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18. Impaired Ribosomal Biogenesis by Noncanonical Degradation of β-Catenin during Hyperammonemia

Author

Davuluri, Gangarao, primary, Giusto, Michela, additional, Chandel, Rajeev, additional, Welch, Nicole, additional, Alsabbagh, Khaled, additional, Kant, Sashi, additional, Kumar, Avinash, additional, Kim, Adam, additional, Gangadhariah, Mahesha, additional, Ghosh, Prabar K., additional, Tran, Uyen, additional, Krajcik, Daniel M., additional, Vasu, Kommireddy, additional, DiDonato, Anthony J., additional, DiDonato, Joseph A., additional, Willard, Belinda, additional, Monga, Satdarshan P., additional, Wang, Yuxin, additional, Fox, Paul L., additional, Stark, George R., additional, Wessely, Oliver, additional, Esser, Karyn A., additional, and Dasarathy, Srinivasan, additional

Published
2019
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19. Prevalent use of combined prophylaxis of hepatitis B after liver transplantation in Italy: results of a national survey in a large cohort

Author

Marzano, Alfredo, Andreone, Pietro, Boccagni, Patrizia, Burra, Patrizia, Caneschi, Francesco, Conoscitore, Pasquale F., Coppola, Carmine, De Carlis, Luciano, Fagiuoli, Stefano, Forte, Paolo, Gaeta, Giovanni B., Iemmolo, Rosa M., Suffredini, Anna Lotti, Mazzola, Michele, Merli, Manuela, Parrilli, Gianpaolo, Piai, Guido, Piras, Maria R., Salizzoni, Mauro, Tamè, Mariarosa, Tisone, Giuseppe, Toniutto, Pierluigi, Vennarecci, Giovanni, Volpes, Riccardo, Zamboni, Fausto, Caccamo, Lucio, Bertuzzo, Valentina R., Bongiovanni, Assunta S., Brin-Dicci, Gaetano, Cocchis, Donatella, Ettorre, Giuseppe M., Gianni, Elena, Giusto, Michela, Lenisa, Ilaria, Lucà, Maria G., Mameli, Laura, Mangoni, Iacopo, Manini, Matteo A., Paoli, Serena, Russo, Francesco P., Staiano, Laura, Stornaiuolo, Gianfranca, Toti, Luca, Valente, Giovanna, Vukotic, Ranka, Ispheb, Group, Marzano, Alfredo, Andreone, Pietro, Boccagni, Patrizia, Burra, Patrizia, Caneschi, Francesco, Conoscitore, Pasquale F, Coppola, Carmine, DE Carlis, Luciano, Fagiuoli, Stefano, Forte, Paolo, Gaeta, Giovanni B, Iemmolo, Rosa M, Lotti Suffredini, Anna, Mazzola, Michele, Merli, Manuela, Parrilli, Gianpaolo, Piai, Guido, Piras, Maria R, Salizzoni, Mauro, Tamè, Mariarosa, Tisone, Giuseppe, Toniutto, Pierluigi, Vennarecci, Giovanni, Volpes, Riccardo, Zamboni, Fausto, Caccamo, Lucio, Marzano, A, Andreone, P, Boccagni, P, Burra, P, Caneschi, F, Conoscitore, P, Coppola, C, De Carlis, L, Fagiuoli, S, Forte, P, Gaeta, G, Iemmolo, R, Suffredini, A, Mazzola, M, Merli, M, Parrilli, G, Piai, G, Piras, M, Salizzoni, M, Tamè, M, Tisone, G, Toniutto, P, Vennarecci, G, Volpes, R, Zamboni, F, Caccamo, L, Bertuzzo, V, Bongiovanni, A, Brin-Dicci, G, Cocchis, D, Ettorre, G, Gianni, E, Giusto, M, Lenisa, I, Lucà, M, Mameli, L, Mangoni, I, Manini, M, Paoli, S, Russo, F, Staiano, L, Stornaiuolo, G, Toti, L, Valente, G, and Vukotic, R

