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1. Hepatitis B virus reactivation sustained by a hepatitis B virus surface antigen immune-escape mutant isolate in a patient who was hepatitis B core antibody positive during treatment with sofosbuvir and velpatasvir for hepatitis C virus infection: a case report

Author

Luca Foroghi Biland, Ludovica Ferrari, Vincenzo Malagnino, Elisabetta Teti, Carlotta Cerva, Adele Gentile, Marianna Aragri, Romina Salpini, Valentina Svicher, Massimo Andreoni, and Loredana Sarmati

Subjects
Hepatitis B virus, HBV reactivation, Direct acting antivirals, Coinfection HBV/HCV, Immune-escape HBV mutant, Medicine
Abstract

Abstract Background Although several cases of hepatitis B virus reactivation have been described in patients with a history of hepatitis B virus infection while undergoing treatment for hepatitis C virus infection with direct acting antivirals, the question of whether hepatitis B virus surface antigen immune-escape mutations might play a role has not been addressed so far. Case presentation We report a case of hepatitis B virus reactivation in a Caucasian patient infected with hepatitis C virus during treatment with sofosbuvir and velpatasvir. A 50-year-old man with a genotype 1a hepatitis C virus infection was considered for therapy. His serological profile was hepatitis B virus surface antigen-negative, hepatitis B virus core antibody-positive, hepatitis B virus surface antibody-negative, and anti-hepatitis D virus-positive. The detection of hepatitis B virus deoxyribonucleic acid (DNA) indicated active viral replication during the direct acting antiviral treatment that spontaneously returned to undetectable levels after treatment completion. Starting from week 12 after the end of treatment, hepatitis B virus surface antibody titers and hepatitis B virus e antibody developed. Sequencing analysis revealed the hepatitis B virus genotype D3 and the presence of two relevant immune-escape mutations (P120S and T126I) in the major hydrophilic region by analyzing the S region. Conclusions We speculate that the presence of the hepatitis B virus surface antigen mutations, endowed with the enhanced capability to elude the immune response, could play a role in hepatitis B virus reactivation. This observation confirms that occult hepatitis B infection should also be carefully monitored, through surveillance of the hepatitis B virus viral load before and during direct acting antiviral treatment of hepatitis C virus.

Published
2019
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2. Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C

Author

Di Maio, V. C., Barbaliscia, S., Teti, E., Fiorentino, G., Milana, M., Paolucci, S., Pollicino, T., Morsica, G., Starace, M., Bruzzone, B., Gennari, W., Micheli, V., Yu La Rosa, K., Foroghi, L., Calvaruso, V., Lenci, I., Polilli, E., Babudieri, S., Aghemo, A., Raimondo, G., Sarmati, L., Coppola, N., Pasquazzi, C., Baldanti, F., Parruti, G., Perno, C. F., Angelico, M., Craxi, A., Andreoni, M., Ceccherini-Silberstein, F., Andreone, P., Aragri, M., Bertoli, A., Boeri, E., Brancaccio, G., Brunetto, M., Callegaro, A. P., Cenderello, G., Cento, V., Ciaccio, A., Ciancio, A., Cuomo, N., De Santis, A., Di Biagio, A., Di Marco, V., Di Perri, G., Di Stefano, M. A., Gaeta, G. B., Ghisetti, V., Gulminetti, R., Lampertico, P., Landonio, S., Lichtner, M., Lleo, A., Maida, I., Marenco, S., Masetti, C., Mastroianni, C., Minichini, C., Milano, E., Monno, L., Novati, S., Pace Palitti, V., Paternoster, C., Pellicelli, A., Pieri, A., Puoti, M., Rizzardini, G., Ruggiero, T., Rossetti, B., Sangiovanni, V., Santantonio, T., Taliani, G., Toniutto, P., Vullo, V., Zazzi, M., Di Maio, V, Barbaliscia, S, Teti, E, Fiorentino, G, Milana, M, Paolucci, S, Pollicino, T, Morsica, G, Starace, M, Bruzzone, B, Gennari, W, Micheli, V, Yu La Rosa, K, Foroghi, L, Calvaruso, V, Lenci, I, Polilli, E, Babudieri, S, Aghemo, A, Raimondo, G, Sarmati, L, Coppola, N, Pasquazzi, C, Baldanti, F, Parruti, G, Perno, C, Angelico, M, Craxi, A, Andreoni, M, Ceccherini-Silberstein, F, Andreone, P, Aragri, M, Bertoli, A, Boeri, E, Brancaccio, G, Brunetto, M, Callegaro, A, Cenderello, G, Cento, V, Ciaccio, A, Ciancio, A, Cuomo, N, De Santis, A, Di Biagio, A, Di Marco, V, Di Perri, G, Di Stefano, M, Gaeta, G, Ghisetti, V, Gulminetti, R, Lampertico, P, Landonio, S, Lichtner, M, Lleo, A, Maida, I, Marenco, S, Masetti, C, Mastroianni, C, Minichini, C, Milano, E, Monno, L, Novati, S, Pace Palitti, V, Paternoster, C, Pellicelli, A, Pieri, A, Puoti, M, Rizzardini, G, Ruggiero, T, Rossetti, B, Sangiovanni, V, Santantonio, T, Taliani, G, Toniutto, P, Vullo, V, Zazzi, M, Di Maio, Vc, Perno, Cf, Craxì, A, Di Maio V.C., Barbaliscia S., Teti E., Fiorentino G., Milana M., Paolucci S., Pollicino T., Morsica G., Starace M., Bruzzone B., Gennari W., Micheli V., Yu La Rosa K., Foroghi L., Calvaruso V., Lenci I., Polilli E., Babudieri S., Aghemo A., Raimondo G., Sarmati L., Coppola N., Pasquazzi C., Baldanti F., Parruti G., Perno C.F., Angelico M., Craxi A., Andreoni M., Ceccherini-Silberstein F., Andreone P., Aragri M., Bertoli A., Boeri E., Brancaccio G., Brunetto M., Callegaro A.P., Cenderello G., Cento V., Ciaccio A., Ciancio A., Cuomo N., De Santis A., Di Biagio A., Di Marco V., Di Perri G., Di Stefano M.A., Gaeta G.B., Ghisetti V., Gulminetti R., Lampertico P., Landonio S., Lichtner M., Lleo A., Maida I., Marenco S., Masetti C., Mastroianni C., Minichini C., Milano E., Monno L., Novati S., Pace Palitti V., Paternoster C., Pellicelli A., Pieri A., Puoti M., Rizzardini G., Ruggiero T., Rossetti B., Sangiovanni V., Santantonio T., Taliani G., Toniutto P., Vullo V., and Zazzi M.

Subjects
Male, Sofosbuvir, Sustained Virologic Response, Drug Resistance, Hepacivirus, Viral Nonstructural Proteins, Gastroenterology, Settore MED/06, direct-acting antivirals, failure, genotype 3, HCV, resistance, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Viral, Chronic, Phylogeny, Dasabuvir, hcv, virus diseases, Hepatitis C, Pibrentasvir, Italy, 030220 oncology & carcinogenesis, Combination, Drug Therapy, Combination, 030211 gastroenterology & hepatology, Female, medicine.drug, Ledipasvir, medicine.medical_specialty, Daclatasvir, Genotype, Antiviral Agents, Drug Resistance, Viral, Humans, Hepatitis C, Chronic, 03 medical and health sciences, Drug Therapy, Internal medicine, Antiviral Agent, direct-acting antiviral, Hepaciviru, Hepatology, business.industry, Viral Nonstructural Protein, Glecaprevir, direct acting antivirals, Regimen, chemistry, Paritaprevir, business
Abstract

Aim: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols. Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N=91/15) and glecaprevir (G)/pibrentasvir (P) (N=9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D±RBV (Paritaprevir/r+Ombitasvir+Dasabuvir, N=15), SOF+Simeprevir (SIM) (N=1) or SOF/Ledipasvir (LDV)±RBV (N=4). RAS prevalence was 15.8% in DAA-naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF-failures. In NS5A-failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA-naïve, P&nbsp

Published
2021

3. Phylogenetic analysis in the clinical risk management of an outbreak of hepatitis C virus infection among transfused thalassaemia patients in Italy

Author

Stefania Grimaudo, Francesca Ceccherini-Silberstein, Lavinia Fabeni, V. Di Marco, Marianna Aragri, F. Di Raimondo, Claudia Marotta, Mazzucco W, Fabrizio Bronte, Maurizio Macaluso, Francesco Vitale, V. Chiara di Maio, Donatella Ferraro, Rosaria Maria Pipitone, Mazzucco W., Chiara di Maio V., Bronte F., Fabeni L., Pipitone R.M., Grimaudo S., Ferraro D., Marotta C., Aragri M., Macaluso M., Vitale F., Di Raimondo F., Ceccherini-Silberstein F., and Di Marco V.

Subjects
Sofosbuvir, Clinical risk management, Hepatitis C virus (HCV), Molecular epidemiology, Nosocomial outbreak, Phylogenetic analysis, Antiviral Agents, Bayes Theorem, Disease Outbreaks, Genotype, Hepacivirus, Humans, Italy, Phylogeny, Risk Management, Hepatitis C, Thalassemia, Hepacivirus, 030501 epidemiology, Settore MED/42 - Igiene Generale E Applicata, medicine.disease_cause, Disease Outbreaks, Settore MED/07, chemistry.chemical_compound, Settore BIO/13 - Biologia Applicata, Epidemiology, Medicine, Phylogeny, Settore MED/12 - Gastroenterologia, 0303 health sciences, Clinical risk management, Phylogenetic analysis, biology, Transmission (medicine), virus diseases, General Medicine, Hepatitis C, Hepatitis C virus (HCV), Infectious Diseases, Italy, Molecular epidemiology, Thalassemia, 0305 other medical science, medicine.drug, Microbiology (medical), Ledipasvir, medicine.medical_specialty, Genotype, Hepatitis C virus, Antiviral Agents, 03 medical and health sciences, Phylogenetic analysi, Internal medicine, Humans, Risk Management, 030306 microbiology, business.industry, Nosocomial outbreak, Bayes Theorem, biology.organism_classification, medicine.disease, digestive system diseases, Chronic infection, chemistry, business
Abstract

Background: Occurrence of hepatitis C virus (HCV) infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings. Aim: To report the use of phylogenetic analysis in the clinical risk management of an HCV outbreak among 128 thalassaemia outpatients followed at a thalassaemia centre of an Italian hospital. Methods: Epidemiological investigation and root-cause analysis were performed. All patients with acute hepatitis and known chronic infection were tested for HCV RNA, HCV genotyping, and NS3, NS5A, and NS5B HCV genomic region sequencing. To identify transmission clusters, phylogenetic trees were built for each gene employing Bayesian methods. Findings: All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, excluded blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response. Conclusion: Combined use of root-cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment.

