutrition and Dietetics, Fatty liver, Adenylate Kinase, Lipogenesi, Hep G2 Cells, medicine.disease, NAD, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, Silybin, Lipogenesis, NAD+ kinase, lcsh:Nutrition. Foods and food supply, Oxidative stress, Silymarin, Food Science
Abstract

Nicotinamide adenine dinucleotide (NAD+) homeostasis is emerging as a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and is tightly linked to the SIRT1/5’-AMP-activated protein kinase (AMPK) pathway. Silibinin, the main component of silymarin, has been proposed as a nutraceutical for the treatment of NAFLD. In this study, we aimed to identify whether silibinin may influence the NAD+/SIRT1 axis. To this end, C57BL/6 mice were fed a high fat diet (HFD) for 16 weeks, and were treated with silibinin or vehicle during the last 8 weeks. HepG2 cells were treated with 0.25 mM palmitate for 24 h with silibinin 25 µM or vehicle. HFD and palmitate administration led to oxidative stress, poly-(ADP-ribose)-polymerase (PARP) activation, NAD+ consumption, and lower SIRT1 activity. In mice fed the HFD, and in HepG2 treated with palmitate, we consistently observed lower levels of phospho-AMPKThr172 and phospho-acetyl-CoA carboxylaseSer79 and higher levels of nuclear sterol regulatory element-binding protein 1 activity, indicating de novo lipogenesis. Treatment of mice and HepG2 with silibinin abolished oxidative stress, and inhibited PARP activation thus restoring the NAD+ pool. In agreement with preserved NAD+ levels, SIRT1 activity and AMPK phosphorylation returned to control levels in mice and HepG2. Our results further indicate silibinin as a promising molecule for the treatment of NAFLD.

Published
2017

48. Sustained virological response by direct antiviral agents in HCV leads to an early and significant improvement of liver fibrosis

Author

Antonio De Luna, Andrea Aglitti, Davide F Precone, Nicola Caporaso, Valerio Rosato, Mario Masarone, Silvia Camera, Marcello Dallio, Mariano Corrado, Marcello Persico, Alessandro Federico, Filomena Morisco, Ernesto Claar, Persico, Marcello, Rosato, Valerio, Aglitti, Andrea, Precone, Davide, Corrado, Mariano, De Luna, Antonio, Morisco, Filomena, Camera, Silvia, Federico, Alessandro, Dallio, Marcello, Claar, Ernesto, Caporaso, Nicola, and Masarone, Mario

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Genotype, Sustained Virologic Response, Liver fibrosis, Hepacivirus, Gastroenterology, Antiviral Agents, Severity of Illness Index, Virological response, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Liver stiffness, Recurrence, Internal medicine, Severity of illness, Hypertension, Portal, Medicine, Humans, Pharmacology (medical), Pharmacology, business.industry, Hepatitis C, Hepatitis C, Chronic, medicine.disease, Infectious Diseases, 030220 oncology & carcinogenesis, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, business, Biomarkers
Abstract

Background Direct antiviral agents (DAA) demonstrated high efficacy among HCV-infected patients in registered trials. Nevertheless, the impact of these therapies on liver stiffness measurement (LSM) and liver functionality in ‘real-life’ is not well-known. The aim of the present study was to evaluate the sustained virological response (SVR) impact on LSM and clinical parameters of DAA-therapy on a real-life population of HCV patients with F3/F4 fibrosis. Methods A total of 749 HCV genotype 1–4 patients with F3/F4 hepatitis undergoing antiviral therapy were consecutively enrolled in four centres of hepatology in Italy. Clinical, biochemical and imaging data were collected at the baseline (T0), at the end of treatment (EoT) and after 12 weeks (SVR12). Results Out of 749 patients, 69.7% were F4 and 30.3% were F3. SVR12 was reached in 97.5%. LSM significantly decreased from T0 to EoT ( PConclusions Virological response to DAA is associated with fibrosis regression and recovery of liver functionality and this can be detected as early as EoT. HCV eradication is associated with a rapid and significant clinical improvement that lasts over time and seems to be negatively influenced by diabetes and EV.

Published
2017

49. Circulating SCCA-IgM complex is a useful biomarker to predict the outcome of therapy in hepatocellular carcinoma patients

Author

Nicola Caporaso, Giovan Giuseppe Di Costanzo, Maria Guarino, Giorgio Fassina, Concetta Tuccillo, Andrea Gallotta, Raffaella Tortora, Laura Paneghetti, Francesco Auriemma, Filomena Morisco, Guarino, Maria, Di Costanzo, Giovan G., Gallotta, Andrea, Tortora, Raffaella, Paneghetti, Laura, Auriemma, Francesco, Tuccillo, Concetta, Fassina, Giorgio, Caporaso, Nicola, and Morisco, Filomena