Subjects
0106 biological sciences, Prophylaxis reinfection, Hepatitis B virus-liver transplantation, Immunoglobulins, Chemoprevention, Health Care Surveys, Hepatitis B, Hepatitis B Core Antigens, Humans, Italy, Postoperative Complications, Practice Patterns, Physicians', Retrospective Studies, Tissue Donors, Liver Transplantation, Internal Medicine, Endocrinology, Diabetes and Metabolism, Nutrition and Dietetics, Gastroenterology, medicine.medical_treatment, Practice Patterns, Liver transplantation, 01 natural sciences, 0302 clinical medicine, Endocrinology, Epidemiology, Nutrition and Dietetic, Hepatitis B virus, virus diseases, Entecavir, Diabetes and Metabolism, Hepatocellular carcinoma, Coinfection, 030211 gastroenterology & hepatology, medicine.drug, medicine.medical_specialty, Virus, 03 medical and health sciences, 010608 biotechnology, Internal medicine, medicine, Immunoglobulin, Liver Transplantation, Hepatitis B, Prophylaxis reinfection, Physicians', business.industry, Retrospective cohort study, medicine.disease, digestive system diseases, Settore MED/18, business
Abstract

BACKGROUND Prophylaxis of hepatitis B after liver transplantation with antiviral(s) and immunoglobulins efficiently protect the majority of recipients; however recent experiences suggest a decline of HBsAg-positive candidates and the use of hepatitis B Immunoglobulin-free schedules. METHODS This national survey evaluated the epidemiology and clinical results of hepatitis B prophylaxis among 10,365 liver transplants performed in 25 years in 13 Italian centers. RESULTS With a percentage of 22, 2260 procedures were performed in HBsAg-positive recipients and 714 out of 1080 anti-HBc-positive grafts were used in HBsAg-negative recipients; a total of 2974 patients (29%) were considered at risk of hepatitis B after liver transplantation. Similar rates (18% of HBsAg-positive candidates and 15% of anti-HBc-positive grafts) were registered in the last collected year. Combined prophylaxis with Hepatitis B Immunoglobulins remained prevalent among centers and was effective in 96% of HBsAg-positive recipients and in 94% of HBsAg-negative recipients of anti-HBc-positive grafts. CONCLUSIONS Data from this survey confirm: the excellent results of combined prophylaxis; the past and persistent use of Hepatitis B Immunoglobulin-on and only rare -off prophylactic regimens, in contrast with the newest reports; the increasing use of anti-HBc-positive grafts; the past and present high prevalence of HBsAg-positive recipients, due to an increase in candidates with either hepatocellular carcinoma and Hepatitis Delta Virus coinfection in the last years.

Published
2018

20. Prevalent use of Combined Prophylaxis of Hepatitis B after liver transplantation in Italy: Results of a national survey in a large cohort

Author

Marzano, A, Andreone, P, Boccagni, P, Burra, P, Caneschi, F, Conoscitore, P, Coppola, C, De Carlis, L, Fagiuoli, S, Forte, P, Gaeta, G, Iemmolo, R, Suffredini, A, Mazzola, M, Merli, M, Parrilli, G, Piai, G, Piras, M, Salizzoni, M, Tamè, M, Tisone, G, Toniutto, P, Vennarecci, G, Volpes, R, Zamboni, F, Caccamo, L, Bertuzzo, V, Bongiovanni, A, Brin-Dicci, G, Cocchis, D, Ettorre, G, Gianni, E, Giusto, M, Lenisa, I, Lucà, M, Mameli, L, Mangoni, I, Manini, M, Paoli, S, Russo, F, Staiano, L, Stornaiuolo, G, Toti, L, Valente, G, Vukotic, R, Marzano, Alfredo, Andreone, Pietro, Boccagni, Patrizia, Burra, Patrizia, Caneschi, Francesco, Conoscitore, Pasquale F., Coppola, Carmine, De Carlis, Luciano, Fagiuoli, Stefano, Forte, Paolo, Gaeta, Giovanni B., Iemmolo, Rosa M., Suffredini, Anna Lotti, Mazzola, Michele, Merli, Manuela, Parrilli, Gianpaolo, Piai, Guido, Piras, Maria R., Salizzoni, Mauro, Tamè, Mariarosa, Tisone, Giuseppe, Toniutto, Pierluigi, Vennarecci, Giovanni, Volpes, Riccardo, Zamboni, Fausto, Caccamo, Lucio, Bertuzzo, Valentina R., Bongiovanni, Assunta S., Brin-Dicci, Gaetano, Cocchis, Donatella, Ettorre, Giuseppe M., Gianni, Elena, Giusto, Michela, Lenisa, Ilaria, Lucà, Maria G., Mameli, Laura, Mangoni, Iacopo, Manini, Matteo A., Paoli, Serena, Russo, Francesco P., Staiano, Laura, Stornaiuolo, Gianfranca, Toti, Luca, Valente, Giovanna, Vukotic, Ranka, Marzano, A, Andreone, P, Boccagni, P, Burra, P, Caneschi, F, Conoscitore, P, Coppola, C, De Carlis, L, Fagiuoli, S, Forte, P, Gaeta, G, Iemmolo, R, Suffredini, A, Mazzola, M, Merli, M, Parrilli, G, Piai, G, Piras, M, Salizzoni, M, Tamè, M, Tisone, G, Toniutto, P, Vennarecci, G, Volpes, R, Zamboni, F, Caccamo, L, Bertuzzo, V, Bongiovanni, A, Brin-Dicci, G, Cocchis, D, Ettorre, G, Gianni, E, Giusto, M, Lenisa, I, Lucà, M, Mameli, L, Mangoni, I, Manini, M, Paoli, S, Russo, F, Staiano, L, Stornaiuolo, G, Toti, L, Valente, G, Vukotic, R, Marzano, Alfredo, Andreone, Pietro, Boccagni, Patrizia, Burra, Patrizia, Caneschi, Francesco, Conoscitore, Pasquale F., Coppola, Carmine, De Carlis, Luciano, Fagiuoli, Stefano, Forte, Paolo, Gaeta, Giovanni B., Iemmolo, Rosa M., Suffredini, Anna Lotti, Mazzola, Michele, Merli, Manuela, Parrilli, Gianpaolo, Piai, Guido, Piras, Maria R., Salizzoni, Mauro, Tamè, Mariarosa, Tisone, Giuseppe, Toniutto, Pierluigi, Vennarecci, Giovanni, Volpes, Riccardo, Zamboni, Fausto, Caccamo, Lucio, Bertuzzo, Valentina R., Bongiovanni, Assunta S., Brin-Dicci, Gaetano, Cocchis, Donatella, Ettorre, Giuseppe M., Gianni, Elena, Giusto, Michela, Lenisa, Ilaria, Lucà, Maria G., Mameli, Laura, Mangoni, Iacopo, Manini, Matteo A., Paoli, Serena, Russo, Francesco P., Staiano, Laura, Stornaiuolo, Gianfranca, Toti, Luca, Valente, Giovanna, and Vukotic, Ranka