Published
2021

4. A hyper-glycosylation of HBV surface antigen correlates with HBsAg-Negativity at immunosuppression-driven HBV reactivation in vivo and hinders HBsAg recognition in vitro

Author

Francesca Ceccherini-Silberstein, Carlotta Cerva, Ada Bertoli, Carlo Federico Perno, Massimo Marignani, Miriam Lichtner, Aldo Marrone, L. Colagrossi, Jens Verheyen, Valentina Svicher, Katia Yu La Rosa, N. Iapadre, Constance Delaugerre, L. Piermatteo, Massimo Levrero, Sarah Maylin, Marianna Aragri, Nicola Coppola, Loredana Sarmati, Stefano Aquaro, A. Battisti, Romina Salpini, Laura Belloni, Massimo Andreoni, Mario Angelico, Patrizia Saccomandi, Filomena Morisco, Salpini, R., Piermatteo, L., Battisti, A., Colagrossi, L., Aragri, M., Rosa, K. Y. L., Bertoli, A., Saccomandi, P., Lichtner, M., Marignani, M., Maylin, S., Delaugerre, C., Morisco, F., Coppola, N., Marrone, A., Iapadre, N., Cerva, C., Aquaro, S., Angelico, M., Sarmati, L., Andreoni, M., Verheyen, J., Ceccherini-Silberstein, F., Levrero, M., Perno, C. F., Belloni, L., Svicher, V., Salpini, Romina, Piermatteo, Lorenzo, Battisti, Arianna, Colagrossi, Luna, Aragri, Marianna, Yu La Rosa, Katia, Bertoli, Ada, Saccomandi, Patrizia, Lichtner, Miriam, Marignani, Massimo, Maylin, Sarah, Delaugerre, Constance, Morisco, Filomena, Coppola, Nicola, Marrone, Aldo, Iapadre, Nerio, Cerva, Carlotta, Aquaro, Stefano, Angelico, Mario, Sarmati, Loredana, Andreoni, Massimo, Verheyen, Jen, Ceccherini-Silberstein, Francesca, Levrero, Massimo, Federico Perno, Carlo, Belloni, Laura, and Svicher, Valentina

Subjects
0301 basic medicine, Male, HBsAg, Glycosylation, lcsh:QR1-502, Medizin, medicine.disease_cause, lcsh:Microbiology, HBV, HBV reactivation, N-linked glycosylation, 0302 clinical medicine, biology, virus diseases, Middle Aged, Infectious Diseases, 030211 gastroenterology & hepatology, Female, Antibody, Hepatitis B virus, Article, Cell Line, 03 medical and health sciences, Antigen, In vivo, Virology, medicine, Humans, Hepatitis B Antibodies, Aged, Immune Evasion, Hepatitis, Immunosuppression Therapy, Hepatitis B Surface Antigens, business.industry, medicine.disease, In vitro, Settore MED/17, digestive system diseases, 030104 developmental biology, Reinfection, Mutation, biology.protein, Virus Activation, business
Abstract

Immune-suppression driven Hepatitis B Virus (HBV)-reactivation poses serious concerns since it occurs in several clinical settings and can result in severe forms of hepatitis. Previous studies showed that HBV strains, circulating in patients with HBV-reactivation, are characterized by an enrichment of immune-escape mutations in HBV surface antigen (HBsAg). Here, we focused on specific immune-escape mutations associated with the acquisition of N-linked glycosylation sites in HBsAg (NLGSs). In particular, we investigated profiles of NLGSs in 47 patients with immunosuppression-driven HBV-reactivation and we evaluated their impact on HBsAg-antigenicity and HBV-replication in vitro. At HBV-reactivation, despite a median serum HBV-DNA of 6.7 [5.3&ndash, 8.0] logIU/mL, 23.4% of patients remained HBsAg-negative. HBsAg-negativity at HBV-reactivation correlated with the presence of &gt, 1 additional NLGSs (p &lt, 0.001). These NLGSs are located in the major hydrophilic region of HBsAg (known to be the target of antibodies) and resulted from the single mutation T115N, T117N, T123N, N114ins, and from the triple mutant S113N+T131N+M133T. In vitro, NLGSs strongly alter HBsAg antigenic properties and recognition by antibodies used in assays for HBsAg-quantification without affecting HBsAg-secretion and other parameters of HBV-replication. In conclusion, additional NLGSs correlate with HBsAg-negativity despite HBV-reactivation, and hamper HBsAg-antigenicity in vitro, supporting the role of NGSs in immune-escape and the importance of HBV-DNA for a proper diagnosis of HBV-reactivation.

Published
2020

5. Establishment of a Seronegative Occult Infection With an Active Hepatitis B Virus Reservoir Enriched of Vaccine Escape Mutations in a Vaccinated Infant After Liver Transplantation

Author

Maria Concetta Bellocchi, Paola Francalanci, Rossana Scutari, L. Piermatteo, L. Carioti, Marco Ciotti, Romina Salpini, Maria Sole Basso, Mohammed Alkhatib, Marianna Aragri, Daniela Liccardo, Valentina Svicher, Manila Candusso, and Andrea Pietrobattista

Subjects
0301 basic medicine, Hepatitis B virus, medicine.medical_treatment, Liver transplantation, Virus Replication, medicine.disease_cause, Polymerase Chain Reaction, Virus, hepatitis B occult infection, Settore MED/07, law.invention, HBV reservoir, digital droplet PCR, liver transplantation, vaccine escape mutations, 03 medical and health sciences, 0302 clinical medicine, Antigen, law, medicine, Humans, Immunology and Allergy, Polymerase chain reaction, biology, Transmission (medicine), business.industry, Vaccination, Hepatitis B, Virology, 030104 developmental biology, Infectious Diseases, Liver, Child, Preschool, DNA, Viral, Mutation, biology.protein, Female, 030211 gastroenterology & hepatology, Antibody, business, Biomarkers
Abstract

We describe the establishment of a seronegative occult hepatitis B virus (HBV) infection (OBI) in a successfully vaccinated infant who underwent liver transplantation from an donor positive for antibody to hepatitis B core antigen (anti-HBc). The use of highly sensitive droplet digital polymerase chain reaction assays revealed a not negligible and transcriptionally active intrahepatic HBV reservoir (circular covalently closed DNA, relaxed circular DNA, and pregenomic RNA: 5.6, 2.4, and 1.1 copies/1000 cells, respectively), capable to sustain ongoing viral production and initial liver damage. Next-generation sequencing revealed a peculiar enrichment of hepatitis B surface antigen vaccine-escape mutations that could have played a crucial role in OBI transmission. This clinical case highlights the pathobiological complexity and the diagnostic challenges underlying OBI.

Published
2019
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6. Prevalence of resistance-associated substitutions and retreatment of patients failing a glecaprevir/pibrentasvir regimen

Author

de Salazar, Adolfo, Dietz, Julia, di Maio, Velia Chiara, Vermehren, Johannes, Paolucci, Stefania, Müllhaupt, Beat, Coppola, Nicola, Cabezas, Joaquín, Stauber, Rudolf E, Puoti, Massimo, Arenas Ruiz Tapiador, Juan Ignacio, Graf, Christiana, Aragri, Marianna, Jimenez, Miguel, Callegaro, Annapaola, Pascasio Acevedo, Juan Manuel, Macias Rodriguez, Manuel Alberto, Rosales Zabal, Jose Miguel, Micheli, Valeria, Garcia Del Toro, Miguel, Téllez, Francisco, García, Federico, Sarrazin, Christoph, Ceccherini-Silberstein, Francesca, HCV Virology Italian Resistance Network (VIRONET C), De Santis, Adriano, de Salazar, Adolfo, Dietz, Julia, di Maio, Velia Chiara, Vermehren, Johanne, Paolucci, Stefania, Müllhaupt, Beat, Coppola, Nicola, Cabezas, Joaquín, Stauber, Rudolf E, Puoti, Massimo, Arenas Ruiz Tapiador, Juan Ignacio, Graf, Christiana, Aragri, Marianna, Jimenez, Miguel, Callegaro, Annapaola, Pascasio Acevedo, Juan Manuel, Macias Rodriguez, Manuel Alberto, Rosales Zabal, Jose Miguel, Micheli, Valeria, Garcia Del Toro, Miguel, Téllez, Francisco, García, Federico, Sarrazin, Christoph, Ceccherini-Silberstein, Francesca, and University of Zurich

Subjects
Cyclopropanes, 0301 basic medicine, Aminoisobutyric Acids, Pyrrolidines, Sofosbuvir, viruses, Hepacivirus, Viral Nonstructural Proteins, Settore MED/07, 0302 clinical medicine, Germany, Genotype, Prevalence, Pharmacology (medical), To investigate resistance-associated substitutions (RASs) as well as retreatment efficacies in a large cohort of European patients with failure of glecaprevir/pibrentasvir, Sulfonamides, virus diseases, Pibrentasvir, 10219 Clinic for Gastroenterology and Hepatology, Infectious Diseases, Italy, Retreatment, 030211 gastroenterology & hepatology, medicine.drug, Microbiology (medical), medicine.medical_specialty, Proline, Lactams, Macrocyclic, Voxilaprevir, 610 Medicine & health, Antiviral Agents, 03 medical and health sciences, Leucine, Quinoxalines, Internal medicine, Drug Resistance, Viral, medicine, Humans, NS5A, Retrospective Studies, Pharmacology, business.industry, Glecaprevir, biochemical phenomena, metabolism, and nutrition, digestive system diseases, Regimen, 030104 developmental biology, Spain, Benzimidazoles, business, Velpatasvir
Abstract

Objectives To investigate resistance-associated substitutions (RASs) as well as retreatment efficacies in a large cohort of European patients with failure of glecaprevir/pibrentasvir. Methods Patients were identified from three European Resistance Reference centres in Spain, Italy and Germany. Sequencing of NS3, NS5A and NS5B was conducted and substitutions associated with resistance to direct antiviral agents were analysed. Clinical and virological parameters were documented retrospectively and retreatment efficacies were evaluated. Results We evaluated 90 glecaprevir/pibrentasvir failures [3a (n = 36), 1a (n = 23), 2a/2c (n = 20), 1b (n = 10) and 4d (n = 1)]. Ten patients were cirrhotic, two had previous exposure to PEG-interferon and seven were coinfected with HIV; 80 had been treated for 8 weeks. Overall, 31 patients (34.4%) failed glecaprevir/pibrentasvir without any NS3 or NS5A RASs, 62.4% (53/85) showed RASs in NS5A, 15.6% (13/83) in NS3 and 10% (9/90) in both NS5A and NS3. Infection with HCV genotypes 1a and 3a was associated with a higher prevalence of NS5A RASs. Patients harbouring two (n = 34) or more (n = 8) RASs in NS5A were frequent. Retreatment was initiated in 56 patients, almost all (n = 52) with sofosbuvir/velpatasvir/voxilaprevir. The overall sustained virological response rate was 97.8% in patients with end-of-follow-up data available. Conclusions One-third of patients failed glecaprevir/pibrentasvir without resistance. RASs in NS5A were more prevalent than in NS3 and were frequently observed as dual and triple combination patterns, with a high impact on NS5A inhibitor activity, particularly in genotypes 1a and 3a. Retreatment of glecaprevir/pibrentasvir failures with sofosbuvir/velpatasvir/voxilaprevir achieved viral suppression across all genotypes.