Subjects
Oncology, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Hepatocellular carcinoma, squamous cell carcinoma-related antigen, Clinical Biochemistry, Treatment outcome, Squamous cell carcinoma Antigen, Sensitivity and Specificity, Body Mass Index, 03 medical and health sciences, antigen, 0302 clinical medicine, Antigen, Antigens, Neoplasm, Internal medicine, medicine, Biomarkers, Tumor, Humans, Serpins, Neoplasm Staging, biology, business.industry, Liver Neoplasms, serpin, General Medicine, medicine.disease, digestive system diseases, Treatment Outcome, Immunoglobulin M, ROC Curve, 030220 oncology & carcinogenesis, Area Under Curve, biology.protein, Biomarker (medicine), 030211 gastroenterology & hepatology, Neoplasm staging, Liver cancer, business
Abstract

Hepatocellular carcinoma (HCC) develops in about 3-4% of cirrhotic patients every year. The squamous cell carcinoma antigen (SCCA) has been found elevated in liver cancer specimens by immunohistochemistry, and detected in complex with IgM (SCCA-IgM) in the serum of patients with HCC. The aim of this study was to evaluate the ability of serological SCCA-IgM levels to predict the efficacy of HCC therapy.From April 2012 to April 2014, 131 patients with a new diagnosis of HCC were enrolled. The HCC diagnosis was made according to the EASL guidelines. The patients were staged and treated according to the BCLC Staging System: BCLC stages A and B were treated with locoregional therapy, and BCLC stage C was treated with Sorafenib. Response to therapy was evaluated according to the mRECIST criteria. Serum SCCA-IgM levels were determined by a commercially available ELISA kit at basal time (TAt baseline and one month into therapy, SCCA-IgM levels were significantly lower (p value.05) in patients who responded to therapy compared to those who did not respond (median SCCA-IgM level [25th + 75th percentile] at TOur study suggests that the SCCA-IgM determination could be helpful in predicting the response to therapy in patients with HCC.

Published
2017

50. Optimization of direct anti-viral agent treatment schedule: Focus on HCV genotype 3

Author

Maria Rosa Valvano, Silvia Camera, Angelo Andriulli, Marta Librandi, R. Granata, Vincenzo Messina, A. Iacobellis, Fabio Conti, Michele Milella, Filomena Morisco, Paolo Tundo, Pietro Gatti, Teresa Santantonio, A. Smedile, Nicola Caporaso, C. Masetti, Antonio Patrizio Termite, Antonio Massimo Ippolito, Morisco, Filomena, Granata, Rocco, Camera, Silvia, Ippolito, Antonio, Milella, Michele, Conti, Fabio, Masetti, Chiara, Smedile, Antonella, Tundo, Paolo, Santantonio, Teresa, Valvano, Maria Rosa, Termite, Antonio, Gatti, Pietro, Messina, Vincenzo, Iacobellis, Angelo, Librandi, Marta, Caporaso, Nicola, and Andriulli, Angelo

Subjects
Ledipasvir, medicine.medical_specialty, Cirrhosis, Sofosbuvir, Hepatitis C virus, medicine.disease_cause, Gastroenterology, meta-analysi, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Genotype, medicine, genotype 3, 030212 general & internal medicine, direct antiviral agent, business.industry, Ribavirin, virus diseases, Original Articles, medicine.disease, digestive system diseases, chemistry, Oncology, Treatment Schedule, Meta-analysis, HCV, 030211 gastroenterology & hepatology, business, medicine.drug, cirrhosi
Abstract

Direct antiviral agents (DAAs) have led to high sustained virological responses (SVR) in hepatitis C virus (HCV) patients. However, genotype 3 patients respond to treatment in a suboptimal way. This study aims to identify which of the several treatment schedules recommended for genotype 3 would constitute the best option.Twenty-four Italian centers were involved in this real-life study of HCV genotype 3 patients treated with DAAs. To expand the number of cases, we conducted a systematic review of the literature on the outcome of genotype 3 patients treated with DAAs.A total of 233 patients with HCV genotype 3 were enrolled. Cirrhotic patients accounted for 83.7%. Overall, the SVR12 rate was achieved by 205 patients (88.0%); the SVR rates were 78.8% after sofosbuvir/ribavirin, 92.5% after sofosbuvir/daclatasvir ± ribavirin, and 100% after sofosbuvir/ledipasvir (seven patients). No difference in rate of SVR was observed in cirrhotic and non-cirrhotic patients (92.2 vs 94.4) using a combination regimen of NS5A and NS5B inhibitors.The systematic review of the literature provided data of 3311 patients: The mean weighted SVR12 rate was 84.4% (CI: 80.4-87.8); the rates varied from 79.0% (CI: 70.9-85.3) with sofosbuvir/ribavirin, to 83.7% (CI: 66.2-93.1) with sofosbuvir/ledispavir, and to 88.2% (CI: 83.3-91.7) with sofosbuvir/daclatasvir.Our results reinforce the concept that patients with HCV genotype 3 should no longer be considered difficult-to-treat individuals. The optimal therapeutic regimen for these patients appears to be the combination sofosbuvir/daclatasvir, administered for 12 weeks without the use of RBV in non-cirrhotic patients. In cirrhotics the meta-analytic approach suggests extending therapy to 24 weeks.

Published
2017

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