Abstract

BACKGROUND: Prophylaxis of hepatitis B after liver transplantation with antiviral(s) and immunoglobulins effciently protect the majority of recipients; however recent experiences suggest a decline of HBsag-positive candidates and the use of hepatitis B immunoglobulin-free schedules. MetHoDs: this national survey evaluated the epidemiology and clinical results of hepatitis B prophylaxis among 10,365 liver transplants performed in 25 years in 13 italian centers. RESULTS: With a percentage of 22, 2260 procedures were performed in HBsAg-positive recipients and 714 out of 1080 anti-HBc-positive grafts were used in HBsag-negative recipients; a total of 2974 patients (29%) were considered at risk of hepatitis B after liver transplantation. similar rates (18% of HBsag-positive candidates and 15% of anti-HBc-positive grafts) were registered in the last collected year. combined prophylaxis with Hepatitis B immunoglobulins remained prevalent among centers and was effective in 96% of HBsag-positive recipients and in 94% of HBsag-negative recipients of anti-HBc-positive grafts. CONCLUSIONS: Data from this survey confrm: the excellent results of combined prophylaxis; the past and persistent use of Hepatitis B immunoglobulin-on and only rare-off prophylactic regimens, in contrast with the newest reports; the increasing use of anti-HBc-positive grafts; the past and present high prevalence of HBsag-positive recipients, due to an increase in candidates with either hepatocellular carcinoma and Hepatitis Delta Virus coinfection in the last years

Published
2018

21. Chronic Kidney Disease After Liver Transplantation

Author

Giusto, Michela, Marina, Berenguer, Carlo, Merkel, Victoria, Aguilera, Angel, Rubin, GINANNI CORRADINI, Stefano, Stefano Ginanni Corradini, Mennini, Gianluca, Rossi, Massimo, Martin, Prieto, and Merli, Manuela

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Renal function, Liver transplantation, urologic and male genital diseases, Risk Factors, Internal medicine, Humans, Medicine, Cumulative incidence, Prospective Studies, Renal Insufficiency, Chronic, Risk factor, Aged, Proportional Hazards Models, Transplantation, business.industry, Proportional hazards model, liver transplantation, prediction, mdrd, chronic kidney disease, prognosis, Incidence, Hazard ratio, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Liver Transplantation, surgical procedures, operative, Female, business, Follow-Up Studies, Glomerular Filtration Rate, Kidney disease
Abstract