Published
2020

7. An Outbreak of Hepatitis C Virus Infection Among Transfused Thalassemia Patients: Root Cause Analysis, Phylogenetic Epidemiology and Antiviral Therapy

Author

Donatella Ferraro, Walter Mazzucco, Claudia Marotta, Francesco Di Raimondo, Marianna Aragri, Velia Chiara Di Maio, Stefania Grimaudo, Vito Di Marco, Maurizio Macaluso, Lavinia Fabeni, Rosaria Maria Pipitone, Fabrizio Bronte, and Francesca Ceccherini

Subjects
Ledipasvir, medicine.medical_specialty, Blood transfusion, Sofosbuvir, Transmission (medicine), business.industry, Hepatitis C virus, medicine.medical_treatment, medicine.disease_cause, Helsinki declaration, chemistry.chemical_compound, Chronic infection, chemistry, Internal medicine, Epidemiology, medicine, business, medicine.drug
Abstract

Background: Occurrence of HCV infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings. We report an outbreak of 11 patients with HCV acute hepatitis (seven new infections and four re-infections) among 128 thalassemia patients followed at a Hospital in Sicily. Methods All patients with acute hepatitis and known chronic infection were tested for HCV-RNA, HCV genotyping, and NS3, NS5A and NS5B HCV-genomic regions sequencing. To identify transmission clusters we built phylogenetic trees for each gene employing Bayesian methods. Findings All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, led us to exclude blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion at the Thalassemia Unit during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response. Interpretation Combined use of root cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment. Funding Regional Health System of Sicily and by the Italian Ministry of Health (RF-2016-02362422). Declaration of Interest: V.D.M received speaking and/or consulting fees by Abbvie, Gilead, MSD, Intercept. F.C-S. received speaking and/or consulting fees by Abbvie, Gilead, Janssen, Merck/MSD, ViiV . All other authors have nothing to declare. Ethical Approval: This study was conducted in agreement with the Helsinki Declaration. Since the available DAAs were not licensed for acute hepatitis, the regional health authorities and local ethics committee authorized DAA therapy in patients with diagnosis of acute hepatitis

Published
2021
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8. Successful ongoing retreatment with glecaprevir/pibrentasvir + sofosbuvir + ribavirin in a patient with HCV genotype 3 who failed glecaprevir/pibrentasvir with both NS3 and NS5A resistance

Author

Francesca Ceccherini-Silberstein, Carlo Federico Perno, Ilaria Lenci, Martina Milana, Valentina Svicher, Marianna Aragri, Mario Angelico, V.C. Di Maio, and L. Carioti

Subjects
Microbiology (medical), medicine.medical_specialty, Sofosbuvir, business.industry, Ribavirin, General Medicine, Settore MED/07, chemistry.chemical_compound, Infectious Diseases, chemistry, Internal medicine, Genotype, medicine, Glecaprevir / pibrentasvir, business, NS5A, medicine.drug
Published
2020

9. 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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10. Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?

Author

Velia Chiara Di Maio, Valeria Cento, Marianna Aragri, Stefania Paolucci, Teresa Pollicino, Nicola Coppola, Bianca Bruzzone, Valeria Ghisetti, Maurizio Zazzi, Maurizia Brunetto, Ada Bertoli, Silvia Barbaliscia, Silvia Galli, William Gennari, Fausto Baldanti, Giovanni Raimondo, Carlo Federico Perno, Francesca Ceccherini-Silberstein, Pietro Andreone, Massimo Andreoni, Mario Angelico, Sergio Babudieri, Giorgio Barbarini, Vincenzo Boccaccio, Lucio Boglione, Matteo Bolis, Stefano Bonora, Vanni Borghi, Giuseppina Brancaccio, Savino Bruno, Pierluigi Cacciatore, Vincenza Calvaruso, Nicola Caporaso, Antonio Ciaccio, Alessia Ciancio, Piero Colombatto, Raffaele Cozzolongo, Antonio Craxì, Cecilia D'Ambrosio, Gabriella D'Ettorre, Andrea De Luca, Antonio Di Biagio, Giovanni Di Perri, Simona Francioso, Giovanni Battista Gaeta, Alessia Giorgini, Antonio Grieco, Guido Gubertini, Roberto Gulminetti, Lara Lambiase, Ilaria Lenci, Miriam Lichtner, Ivana Maida, Simona Marenco, Letizia Marinaro, Renato Maserati, Chiara Masetti, Michela Melis, Elisa Meregalli, Valeria Micheli, Filomena Morisco, Fosca Niero, Laura Ambra Nicolini, Valeria Pace Palitti, Maurizio Paoloni, Giustino Parruti, Caterina Pasquazzi, Adriano Pellicelli, Ennio Polilli, Maria Laura Ponti, Massimo Puoti, Maria Rendina, Giuliano Rizzardini, Barbara Rossetti, Tina Ruggiero, Vincenzo Sangiovanni, Mario Starace, Laura Sticchi, Pierluigi Tarquini, Pierluigi Toniutto, Vincenzo Vullo, Di Maio VC, Cento V, Aragri M, Paolucci S, Pollicino T3, Coppola N4, Bruzzone B5, Ghisetti V6, Zazzi M7, Brunetto M8, Bertoli A1, Barbaliscia S1, Galli S9, Gennari W10, Baldanti F2, Raimondo G3, Perno CF1, Ceccherini-Silberstein F11, Andreone P, Andreoni M, Angelico M, Babudieri S, Barbarini G, Boccaccio V, Boglione L, Bolis M, Bonora S, Borghi V, Brancaccio G, Bruno S, Cacciatore P, Calvaruso Vincenza, Caporaso N, Ciaccio A, Ciancio A, Colombatto P, Cozzolongo R, Craxì Antonio, D'Ambrosio C, D'Ettorre G, De Luca A, Di Biagio A, Di Perri G, Francioso S, Gaeta GB, Giorgini A, Grieco A, Gubertini G, Gulminetti R, Lambiase L, Lenci I, Lichtner M, Maida I, Marenco S, Marinaro L, Maserati R, Masetti C, Melis M, Meregalli E, Micheli V, Morisco F, Niero F, Nicolini LA, Palitti VP, Paoloni M, Parruti G, Pasquazzi C, Pellicelli A, Polilli E, Ponti ML, Puoti M, Rendina M, Rizzardini G, Rossetti B, Ruggiero T, Sangiovanni V, Starace M, Sticchi L, Tarquini P, Toniutto P, Vullo V., Di Maio, Vc, Cento, V, Aragri, M, Paolucci, S, Pollicino, T, Coppola, N, Bruzzone, B, Ghisetti, V, Zazzi, M, Brunetto, M, Bertoli, A, Barbaliscia, S, Galli, S, Gennari, W, Baldanti, F, Raimondo, G, Perno, Cf, Ceccherini-Silberstein, F., Andreone P, Andreoni, M, Angelico, M, Babudieri, S, Barbarini, G, Boccaccio, V, Boglione, L, Bolis, M, Bonora, S, Borghi, V, Brancaccio, G, Bruno, S, Cacciatore, P, Calvaruso, V, Caporaso, N, Ciaccio, A, Ciancio, A, Colombatto, P, Cozzolongo, R, Craxì, A, D'Ambrosio, C, D'Ettorre, G, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, Gb, Giorgini, A, Grieco, A, Gubertini, G, Gulminetti, R, Lambiase, L, Lenci, I, Lichtner, M, Maida, I, Marenco, S, Marinaro, L, Maserati, R, Masetti, C, Melis, M, Meregalli, E, Micheli, V, Morisco, F, Niero, F, Nicolini, La, Palitti, Vp, Paoloni, M, Parruti, G, Pasquazzi, C, Pellicelli, A, Polilli, E, Ponti, Ml, Puoti, M, Rendina, M, Rizzardini, G, Rossetti, B, Ruggiero, T, Sangiovanni, V, Starace, M, Sticchi, L, Tarquini, P, Toniutto, P, Vullo, V., Di Maio, V, Perno, C, Ceccherini-Silberstein, F, Andreone, P, Craxi, A, Gaeta, G, Nicolini, L, Palitti, V, Ponti, M, and Vullo, V

Subjects
0301 basic medicine, medicine.medical_specialty, hepacivirus, HCV RAS, Treatment outcome, Drug Resistance, HCV genotypes, Drug resistance, Biology, NS5A, 03 medical and health sciences, 0302 clinical medicine, Second line, drug resistance viral, humans, retreatment, treatment outcome, antiviral agents, hepatitis c chronic, Internal medicine, Drug Resistance, Viral, Humans, Retreatment, Treatment Outcome, Antiviral Agents, Hepacivirus, Hepatitis C, Chronic, medicine, Viral, Chronic, Hepatology, Hepatitis C, Settore MED/07 - Microbiologia e Microbiologia Clinica, medicine.disease, Virology, Hepatology, HCV, NS5A, 030104 developmental biology, HCV, 030211 gastroenterology & hepatology
Published
2018

11. 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

12. Optimal cure rate by personalized HCV regimens in real-life: a proof-of-concept study

Author

Ada Bertoli, Valeria Cento, Luca Foroghi, Valeria Pace Palitti, Silvia Barbaliscia, Massimo Andreoni, Alessandro Pieri, Marianna Aragri, Carlo Federico Perno, Francesca Ceccherini-Silberstein, Giustino Parruti, Ennio Polilli, Velia Chiara Di Maio, Loredana Sarmati, and Elisabetta Teti

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Cure rate, Settore MED/17 - Malattie Infettive, Genotype, Sustained Virologic Response, Personalized treatment, Administration, Oral, Context (language use), Hepacivirus, Microbial Sensitivity Tests, Antiviral Agents, Proof of Concept Study, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, In real life, Pharmacology (medical), Precision Medicine, Pharmacology, business.industry, Ribavirin, Sequence Analysis, DNA, Guideline, Hepatitis C, Chronic, Surgery, Discontinuation, Regimen, Treatment Outcome, 030104 developmental biology, Infectious Diseases, chemistry, RNA, Viral, 030211 gastroenterology & hepatology, business
Abstract

Background Pretreatment evaluation of HCV-infected patients is a complex interplay between multiple clinical and viral parameters, leading to a tailored approach that may bring real-life sustained virological response (SVR) rates close to 98%-99%. Objectives As proof-of-concept, we evaluated the efficacy of all-oral direct-acting antiviral (DAA) regimens in patients whose personalization included pre-therapy evaluation of natural resistance-associated substitutions (RASs), in addition to international guideline recommendations. Methods One hundred and thirty-one patients who started a first-line all-oral DAA regimen between April 2015 and December 2016 were tested for baseline NS3 and NS5A RASs by Sanger sequencing. SVR12 was defined as HCV-RNA undetectability 12 weeks after treatment discontinuation. Results Compatibly with a real-life context, 74.0% (97 of 131) of patients presented ≥2 pretreatment risk factors for failure to achieve SVR12 (infection by GT-1a/GT-3a; cirrhosis; previous treatment experience; HCV-RNA ≥800 000 IU/mL) and 33.6% had ≥3 risk factors. Natural RASs were frequently detected (32.1% prevalence), with substantial prevalence of NS5A RASs (15.3%), mostly represented by Y93H in GT-1b (3 of 36, 8.3%) and GT-3a (3 of 25, 12.0%) and F28C in GT-2c (2 of 11, 18.2%). Overall, personalized treatment led to 100% SVR12, even in those patients for whom treatment strategy was either strengthened (by ribavirin inclusion and/or duration increase) or simplified (by ribavirin exclusion and/or duration reduction), thanks to baseline RAS evaluation. Conclusions Even with newer DAA regimens, an integrated interpretation of clinical and virological pretreatment parameters, including natural RASs, may play a relevant role in bringing SVR rates close to the highest achievable. Treatment tailoring can be foreseen in 'hard-to-treat' patients, but also in 'easy' patients with favourable indicators, whereby a simplification/shortening of recommended regimens can be indicated.

Published
2017
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13. Hepatitis B virus reactivation sustained by a hepatitis B virus surface antigen immune-escape mutant isolate in a patient who was hepatitis B core antibody positive during treatment with sofosbuvir and velpatasvir for hepatitis C virus infection: A case report

Author

Valentina Svicher, Carlotta Cerva, Romina Salpini, Massimo Andreoni, Loredana Sarmati, Adele Gentile, Ludovica Ferrari, Marianna Aragri, Vincenzo Malagnino, Elisabetta Teti, and Luca Foroghi Biland

Subjects
0301 basic medicine, Male, Hepatitis B virus, Sofosbuvir, Genotype, Settore MED/17 - Malattie Infettive, Hepatitis C virus, viruses, HBV reactivation, lcsh:Medicine, Coinfection HBV/HCV, Case Report, medicine.disease_cause, Antiviral Agents, Heterocyclic Compounds, 4 or More Rings, Direct acting antivirals, Serology, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Hepatitis B Antibodies, Immune-escape HBV mutant, Hepatitis B Virus Surface Antibody, Hepatitis B Surface Antigens, business.industry, Coinfection, lcsh:R, General Medicine, Hepatitis C, Chronic, Middle Aged, Hepatitis B, Virology, Titer, 030104 developmental biology, Viral replication, Mutation, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Virus Activation, Carbamates, business, Viral load, medicine.drug
Abstract

Background Although several cases of hepatitis B virus reactivation have been described in patients with a history of hepatitis B virus infection while undergoing treatment for hepatitis C virus infection with direct acting antivirals, the question of whether hepatitis B virus surface antigen immune-escape mutations might play a role has not been addressed so far. Case presentation We report a case of hepatitis B virus reactivation in a Caucasian patient infected with hepatitis C virus during treatment with sofosbuvir and velpatasvir. A 50-year-old man with a genotype 1a hepatitis C virus infection was considered for therapy. His serological profile was hepatitis B virus surface antigen-negative, hepatitis B virus core antibody-positive, hepatitis B virus surface antibody-negative, and anti-hepatitis D virus-positive. The detection of hepatitis B virus deoxyribonucleic acid (DNA) indicated active viral replication during the direct acting antiviral treatment that spontaneously returned to undetectable levels after treatment completion. Starting from week 12 after the end of treatment, hepatitis B virus surface antibody titers and hepatitis B virus e antibody developed. Sequencing analysis revealed the hepatitis B virus genotype D3 and the presence of two relevant immune-escape mutations (P120S and T126I) in the major hydrophilic region by analyzing the S region. Conclusions We speculate that the presence of the hepatitis B virus surface antigen mutations, endowed with the enhanced capability to elude the immune response, could play a role in hepatitis B virus reactivation. This observation confirms that occult hepatitis B infection should also be carefully monitored, through surveillance of the hepatitis B virus viral load before and during direct acting antiviral treatment of hepatitis C virus.

Published
2019

14. Resistance test guided retreatment of HCV infected patients with a previous failure to a NS5A inhibitor-containing regimen: the Italian Vironet C real life experience

Author

Pietro Lampertico, Valeria Cento, Claudio Maria Mastroianni, M. Puoti, Giuliano Rizzardini, Maurizio Zazzi, M. Lichtner, Bianca Bruzzone, Ivana Maida, Elisabetta Degasperi, C.F. Perno, M. Rendina, Giustino Parruti, Vincenza Calvaruso, Gloria Taliani, F. Di Lorenzo, Ilaria Lenci, Anna Claudia Pellicelli, Caterina Pasquazzi, Stefania Paolucci, A. Raddi, Marianna Aragri, Ennio Polilli, Giulia Morsica, Mario Starace, M. Andreoni, M. Di Stefano, C. Minichini, L. Donnarumma, V. Guarneri, Simona Marenco, Simona Landonio, Raffaele Cozzolongo, V. Pace Palitti, N. Cuomo, P. Andreone, Nicola Coppola, Silvia Galli, Mario Angelico, C. Paternoster, Roberto Ganga, Vanni Borghi, Elisabetta Teti, Sergio Babudieri, Silvia Barbaliscia, Anna Licata, Giovanni Cenderello, Antonio Craxì, Filomena Morisco, Maurizia Rossana Brunetto, V.C. Di Maio, Vincenzo Sangiovanni, A. Ciancio, Piero Colombatto, Valeria Micheli, Teresa Pollicino, Laura Ambra Nicolini, Alessia Giorgini, Valeria Ghisetti, S. Novati, Annapaola Callegaro, Aldo Bertoli, E. Milano, Roberto Gulminetti, A. De Santis, F. Ceccherini-Silberstein, Teresa Santantonio, C. Masetti, G. Raimondo, Di Maio, V.C., Aragri, M., Masetti, C., Paolucci, S., Bruzzone, B., Degasperi, E., Barbaliscia, S., Pollicino, T., Minichini, C., Calvaruso, V., Rendina, M., Cento, V., Teti, E., Micheli, V., Ghisetti, V., Polilli, E., Palitti, V. Pace, Landonio, S., Lenci, I., Donnarumma, L., Nicolini, L.A., Bertoli, A., Starace, M., Pasquazzi, C., Callegaro, A.P., Morisco, F., Cenderello, G., Marenco, S., Gulminetti, R., Novati, S., Guarneri, V., Andreone, P., Galli, S., Ciancio, A., Sangiovanni, V., Cuomo, N., Raddi, A., Morsica, G., Borghi, V., Maida, I., Brunetto, M., Colombatto, P., Cozzolongo, R., De Santis, A., Lichtner, M., Babudieri, S., Taliani, G., Santantonio, T., Di Stefano, M., Paternoster, C., Ganga, R., Puoti, M., Rizzardini, G., Pellicelli, A., Milano, E., Mastroianni, C., Licata, A., Di Lorenzo, F., Giorgini, A., Lampertico, P., Parruti, G., Coppola, N., Zazzi, M., Raimondo, G., Andreoni, M., Craxì, A., Angelico, M., Perno, C.F., and Ceccherini-Silberstein, F.

Subjects
Resistance test, medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, DAA failur, Vironet C, NS5A, Regimen, Internal medicine, medicine, retreatment, business
Abstract

Previous article in issueNext article in issue Introduction: There is a limited documentation about the retreatment of patients failing a recommended NS5A-containing regimen in Italy. Materials & methods: Within the VIRONET-C network, 386 NS5A-failing patients infected with different HCV-genotypes (GT) (GT1a/1b/2a-c/3a-b-g-h/4a-d-n-o-v=93/124/19/112/38) were analyzed. Retreatment of 105 failures was investigated. HCV-resistance-test was performed by Sanger-sequencing. Results: Failures following seven different NS5A-containing regimens were studied: 3D/2D (paritaprevir/ombitasvir ± dasabuvir) ± ribavirin (N = 72/4), daclatasvir/ledipasvir/velpatasvir + sofosbuvir ± ribavirin (N = 105/131/20), grazoprevir/elbasvir ± ribavirin (N = 34), glecaprevir/pibrentasvir (N = 20). Notably, 18.1% of NS5A-failing patients did not show any resistance-associated-substitutions (RAS), while 81.9% showed at least one NS5A-RAS, with multiclass-resistance in 35.5%. NS5A-RAS were observed more frequently in glecaprevir/pibrentasvir failures (GT1a 83.3%: Y93H + Q30H/D or +H58D; GT3a: 83.3% Y93H + A30K/G or +L31I) compared to sofosbuvir/velpatasvir (GT1a 16.6%: Y93H + Q30H, p = 0.08; GT3a 20.0%: Y93H/N + A30K/T, p = 0.03). To date, 105 failures have started a retreatment: sofosbuvir/velpatasvir ± ribavirin (N = 30), sofosbuvir/velpatasvir/voxilaprevir ± ribavirin (N = 67), glecaprevir/pibrentasvir (N = 4), grazoprevir/elbasvir ± sofosbuvir + ribavirin (N = 3), 3D + sofosbuvir + ribavirin (N = 1). The majority of patients were cirrhotic (51.9%) and relapsers (87.5%). The prevalence of NS5A-RASs before retreatment was 80.9%, with multiclass-resistance 29.5%. Among patients completing post-retreatment follow-up, a sustained-viral-response at week 12 (SVR12) was observed in 26/33 (78.8%). SVR4 was documented in 49/56 (87.5%). SVR12 was 76.0% with sofosbuvir/velpatasvir ± ribavirin (N = 25). Differently, SVR12 was 100% with glecaprevir/pibrentasvir for 8/12/16 weeks (N = 3), grazoprevir/elbasvir ± sofosbuvir + ribavirin for 12/24 weeks (N = 3) or 3D + sofosbuvir + ribavirin for 24 weeks (N = 1), despite the presence of NS5A-RASs. Until now, 67 patients started sofosbuvir/velpatasvir/voxilaprevir ± ribavirin recommended-retreatment for 12 weeks. 54/67 (80.6%) showed at least one baseline NS5A-RAS, 23/67 (34.3%) multiple-NS5A-RASs, and 22/67 (32.8%) multiclass-resistance. Of 25 patients with available outcome, 96.0% had SVR4. Only 1 GT1b infected patient was non-responder, without RASs before retreatment. Conclusions: In this real-life setting, NS5A-RASs were frequently detected at failure, and multiclass-resistance was around 30%. Overall, SVR after resistance-test-guided retreatment was >95%, with the exception of the sofosbuvir/velpatasvir retreatment. Our results show how HCV resistance-test at failure may be useful to optimize retreatment strategies.