Background Chronic renal impairment is an emerging problem in the management of patients after liver transplantation (LT). Methods We prospectively analyzed predictors of chronic kidney disease (CKD) after LT in 179 patients followed for a median of 63 months. Diagnosis of CKD was based on an estimated glomerular filtration rate (GFR) of less than 60 mL/min according to the current position statement from the Kidney Disease Improving Global Outcome. Pretransplantation risk factors were evaluated. A Cox regression analysis, with time-dependent variables evaluated during follow-up, was applied to realize a prognostic model for CKD, and a prognostic index was also calculated. The validity of the model was tested in 149 independent LT patients with a median follow-up of 46 months. Results The cumulative incidence of CKD was 45% at 5 years after LT. Estimated GFR at LT was the only pretransplantation independent risk factor (beta, 0.33; standard error (beta), 0.07; 95% confidence interval, 0.95-0.98). Development of arterial hypertension (hazards ratio [HR], 1.83), episodes of severe infection (HR, 2.15), and estimated GFR (HR, 0.89) after LT were identified as independent prognostic factors at the Cox regression time-dependent analysis. The model was able to identify the patients at higher risk for the development of CKD in the validation set. Conclusions Lower renal function at transplantation is associated with a higher risk of CKD after transplantation. A predictive model based on the variation of posttransplantation variables during the course of follow-up can help the clinicians to estimate the probability of CKD in the next 12 months.

Published
2013
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23. Skeletal muscle myopenia in mice model of bile duct ligation and carbon tetrachloride-induced liver cirrhosis

Author

Giusto, Michela, primary, Barberi, Laura, additional, Di Sario, Francesca, additional, Rizzuto, Emanuele, additional, Nicoletti, Carmine, additional, Ascenzi, Francesca, additional, Renzi, Anastasia, additional, Caporaso, Nicola, additional, D'Argenio, Giuseppe, additional, Gaudio, Eugenio, additional, Musarò, Antonio, additional, and Merli, Manuela, additional

Published
2017
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24. Impaired Ribosomal Biogenesis by Non-Canonical Degradation of β-catenin during Hyperammonemia.

Author

Davuluri, Gangarao, Giusto, Michela, Chandel, Rajeev, Welch, Nicole, Alsabbagh, Khaled, Kant, Sashi, Kumar, Avinash, Kim, Adam, Gangadhariah, Mahesha, Ghosh, Prabar K., Tran, Uyen, Krajcik, Daniel M., Vasu, Kommireddy, DiDonato, Anthony J., DiDonato, Joseph, Willard, Belinda, Monga, Satdarshan P., Yuxin Wang, Fox, Paul L., and Stark, George R.

Subjects
*HYPERAMMONEMIA, *ORGANELLE formation, *RIBOSOMAL proteins, *PROTEIN synthesis, *WNT proteins, *PROTEIN-protein interactions, *SKELETAL muscle, *CATENINS
Abstract

Increased ribosomal biogenesis occurs during tissue hypertrophy but whether ribosomal biogenesis is impaired during atrophy is not known. We show that hyperammonemia, which occurs in diverse chronic disorders, impairs protein synthesis as a result of decreased ribosomal content and translational capacity. Transcriptome analyses, real-time PCR and immunoblots showed consistent reduction in expression of the large and small ribosomal protein subunits (RPL, RPS) in hyperammonemic murine skeletal myotubes, HEK cells, and skeletal muscle from hyperammonemic rats and human cirrhotics. Decreased ribosomal content was accompanied by decreased expression of cMYC, a positive regulator of ribosomal biogenesis, as well as reduced expression and activity of β-catenin, a transcriptional activator of cMYC. However, unlike the canonical regulation of β-catenin via GSK3β-dependent degradation, GSK3β expression and phosphorylation were unaltered during hyperammonemia, and depleting GSK3β did not prevent ammonia-induced degradation of β-catenin. Overexpression of GSK3β-resistant variants, genetic depletion of IKKβ (activated during hyperammonemia), protein interactions and in vitro kinase assays showed that IKKβ phosphorylated β-catenin directly. Overexpressing β-catenin restored hyperammonemia-induced perturbations in signaling responses that regulate ribosomal biogenesis. Our data show that decreased protein synthesis during hyperammonemia is mediated via a novel GSK3β-independent, IKKβ-dependent impairment of the β-catenin-cMYC axis. [ABSTRACT FROM AUTHOR]