Published
2019
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15. Consequences of inaccurate hepatitis C virus genotyping on the costs of prescription of direct antiviral agents in an Italian district

Author

Francesca Ceccherini-Silberstein, Carlo Federico Perno, Ennio Polilli, Giustino Parruti, Alberto Costantini, Velia Chiara Di Maio, Marianna Aragri, Fiorenzo Santoleri, Antonina Sciacca, Umberto Restelli, Paolo Fazii, and Valeria Cento

Subjects
0301 basic medicine, medicine.medical_specialty, Hepatitis C virus, 030106 microbiology, Economics, Econometrics and Finance (miscellaneous), Population, medicine.disease_cause, HCV sequence analysis, 03 medical and health sciences, Internal medicine, Genotype, medicine, In patient, Medical prescription, education, Genotyping, Original Research, education.field_of_study, lcsh:R5-920, HCV, HCV genotype, direct acting antiviral, treatment costs, business.industry, Health Policy, Treatment costs, lcsh:RM1-950, Settore MED/07 - Microbiologia e Microbiologia Clinica, Virology, ClinicoEconomics and Outcomes Research, Regimen, lcsh:Therapeutics. Pharmacology, Direct Acting Antiviral, business, lcsh:Medicine (General), Direct acting
Abstract

Ennio Polilli,1 Valeria Cento,2 Umberto Restelli,3,4 Francesca Ceccherini-Silberstein,2 Marianna Aragri,2 Velia Chiara Di Maio,2 Antonina Sciacca,1 Fiorenzo Santoleri,5 Paolo Fazii,6 Alberto Costantini,5 Carlo Federico Perno,2 Giustino Parruti1 1Infectious Diseases Unit, Pescara General Hospital, Pescara, 2Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Rome, 3CREMS - Centre for Research on Health Economics, Social and Health Care Management, Carlo Cattaneo – LIUC University, Castellanza, Italy; 4School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 5Hospital Pharmacy, Pescara General Hospital, 6Microbiology and Virology Unit, Pescara General Hospital, Pescara, Italy Abstract: Available commercial assays may yield inaccurate hepatitis C virus (HCV) genotype assignment in up to 10% of cases. We investigated the cost-effectiveness of re-evaluating HCV genotype by population sequencing, prior to choosing a direct acting antiviral (DAA) regimen. Between March and September 2015, HCV sequence analysis was performed in order to confirm commercial LiPA-HCV genotype (Versant® HCV Genotype 2.0) in patients eligible for treatment with DAAs. Out of 134 consecutive patients enrolled, sequencing yielded 21 (15.7%) cases of discordant results. For three cases of wrong genotype assignment, the putative reduction in efficacy was gauged between 15% and 40%. Among the eight cases for whom G1b was assigned by commercial assays instead of G1a, potentially suboptimal treatments would have been prescribed. Finally, for five patients with G1 and indeterminate subtype, the choice of regimens would have targeted the worst option, with a remarkable increase in costs, as in the case of the four mixed HCV infections for whom pan-genotypic regimens would have been mandatory. Precise assignment of HCV genotype and subtype by sequencing may, therefore, be more beneficial than expected, until more potent pan-genotypic regimens are available for all patients. Keywords: HCV, HCV sequence analysis, HCV genotype, direct acting antiviral, treatment costs

Published
2016

16. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels

Author

Di Maio, V C, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M C, Antonucci, F P, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L A, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C F, Babudieri, S, Mura, M S, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C F, Ceccherini-Silberstein, F, Collaborators (129) Mariani R, HCV Italian Resistance Network Study Group., Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Nicolini, La, Viscoli, C, Casinelli, K, Monache, Md, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, Monforte, Ad, Danieli, E, Donato, F, Gubertini, G, Magni, Cf, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, Ml, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, Gb, Lembo, V, Calvaruso, V, Craxì, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Palitti, Vp, Pieri, A, Polilli, E, Antenucci, F, Antonucci, Fp, Armenia, D, Baiocchi, L, Bellocchi, M, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Di Maio VC, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Perno, Cf, Santopaolo, F, Santoro, Mm, Sforza, D, Sorbo, Mc, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Mura, Ms, Falconi, L, Di Giammartino, D, Tarquini, P., Di Maio, V C, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M C, Antonucci, F P, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L A, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C F, Babudieri, S, Mura, M S, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C F, Ceccherini-Silberstein, F, HCV Italian Resistance Network Study Group., Collaborators (129) Mariani R, Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Nicolini, La, Viscoli, C, Casinelli, K, Monache, Md, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, Monforte, Ad, Danieli, E, Donato, F, Gubertini, G, Magni, Cf, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, Ml, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, Gb, Lembo, V, Calvaruso, V, Craxì, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Palitti, Vp, Pieri, A, Polilli, E, Antenucci, F, Antonucci, Fp, Armenia, D, Baiocchi, L, Bellocchi, M, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Di Maio, Vc, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Perno, Cf, Santopaolo, F, Santoro, Mm, Sforza, D, Sorbo, Mc, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Mura, M, Falconi, L, Di Giammartino, D, Tarquini, P., Di Maio, V. C, Bellocchi, M. C, Antonucci, F. P, Nicolini, L. A, Magni, C. F, Mura, M. S, Vespasiani Gentilucci, U, Morisco, Filomena, Perno, C. F, Ceccherini Silberstein, F., Caporaso, Nicola, Di Maio, V., Cento, V., Di Paolo, D., Aragri, M., De Leonardis, F., Tontodonati, M., Micheli, V., Bellocchi, M., Antonucci, F., Bertoli, A., Lenci, I., Milana, M., Gianserra, L., Melis, M., Di Biagio, A., Sarrecchia, C., Sarmati, L., Landonio, S., Francioso, S., Lambiase, L., Nicolini, L., Marenco, S., Nosotti, L., Giannelli, V., Siciliano, M., Romagnoli, D., Pellicelli, A., Vecchiet, J., Magni, C., Babudieri, S., Mura, M., Taliani, G., Mastroianni, C., Vespasiani-Gentilucci, U., Romano, M., Morisco, F., Gasbarrini, A., Vullo, V., Bruno, S., Baiguera, C., Pasquazzi, C., Tisone, G., Picciotto, A., Andreoni, M., Parruti, G., Rizzardini, G., Angelico, M., Perno, C., Ceccherini-Silberstein, F., Mariani, R., Paoloni, M., Iapadre, N., Grimaldi, A., Menzaghi, B., Quirino, T., Bruzzone, B., De Maria, A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, M., Aghemo, A., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Mancon, A., Monico, S., Niero, F., Puoti, M., Russo, M., Alfieri, R., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Caporaso, N., Gaeta, G., Lembo, V., Calvaruso, V., Craxã­, A., DI MARCO, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pace Palitti, V., Pieri, A., Polilli, E., Antenucci, F., Armenia, D., Baiocchi, L., Biliotti, E., Biolato, M., Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Sanctis, A., Furlan, C., Gallo, P., Grieco, A., Grieco, S., Lattanzi, B., Malagnino, V., Manuelli, M., Merli, M., Miglioresi, L., Palazzo, D., Santopaolo, F., Santoro, M., Sforza, D., Sorbo, M., Spaziante, M., Svicher, V., Teti, E., Mangia, A., Maida, I., Falconi, L., and Di Giammartino, D.

Subjects
0301 basic medicine, ns3, Genotyping Techniques, viruses, Drug Resistance, Hepacivirus, Viral Nonstructural Proteins, medicine.disease_cause, Gastroenterology, Telaprevir, chemistry.chemical_compound, genotype, genotyping techniques, hepacivirus, hepatitis C, humans, RNA viral, retrospective studies, sequence analysis, DNA, viral nonstructural proteins, drug resistance, viral, mutation, pharmacology, infectious diseases, 0302 clinical medicine, Retrospective Studie, Genotype, Pharmacology (medical), Viral, Hepatitis C, Humans, RNA, Viral, Retrospective Studies, Sequence Analysis, DNA, Drug Resistance, Viral, Mutation, Proteolytic enzymes, virus diseases, Settore MED/07 - Microbiologia e Microbiologia Clinica, hcv-rna levels, Infectious Diseases, HCV-RNA, 030211 gastroenterology & hepatology, Sequence Analysis, medicine.drug, Human, Microbiology (medical), medicine.medical_specialty, Hepatitis C virus, Concordance, Settore MED/12 - GASTROENTEROLOGIA, Pharmacology, Biology, 03 medical and health sciences, Boceprevir, Internal medicine, medicine, hcv, Genotyping, Hepaciviru, Viral Nonstructural Protein, Settore MED/09 - MEDICINA INTERNA, Virology, digestive system diseases, 030104 developmental biology, chemistry, Sequence Analysi, RNA, Genotyping Technique
Abstract

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Published
2016
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17. Multiple Hepatitis B Virus (HBV) Quasispecies and Immune-Escape Mutations Are Present in HBV Surface Antigen and Reverse Transcriptase of Patients with Acute Hepatitis B

Author

Carlo Federico Perno, Michela Pollicita, Maria Concetta Bellocchi, Marianna Aragri, A. Battisti, Mario Starace, Evangelista Sagnelli, Maria Antonietta Pisaturo, Domenico Di Carlo, Nicola Coppola, Daniele Armenia, Carmine Minichini, Valentina Svicher, L. Carioti, Romina Salpini, Caterina Sagnelli, Claudia Alteri, Aragri, M, Alteri, C, Battisti, A, Di Carlo, D, Minichini, C, Sagnelli, Caterina, Bellocchi, Mc, Pisaturo, Ma, Starace, M, Armenia, D, Carioti, L, Pollicita, M, Salpini, R, Sagnelli, Evangelista, Perno, Cf, Coppola, Nicola, Svicher, V., Aragri, M., Alteri, C., Battisti, A., Di Carlo, D., Minichini, C., Sagnelli, C., Bellocchi, M. C., Pisaturo, M. A., Starace, M., Armenia, D., Carioti, L., Pollicita, M., Salpini, R., Sagnelli, E., Perno, C. F., and Coppola, N.

Subjects
Male, 0301 basic medicine, HBsAg, Hepatitis B Surface Antigen, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Genotype, Prevalence, HBV, Immunology and Allergy, High-Throughput Nucleotide Sequencing, virus diseases, RNA-Directed DNA Polymerase, Hepatitis B viru, Middle Aged, Hepatitis B, Settore MED/07 - Microbiologia e Microbiologia Clinica, Infectious Diseases, Italy, Acute Disease, Female, 030211 gastroenterology & hepatology, Human, Adult, Hepatitis B virus, Viral quasispecies, Hepatitis B virus PRE beta, 03 medical and health sciences, Antigen, Drug Resistance, Viral, reverse transcriptase, medicine, Humans, acute infection, quasispecies, Quasispecie, Hepatitis B Surface Antigens, business.industry, Genetic Variation, Sequence Analysis, DNA, medicine.disease, Virology, digestive system diseases, Reverse transcriptase, 030104 developmental biology, Amino Acid Substitution, Mutation, Immunology, Cohort Studie, business
Abstract

Background. This study characterizes and defines the clinical value of hepatitis B virus (HBV) quasispecies with reverse transcriptase and HBV surface antigen (HBsAg) heterogeneity in patients with acute HBV infection. Methods. Sixty-two patients with acute HBV infection (44 with genotype D infection and 18 with genotype A infection) were enrolled from 2000 to 2010. Plasma samples obtained at the time of the first examination were analyzed by ultradeep pyrosequencing. The extent of HBsAg amino acid variability was measured by Shannon entropy. Results. Median alanine aminotransferase and serum HBV DNA levels were 2544 U/L (interquartile range, 1938-3078 U/L) and 5.88 log10 IU/mL (interquartile range, 4.47-7.37 log10 IU/mL), respectively. Although most patients serologically resolved acute HBV infection, only 54.1% developed antibody to HBsAg (anti-HBs). A viral population with ≥1 immune-escape mutation was found in 53.2% of patients (intrapatient prevalence range, 0.16%-100%). Notably, by Shannon entropy, higher genetic variability at HBsAg amino acid positions 130, 133, and 157 significantly correlated with no production of anti-HBs in individuals infected with genotype D (P

Published
2016

18. Reactivation of Hepatitis B Virus With Immune-Escape Mutations After Ocrelizumab Treatment for Multiple Sclerosis

Author

Valentina Svicher, Romina Salpini, Maria Rosa Ciardi, Gianluca Russo, Vincenzo Vullo, Simona Pontecorvo, Marta Altieri, Rosanna Annecca, Maria Antonella Zingaropoli, Claudio Maria Mastroianni, Marco Iannetta, and Marianna Aragri

Subjects
0301 basic medicine, 030106 microbiology, medicine.disease_cause, liver, 03 medical and health sciences, 0302 clinical medicine, Antigen, HBV, Medicine, CD20, biologics, entecavir, prophylaxis, 030212 general & internal medicine, ID Cases, Hepatitis B virus, biology, business.industry, Multiple sclerosis, virus diseases, Entecavir, medicine.disease, Settore MED/07 - Microbiologia e Microbiologia Clinica, Virology, digestive system diseases, Settore MED/17, Infectious Diseases, Oncology, Viral replication, biology.protein, Rituximab, Ocrelizumab, business, medicine.drug
Abstract

Ocrelizumab is an anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS) that is closely related to rituximab. We describe a case of hepatitis B virus (HBV) reactivation in an MS patient with resolved HBV infection receiving ocrelizumab. HBV reactivation was monitored with HBV-DNA and HBV surface antigen periodic assessment. Anti-HBV treatment with entecavir was started after HBV-DNA detection. Ocrelizumab can reactivate viral replication in patients with resolved HBV infection. HBV reactivation monitoring seems an effective and safe option for the management of these patients. More studies are needed to assess the optimal management of HBV reactivation in MS patients on ocrelizumab treatment.

Published
2019

19. THU-117-Evaluation of risk factors associated with failure to a first-line NS5A-containing regimen in HCV-infected patients naive to direct acting antivirals: Particular focus on natural resistance

Author

Pietro Lampertico, Giulia Morsica, Silvia Galli, Giustino Parruti, Pietro Andreone, Adriano M. Pellicelli, Velia Chiara Di Maio, Rossana Scutari, Carlo Federico Perno, Antonio Craxì, Ada Bertoli, Filomena Morisco, Caterina Pasquazzi, Stefano Bonora, Vincenza Calvaruso, Roberta D'Ambrosio, Laura Ambra Nicolini, Riccardo Campoli, Francesca Ceccherini Silberstein, Valeria Ghisetti, Elisabetta Teti, V. Boccaccio, Gloria Taliani, Miriam Lichtner, Silvia Barbaliscia, Valeria Micheli, Luca Foroghi, Carlo Magni, Massimo Siciliano, Massimo Andreoni, Giovanni Battista Gaeta, P Paba, Ennio Polilli, Giuliano Rizzardini, Martina Milana, Bianca Bruzzone, Valeria Pace Palitti, Stefania Paolucci, Massimo Puoti, Angelico Mario, Vanni Borghi, C. Masetti, Renato Maserati, Coppola Nicola, Sergio Babudieri, Valeria Cento, N. Iapadre, Loredana Sarmati, Marianna Aragri, and Gianluca Fiorentino

Subjects
Oncology, medicine.medical_specialty, Focus (computing), Hepatology, business.industry, First line, HCV, NS5A, risk factors, DIRECT ACTING ANTIVIRALS, NS5A, Natural resistance, Regimen, Internal medicine, HCV, medicine, risk factors, business
Published
2019

20. Key mutations in HBsAg C-terminus correlate with lower HBsAg levels in vivo, hinder HBsAg release in vitro and affect HBsAg structural stability in HBeAg-negative chronic HBV genotype D infection

Author

Angelico Mario, U.S. Gill, Luna Colagrossi, L. Sarmati, Claudio Maria Mastroianni, Marianna Aragri, F. Ceccherini Silberstein, Massimo Marignani, Carlotta Cerva, J. Vecchiet, N. Iapadre, Giustino Parruti, Vincenzo Malagnino, T. Mari, M. Lichtner, R. Salpini, A. Battisti, Olympia E. Anastasiou, M. Andreoni, G. De Sanctis, L. Piermatteo, Sandro Grelli, A. Iuvara, Aldo Bertoli, L. Carioti, V. Svicher, Jens Verheyen, Caterina Pasquazzi, Patrick T F Kennedy, P. Maurizio, and C.F. Perno

Subjects
HBsAg, Hepatology, business.industry, C-terminus, Gastroenterology, Medizin, Affect (psychology), Virology, In vitro, Hbeag negative, In vivo, Hbv genotype, Medicine, business
Published
2019

21. Analysis of resistance and phylogenetic clusters in HCV-2c infected patients within the Italian network Vironet C

Author

Anna Claudia Pellicelli, Alessandro Pieri, Enzo Boeri, V. Pace Palitti, Roberto Gulminetti, V. Di Marco, Stefania Paolucci, Simona Landonio, F. Di Lorenzo, Laura Monno, L. Sarmati, Stefano Novati, Annapaola Callegaro, Simona Marenco, G. Raimondo, Lavinia Fabeni, Maurizio Zazzi, Silvia Barbaliscia, Nicola Coppola, P. Andreone, L. Carioti, Claudio Maria Mastroianni, Anna Licata, Fausto Baldanti, M. Andreoni, M. Quartini, M. Lichtner, Gloria Taliani, Laura Ambra Nicolini, Francesca Ceccherini-Silberstein, C.F. Perno, Luca Foroghi, Giustino Parruti, Bianca Bruzzone, Caterina Pasquazzi, C. Paternoster, Martina Milana, Sergio Babudieri, K. Yu La Rosa, M. Puoti, Hamid Hasson, Teresa Pollicino, N. Iapadre, C. Minichini, Raffaele Cozzolongo, Valeria Micheli, Barbara Rossetti, Aldo Bertoli, Elisabetta Teti, Marianna Aragri, Antonio Craxì, Filomena Morisco, V.C. Di Maio, Vincenzo Sangiovanni, Leonardo Baiocchi, and Mario Angelico

Subjects
Genetics, Hepatology, Resistance (ecology), Phylogenetic tree, business.industry, Gastroenterology, Medicine, business
Published
2020
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22. VIRONET-C real life experience of resistance-guided retreatment in HCV infected patients who previously failed a NS5A inhibitor-containing regimen

Author

Mario Starace, Valerio Giannelli, Nunzia Cuomo, Vanni Borghi, Aldo Bertoli, Anna Licata, Anna Claudia Pellicelli, C. Minichini, M. Andreoni, M. Di Stefano, Giuseppe Cariti, Enzo Boeri, Raffaele Cozzolongo, Roberto Gulminetti, E. Milano, Valeria Cento, Elisabetta Degasperi, Laura Sighinolfi, A. Raddi, Ivana Maida, Barbara Rossetti, Teresa Santantonio, Valeria Micheli, C. Masetti, P. Andreone, Giustino Parruti, F. Di Lorenzo, Ilaria Lenci, Tiziano Allice, Annapaola Callegaro, Elisa Biliotti, M. Lichtner, Teresa Pollicino, Pietro Lampertico, Gloria Taliani, Caterina Pasquazzi, Piero Colombatto, Alessia Giorgini, G. Raimondo, Antonio Craxì, Francesca Ceccherini-Silberstein, Filomena Morisco, Valeria Ghisetti, V.C. Di Maio, Giuliano Rizzardini, Silvia Galli, Stefania Paolucci, A. De Santis, A. Lleo, Vincenzo Sangiovanni, A. Ciancio, Maurizio Zazzi, Elisabetta Teti, Simona Marenco, William Gennari, Stefano Novati, Giovanni Cenderello, Simona Landonio, Manuela Merli, A. Scuteri, Nicola Coppola, C.F. Perno, Giulia Morsica, I. Beretta, Claudio Maria Mastroianni, Simona Francioso, Mario Angelico, Laura Ambra Nicolini, Chiara Dentone, Silvia Barbaliscia, G.B. Gaeta, Marianna Aragri, Ennio Polilli, L. Donnarumma, Vincenza Calvaruso, Bianca Bruzzone, Fausto Baldanti, V. Pace Palitti, Roberto Ganga, Maurizia Rossana Brunetto, C. Paternoster, Sergio Babudieri, M. Puoti, Hamid Hasson, and M. Rendina

Subjects
medicine.medical_specialty, Regimen, Hepatology, business.industry, Internal medicine, Gastroenterology, medicine, business, NS5A
Published
2020
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23. THU-133-Resistance-guided retreatment of HCV infected patients with a previous failure to an NS5A inhibitor-containing regimen: Italian real life experience

Author

Ada Bertoli, Gloria Taliani, Ilaria Lenci, Stefano Novati, Teresa Santantonio, Raffaele Cozzolongo, C. Masetti, Nunzia Cuomo, Laura Donnarumma, Giovanni Cenderrello, Silvia Barbaliscia, Adriano De Santis, Bianca Bruzzone, Giovanni Raimondo, Massimo Puoti, Carlo Federico Perno, Simona Landonio, Roberto Gulminetti, Elisabetta Degasperi, Giustino Parruti, Vincenza Calvaruso, Marianna Aragri, Teresa Pollicino, Pietro Lampertico, Laura Ambra Nicolini, Velia Chiara Di Maio, Valeria Ghisetti, Adriano M. Pellicelli, Ivana Maida, Caterina Pasquazzi, Valeria Cento, Roberto Ganga, Coppola Nicola, C. Paternoster, Maurizia Rossana Brunetto, Alessia Ciancio, Sergio Babudieri, Massimo Andreoni, Silberstein Francesca Ceccherini, Maurizio Zazzi, Maria Rendina, Miriam Lichtner, Angelico Mario, Ennio Polilli, Giuliano Rizzardini, Vanni Borghi, Maria Paola Callegaro, Valeria Pace Palitti, Stefania Paolucci, Carmine Minichini, Simona Marenco, Antonio Craxì, Filomena Morisco, Vincenzo Sangiovanni, Giulia Morsica, Valeria Micheli, Elisabetta Teti, and Pietro Andreone

Subjects
medicine.medical_specialty, Regimen, Hepatology, business.industry, Internal medicine, medicine, NS5A, business
Published
2019
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24. SAT-159-Genetic determinants in critical domains of NS5A are associated with genotype 1b HCV-induced hepatocellular carcinoma

Author

Rossana Scutari, Valeria Cento, C. Masetti, Elisabetta Teti, Francesca Ceccherini Silberstein, Cristina Mussini, Massimo Andreoni, Ada Bertoli, Simona Francioso, Caterina Pasquazzi, Marianna Aragri, Silvia Barbaliscia, Carlo Federico Perno, Vincenza Calvaruso, Ivana Maida, Giustino Parruti, Valentina De Murtas, Angelica Sacco, Velia Chiara Di Maio, Mohammad Alkhatib, Ilaria Lenci, Federica Sozio, Angelico Mario, Alessandro Pieri, Maria Mercedes Santoro, Vanni Borghi, Antonio Craxì, Filomena Morisco, Valeria Pace Palitti, Romina Salpini, Valentina Svicher, Sergio Babudieri, Ennio Polilli, and P. Cacciatore

Subjects
Hepatology, Genotype 1b, Hepatocellular carcinoma, medicine, Cancer research, Biology, NS5A, medicine.disease
Published
2019
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25. Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life