Published
2019
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34. Ribavirin Transporter [Ent1] Polymorphism is a Pretreatment Predictor of Virologic Response: The Specific Role of Donor Liver Transporter

Author

Giannelli, Valerio, primary, Simmaco, Maurizio, additional, Lionetto, Luana, additional, Gentile, Giovanna, additional, Giusto, Michela, additional, Ponziani, Francesca Romana, additional, Gasbarrini, Antonio, additional, Comandini, Ubaldo Visco, additional, Pellicelli, Adriano, additional, Corradini, Stefano Ginanni, additional, Molinaro, Antonio, additional, Biliotti, Elisa, additional, Merli, Manuela, additional, and Taliani, Gloria, additional

Published
2016
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36. Bone disorders in patients with chronic liver disease awaiting liver transplantation

Author

Loria, I., Albanese, CARLINA VENERANDA, Giusto, Michela, Galtieri, P. A., Giannelli, Valerio, Lucidi, C., Di Menna, S., Pirazzi, C., GINANNI CORRADINI, Stefano, Corradini, S. G., Mennini, Gianluca, Rossi, Massimo, Berloco, Pasquale Bartolomeo, and Merli, Manuela

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, liver trnsplantation, Bone density, Waiting Lists, medicine.medical_treatment, Osteoporosis, osteoporosis, liver trnsplantation, chronic liver disease, Liver transplantation, Chronic liver disease, Gastroenterology, Bone and Bones, Liver disease, Fractures, Bone, Absorptiometry, Photon, Bone Density, Internal medicine, medicine, Humans, Osteodystrophy, Transplantation, business.industry, Liver Diseases, chronic liver disease, medicine.disease, osteoporosis, Liver Transplantation, Osteopenia, Postmenopause, Bone Diseases, Metabolic, Surgery, Female, Bone Diseases, business
Abstract

Background An important complication of chronic liver disease is osteodystrophy, which includes osteoporosis and the much rarer osteomalacia. Both conditions are associated with significant morbidity through fractures resulting in pain, deformity, and immobility. Liver transplantation may further deteriorate bone metabolism. The aim of the present study was to investigate the frequency and severity of hepatic osteodystrophy among patients with liver cirrhosis who were referred for liver transplantation. We also evaluated modifications in bone metabolism after liver transplantation. Materials and methods We recruited 35 consecutive patients with chronic liver disease who were undergoing assessment for transplantation over a 1-year period. Bone mass in the total skeleton and proximal hip was evaluated using a dual-energy X-ray absorptiometry device (Lunar Prodigy Advance, GE Healthcare, USA). According to World Health Organization recommendations, osteoporosis was defined as a T score Results We enrolled in the study 35 patients, including 8 females and 27 males of overall mean age of 57 ± 7, who showed a viral etiology (57%) or alcohol etiology (28%), Child-Pugh 8.7 ± 2.3. The overall prevalence of osteodystrophy was 40% (26% osteopenia and 14% osteoporosis). No difference was evident according to gender, severity of liver disease (Child-Pugh, Model for End-stage Liver Disease), or origin of liver disease. A subgroup of 10 transplanted patients reached 3-month follow-up, showing total body T score with a significant decrease after 3 months while femoral T scores tended to decrease insignificantly. Conclusions This study revealed a high prevalence of low bone mineral density among cirrhotic patients before liver transplantation. We suggest that both bone mineral density and biochemical examinations should be considered to be routine tests to identify the status of bone mass and bone metabolism among recipients prior to liver transplantation.

Published
2010

37. The Spread of Multi Drug Resistant Infections Is Leading to an Increase in the Empirical Antibiotic Treatment Failure in Cirrhosis: A Prospective Survey

Author

Merli, Manuela, primary, Lucidi, Cristina, additional, Di Gregorio, Vincenza, additional, Falcone, Marco, additional, Giannelli, Valerio, additional, Lattanzi, Barbara, additional, Giusto, Michela, additional, Ceccarelli, Giancarlo, additional, Farcomeni, Alessio, additional, Riggio, Oliviero, additional, and Venditti, Mario, additional

Published
2015
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38. Sarcopenia in liver cirrhosis

Author

Giusto, Michela, primary, Lattanzi, Barbara, additional, Albanese, Carlina, additional, Galtieri, Alessia, additional, Farcomeni, Alessio, additional, Giannelli, Valerio, additional, Lucidi, Cristina, additional, Di Martino, Michele, additional, Catalano, Carlo, additional, and Merli, Manuela, additional

Published
2015
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