Author

L. Lambiase, Anna Claudia Pellicelli, Gloria Taliani, Barbara Menzaghi, Stefania Paolucci, Giuliano Rizzardini, Valeria Cento, Cesare Sarrecchia, Marianna Aragri, Francesca Ceccherini-Silberstein, M. Melis, M. Andreoni, Stefano Novati, Carlo Magni, Silvia Barbaliscia, Ilaria Lenci, V.C. Di Maio, Martina Milana, Elisabetta Teti, Mario Angelico, Caterina Pasquazzi, Aldo Bertoli, M. Puoti, A. Pecchioli, Valeria Micheli, Margherita Macera, Sergio Babudieri, Dante Romagnoli, Valeria Ghisetti, Laura Ambra Nicolini, Elisa Biliotti, Y. Troshina, Carlo Federico Perno, Fausto Baldanti, Simona Marenco, Nicola Coppola, T. Ruggiero, Manuele Koci Siciliano, Stefano Bonora, Alessia Ciancio, Cento, V, Barbaliscia, S, Lenci, I, Ruggiero, T, Magni, C, Paolucci, S, Babudieri, S, Siciliano, M, Pasquazzi, C, Ciancio, A, Perno, C, Ceccherini-Silberstein, F, Micheli, V, Troshina, Y, Biliotti, E, Milana, M, Melis, M, Teti, E, Lambiase, L, Menzaghi, B, Nicolini, L, Marenco, S, Di Maio, V, Aragri, M, Pecchioli, A, Bertoli, A, Sarrecchia, C, Macera, M, Coppola, N, Puoti, M, Romagnoli, D, Pellicelli, A, Bonora, S, Novati, S, Baldanti, F, Ghisetti, V, Andreoni, M, Taliani, G, Rizzardini, G, Angelico, M, Barbaliscia, I, and Ceccherini Silberstein, F

Subjects
0301 basic medicine, Male, Cirrhosis, Genotyping Techniques, Sustained Virologic Response, Hepacivirus, Treatment failure, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, NS5A-inhibitors, Genotypic resistance testing, Treatment Failure, Chronic, HCV resistance, biology, Direct acting antivirals, HCV failure, Protease-inhibitors, Retreatment, Adult, Aged, Antiviral Agents, Female, Hepatitis C, Chronic, Humans, Microbial Sensitivity Tests, Middle Aged, Protease Inhibitors, Sequence Analysis, DNA, General Medicine, Settore MED/07 - Microbiologia e Microbiologia Clinica, Protease-inhibitor, Hepatitis C, humanities, Infectious Diseases, DIrect acting antivirals, HCVFailure, hcv-resistance, 030211 gastroenterology & hepatology, Sequence Analysis, Microbiology (medical), medicine.medical_specialty, 03 medical and health sciences, Internal medicine, medicine, In real life, Protease inhibitor (pharmacology), Cirrhosi, business.industry, Ribavirin, DNA, biology.organism_classification, medicine.disease, Surgery, Regimen, 030104 developmental biology, chemistry, NS5A-inhibitor, Direct acting antiviral, business
Abstract

Objectives First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. Methods In this multi-centre observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. Results After PI-failure, 121 patients (cirrhotic = 86.8%) were retreated following three different strategies: A) with ‘GRT-guided’ regimens (N = 18); B) with ‘AASLD/EASL recommended, not GRT-guided’ regimens (N = 72); C) with ‘not recommended, not GRT-guided’ regimens (N = 31). Overall SVR rate was 91%, but all 18 patients treated with ‘GRT-guided’ regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving ‘AASLD/EASL recommended, not GRT-guided’ regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a ‘not recommended, not GRT-guided regimen’ (p

Published
2017

26. NS5A gene analysis by next generation sequencing in HCV nosocomial transmission clusters of HCV genotype 1b infected patients

Author

Stefania Grimaudo, Lavinia Fabeni, Giuseppina Brancaccio, Carlo Federico Perno, Marco Cantone, L. Carioti, Antonio Pinto, M.C. Sorbo, Giovanni Battista Gaeta, Maria Concetta Bellocchi, Francesca Ceccherini-Silberstein, Velia Chiara Di Maio, Antonio Craxì, Vito Di Marco, Marianna Aragri, Ferdinando Frigeri, Fabrizio Bronte, Silvia Barbaliscia, Walter Mazzucco, Rosaria Maria Pipitone, Bellocchi, Maria Concetta, Aragri, Marianna, Carioti, Luca, Fabeni, Lavinia, Pipitone, Rosaria Maria, Brancaccio, Giuseppina, Sorbo, Maria Chiara, Barbaliscia, Silvia, Di Maio, Velia Chiara, Bronte, Fabrizio, Grimaudo, Stefania, Mazzucco, Walter, Frigeri, Ferdinando, Cantone, Marco, Pinto, Antonio, Perno, Carlo Federico, Craxì, Antonio, Gaeta, Giovanni Battista, Di Marco, Vito, and Ceccherini-Silberstein, Francesca

Subjects
Male, 0301 basic medicine, viruses, Drug Resistance, Hepacivirus, Viral Nonstructural Proteins, medicine.disease_cause, Settore MED/42 - Igiene Generale E Applicata, Gastroenterology, Settore MED/07, chemistry.chemical_compound, 0302 clinical medicine, Genotype 1b, Medicine, Viral, lcsh:QH301-705.5, Phylogeny, Cross Infection, nosocomial transmission, High-Throughput Nucleotide Sequencing, virus diseases, HCV, NGS, acute infection, chronic infection, sequencing, Acute Disease, Adult, Amino Acid Substitution, Antiviral Agents, Blood Transfusion, Chronic Disease, Drug Resistance, Viral, Female, Genotype, Hepatitis C, Host-Pathogen Interactions, Humans, Interferons, Middle Aged, Polymorphism, Single Nucleotide, beta-Thalassemia, Single Nucleotide, General Medicine, 030211 gastroenterology & hepatology, medicine.medical_specialty, Hepatitis C virus, Viral quasispecies, Article, DNA sequencing, 03 medical and health sciences, Internal medicine, Polymorphism, NS5A, NS5B, Gene, Hepatology, business.industry, Nosocomial transmission, biochemical phenomena, metabolism, and nutrition, Virology, digestive system diseases, Chronic infection, 030104 developmental biology, chemistry, lcsh:Biology (General), business
Abstract

Background: The aim of the study was to investigate the intra-host variability through next-generation-sequencing (NGS) of the NS5A-gene in nosocomial transmission-clusters observed in two Italian hospitals among hepatitis C virus (HCV)-genotype-1b infected patients. Methods: HCV-sequencing was performed by Sanger-sequencing (NS3 + NS5A + NS5B) and by NGS (NS5A, MiSeq-Illumina) in 15 HCV-1b infected patients [five acute with onco-hematologic-disease and 10 (4/6 acute/chronic) with &beta, thalassemia]. Resistance-associated-substitutions (RAS) were analysed by Geno2pheno-algorithm. Nucleotide-sequence-variability (NSV, at 1%, 2%, 5%, 10% and 15% NGS-cutoffs) and Shannon entropy were estimated. Phylogenetic analysis was performed by Mega6-software and Bayesian-analysis. Results: Phylogenetic analysis showed five transmission-clusters: one involving four HCV-acute onco-hematologic-patients, one involving three HCV-chronic &beta, thalassemia-patients and three involving both HCV-acute and chronic &beta, thalassemia-patients. The NS5A-RAS Y93H was found in seven patients, distributed differently among chronic/acute patients involved in the same transmission-clusters, independently from the host-genetic IL-28-polymorphism. The intra-host NSV was higher in chronic-patients versus acute-patients, at all cutoffs analyzed (p &lt, 0.05). Even though Shannon-entropy was higher in chronic-patients, significantly higher values were observed only in chronic &beta, thalassemia-patients versus acute &beta, thalassemia-patients (p = 0.01). Conclusions: In nosocomial HCV transmission-clusters, the intra-host HCV quasispecies divergence in patients with acute-infection was very low in comparison to that in chronic-infection. The NS5A-RAS Y93H was often transmitted and distributed differently within the same transmission-clusters, independently from the IL-28-polymorphism.

Published
2019
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27. A hyper-glycosylation of HBV surface antigen characterizes immunosuppression-driven HBV reactivation and hinders HBsAg recognition in vitro

Author

Angelico Mario, L. Sarmati, L. Piermatteo, Sarah Maylin, C.F. Perno, A. Battisti, M. Andreoni, Laura Belloni, Constance Delaugerre, N. Iapadre, Claudio Maria Mastroianni, Massimo Levrero, Massimo Marignani, Marianna Aragri, Luna Colagrossi, Francesca Ceccherini Silberstein, Jens Verheyen, R. Salpini, Aldo Marrone, Filomena Morisco, Aldo Bertoli, V. Svicher, Lavinia Fabeni, and Coppola Nicola

Subjects
chemistry.chemical_compound, HBsAg, Glycosylation, Hepatology, chemistry, Antigen, medicine.medical_treatment, Hbv reactivation, medicine, Medizin, Immunosuppression, Virology, In vitro
Published
2018

28. Characterization of baseline factors associated with treatment outcome in HCV-infected patients naive to direct acting antivirals: particular focus on natural resistance

Author

M. Siciliano, Giulia Morsica, Anna Claudia Pellicelli, Silvia Galli, F. Ceccherini-Silberstein, Fausto Baldanti, Bianca Bruzzone, R. Campoli, Giuliano Rizzardini, Vincenza Calvaruso, Gloria Taliani, V. Pace Palitti, C. Masetti, P Paba, Antonio Craxì, Filomena Morisco, Ennio Polilli, V.C. Di Maio, Martina Milana, William Gennari, C.F. Perno, Rossana Scutari, Aldo Bertoli, Valeria Cento, M. Andreoni, V. Boccaccio, Marianna Aragri, G.B. Gaeta, M. Lichtner, Caterina Pasquazzi, Vanni Borghi, Laura Ambra Nicolini, Renato Maserati, G. Fiorentino, Sergio Babudieri, Elisabetta Degasperi, Giustino Parruti, Mario Angelico, L. Foroghi, Valeria Ghisetti, Silvia Barbaliscia, Carlo Magni, Valeria Micheli, Elisabetta Teti, Nicola Coppola, Stefania Paolucci, L. Sarmati, R. D’Ambrosio, Pietro Lampertico, M. Puoti, N. Iapadre, Stefano Bonora, and V. Guarneri

Subjects
Natural resistance, Oncology, Focus (computing), medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Treatment outcome, Gastroenterology, medicine, Baseline (configuration management), DIRECT ACTING ANTIVIRALS, business
Published
2019
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29. Comparison of resistance profiles among DAA-naive and DAA-experienced patients infected with HCV non-1 genotype in Italy

Author

Simona Francioso, A. Ciaccio, Teresa Pollicino, Bianca Bruzzone, G. Fiorentino, V. Boccaccio, Coppola Nicola, M. Puoti, Ivana Maida, Valeria Cento, Lucio Boglione, Francesca Ceccherini Silberstein, Valeria Micheli, Silvia Barbaliscia, Sergio Babudieri, Guido Gubertini, Giustino Parruti, Antonio Craxì, Vincenzo Vullo, Ennio Polilli, M. Andreoni, Filomena Morisco, Vincenzo Sangiovanni, Vincenza Calvaruso, Renato Maserati, Velia Chiara Di Maio, Maurizio Zazzi, Marianna Aragri, A. Ciancio, Barbara Rossetti, Anna Claudia Pellicelli, Elisabetta Teti, C.F. Perno, Caterina Pasquazzi, L. Sarmati, R. D’Ambrosio, Mario Angelico, Fosca Niero, Stefano Bonora, M. Rendina, Gloria Taliani, Luca Foroghi, Laura Ambra Nicolini, Aldo Bertoli, A. Lleo, G. Raimondo, T. Ruggiero, Simona Marenco, Valeria Pace Palitti, G.B. Gaeta, Stefania Paolucci, and Ilaria Lenci

Subjects
Hepatology, Resistance (ecology), business.industry, Genotype, Medicine, business, Virology
Published
2018
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30. On treatment HCV-RNA evaluation in real-life: Still a role in the era of direct acting antiviral agents?

Author

Angelico Mario, Ilaria Lenci, Valeria Micheli, L. Sarmati, Giuliano Rizzardini, C.F. Perno, M. Andreoni, Guido Gubertini, Elisabetta Teti, Simona Francioso, Francesca Ceccherini Silberstein, Valeria Cento, Monica Schiavini, Marco Ciotti, C. Masetti, Simone Passerini, Carlo Magni, Marianna Aragri, V.C. Di Maio, Aldo Bertoli, and Martina Milana

Subjects
Hepatology, business.industry, In real life, Medicine, business, Virology, Direct acting
Published
2018
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31. National quality control and validation of hepatitis C NS3, NS5A and NS5B genotypic resistance testing

Author

M.P. Callegaro, A. Lai, Enzo Boeri, G. Raimondo, E. Galmozzi, Francesca Ceccherini Silberstein, N. Cuomo, M.A.D. Stefano, Valeria Micheli, Antonio Craxì, C.F. Perno, M. Arosio, Fausto Baldanti, C. Minosse, Stefania Paolucci, Maurizio Zazzi, Maria Rosaria Capobianchi, Rosaria Santangelo, Coppola Nicola, M. L. Vatteroni, Maurizio Sanguinetti, Marianna Aragri, Valeria Cento, Giuseppina Raffa, Teresa Pollicino, Maurizia Rossana Brunetto, C. Caudai, S. Soldini, Silvia Galli, Stefano Menzo, T. Ruggiero, Valeria Ghisetti, William Gennari, D. Cavallone, Anna Rosa Garbuglia, Bianca Bruzzone, T. Santantonio, A. Raddi, Mario Starace, and Laura Monno

Subjects
NS3, Hepatology, business.industry, media_common.quotation_subject, Hepatitis C, Biology, medicine.disease, Biotechnology, chemistry.chemical_compound, chemistry, medicine, Genotypic resistance, Quality (business), business, NS5A, NS5B, media_common
Published
2018
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32. VIROLOGICAL FAILURES TO NEW DIRECT ACTING ANTIVIRALS IN A REAL LIFE SETTING MAY REQUIRE UNCONVENTIONAL REGIMENS FOR RE-TREATMENT

Author

Manuela Merli, M. Paoloni, Gabriella Verucchi, Simona Francioso, M. Melis, Vincenza Calvaruso, Caterina Pasquazzi, Marianna Aragri, F.P. Antonucci, Dante Romagnoli, Sergio Babudieri, G.B. Gaeta, M. Puoti, Ilaria Lenci, V. Pisani, Francesco Donato, Marco Biolato, Valeria Cento, D. Di Paolo, C.F. Perno, Mario Angelico, F. Ceccherini-Silberstein, Anna Claudia Pellicelli, Antonio Craxì, Filomena Morisco, V.C. Di Maio, Jacopo Vecchiet, Stefano Brillanti, Aldo Bertoli, Di Maio, VC, Cento, V, Di Paolo, D, Lenci, I, Aragri, M, Verucchi, G, Melis, M, Bertoli, A, Antonucci, FP, Francioso, S, Pellicelli, A, Calvaruso, V, Pasquazzi, C, Romagnoli, D, Biolato, M, Vecchiet, J, Morisco, F, Merli, M, Gaeta, GB, Brillanti, S, Donato, F, Puoti, M, Pisani, V, Paoloni, M, Babudieri, S, Craxi, A, Angelico, M, Perno, CF, and Ceccherini-Silberstein, F

Subjects
medicine.medical_specialty, Hepatology, business.industry, DIRECT ACTING ANTIVIRALS, Real life setting, RAS, RAVS, RAV, HCV, DAA, THERAPY, RAVS, THERAPY, RAS, RAV, HCV, DAA, 03 medical and health sciences, 0302 clinical medicine, medicine, 030211 gastroenterology & hepatology, 030212 general & internal medicine, Intensive care medicine, business
Published
2016

33. How does spatial extent of fMRI datasets affect independent component analysis decomposition?

Author

Gioacchino Tedeschi, Sossio Cirillo, Tommaso Scarabino, Erich Seifritz, Adriana Aragri, Fabrizio Esposito, Francesco Di Salle, Silvia Comani, Aragri, A., Scarabino, T., Seifritz, E., Comani, S., Cirillo, Sossio, Tedeschi, Gioacchino, Esposito, F., and DI SALLE, F.

Subjects
Adult, Multivariate statistics, Brain activity and meditation, Computer science, Image Processing, Sensitivity and Specificity, methods, exploratory data-driven analysi, Computer-Assisted, dataset spatial extent, fixed point approach, Image Processing, Computer-Assisted, medicine, Humans, Radiology, Nuclear Medicine and imaging, Research Articles, Brain Mapping, Principal Component Analysis, Radiological and Ultrasound Technology, Receiver operating characteristic, medicine.diagnostic_test, business.industry, Brain, Regression analysis, Pattern recognition, functional magnetic resonance imaging, Magnetic Resonance Imaging, Independent component analysis, Functional imaging, Acoustic Stimulation, Adult, Brain Mapping, Brain, physiology, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Photic Stimulation, Principal Component Analysis, methods, ROC Curve, Sensitivity and Specificity, Acoustic Stimulation, ROC Curve, Neurology, physiology, Female, Neurology (clinical), Artificial intelligence, Anatomy, business, Functional magnetic resonance imaging, information maximization, Photic Stimulation, Data reduction
Abstract

Spatial independent component analysis (sICA) of functional magnetic resonance imaging (fMRI) time series can generate meaningful activation maps and associated descriptive signals, which are useful to evaluate datasets of the entire brain or selected portions of it. Besides computational implications, variations in the input dataset combined with the multivariate nature of ICA may lead to different spatial or temporal readouts of brain activation phenomena. By reducing and increasing a volume of interest (VOI), we applied sICA to different datasets from real activation experiments with multislice acquisition and single or multiple sensory‐motor task‐induced blood oxygenation level‐dependent (BOLD) signal sources with different spatial and temporal structure. Using receiver operating characteristics (ROC) methodology for accuracy evaluation and multiple regression analysis as benchmark, we compared sICA decompositions of reduced and increased VOI fMRI time‐series containing auditory, motor and hemifield visual activation occurring separately or simultaneously in time. Both approaches yielded valid results; however, the results of the increased VOI approach were spatially more accurate compared to the results of the decreased VOI approach. This is consistent with the capability of sICA to take advantage of extended samples of statistical observations and suggests that sICA is more powerful with extended rather than reduced VOI datasets to delineate brain activity. Hum Brain Mapp, 2005. © 2006 Wiley‐Liss, Inc.

Published
2006
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34. Hepatitis B surface antigen genetic elements critical for immune escape correlate with hepatitis B virus reactivation upon immunosuppression

Author

Matteo Surdo, L. Carioti, Maria Concetta Bellocchi, Valentina Svicher, Claudio Maria Mastroianni, M. Paoloni, Claudia Alteri, L. Colagrossi, Yoram Louzoun, Romina Salpini, Mariarosaria Esposito, Michela Pollicita, Carlo Federico Perno, Loredana Sarmati, Massimo Andreoni, Mario Angelico, Massimo Marignani, Cesare Sarrecchia, Chiara D'Amore, Marianna Aragri, Christina Becker, Fabiola Di Santo, Aldo Marrone, Miriam Lichtner, A. Ricciardi, Daniele Armenia, Jens Verheyen, Salpini, R, Colagrossi, L, Bellocchi, Mc, Surdo, M, Becker, C, Alteri, C, Aragri, M, Ricciardi, A, Armenia, D, Pollicita, M, Di Santo, F, Carioti, L, Louzoun, Y, Mastroianni, Cm, Lichtner, M, Paoloni, M, Esposito, M, D'Amore, C, Marrone, A, Marignani, M, Sarrecchia, C, Sarmati, L, Andreoni, M, Angelico, M, Verheyen, J, Perno, Cf, Svicher, V, Marrone, Aldo, Verhejen, J, and Svicher, V.

Subjects
Male, HBsAg, Glycosylation, medicine.medical_treatment, Medizin, medicine.disease_cause, genetic variability, HBV, education.field_of_study, immunosuppression, biology, virus diseases, Immunosuppression, surface antigen, Hepatitis B, Middle Aged, Settore MED/07 - Microbiologia e Microbiologia Clinica, Rituximab, Female, Antibody, medicine.drug, Adult, medicine.medical_specialty, Hepatitis B virus, Settore MED/17 - Malattie Infettive, Population, Hepatitis B, Chronic, Internal medicine, Drug Resistance, Viral, medicine, Humans, Hepatitis B Antibodies, education, Aged, Immune Evasion, Immunosuppression Therapy, Hepatitis B Surface Antigens, Hepatology, business.industry, medicine.disease, Virology, digestive system diseases, Immunology, Mutation, biology.protein, Virus Activation, business
Abstract

Hepatitis B virus (HBV) reactivation during immunosuppression can lead to severe acute hepatitis, fulminant liver failure, and death. Here, we investigated hepatitis B surface antigen (HBsAg) genetic features underlying this phenomenon by analyzing 93 patients: 29 developing HBV reactivation and 64 consecutive patients with chronic HBV infection (as control). HBsAg genetic diversity was analyzed by population-based and ultradeep sequencing (UDS). Before HBV reactivation, 51.7% of patients were isolated hepatitis B core antibody (anti-HBc) positive, 31.0% inactive carriers, 6.9% anti-HBc/anti-HBs (hepatitis B surface antibody) positive, 6.9% isolated anti-HBs positive, and 3.4% had an overt HBV infection. Of HBV-reactivated patients, 51.7% were treated with rituximab, 34.5% with different chemotherapeutics, and 13.8% with corticosteroids only for inflammatory diseases. In total, 75.9% of HBV-reactivated patients (vs. 3.1% of control patients; P

Published
2015

35. Evidence of Spontaneous Post-transplant HCV Eradication in Two Failed DAA Treatments Awaiting Liver Transplantation

Author

Francesca Ceccherini-Silberstein, Carlo Federico Perno, Martina Milana, A. Bosa, Francesco Paolo Antonucci, Ilaria Lenci, Marianna Aragri, Mario Angelico, Giuseppe Tisone, and Leonardo Baiocchi

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Physiology, medicine.medical_treatment, Remission, Spontaneous, 030230 surgery, Liver transplantation, Antiviral Agents, End Stage Liver Disease, 03 medical and health sciences, 0302 clinical medicine, Transplant surgery, Internal medicine, HCV eradication, Medicine, Humans, Treatment Failure, DAA treatment, Settore MED/12 - Gastroenterologia, business.industry, Liver Neoplasms, Gastroenterology, Hepatology, Hepatitis C, Chronic, Middle Aged, Viral Load, Settore MED/07 - Microbiologia e Microbiologia Clinica, Post transplant, Surgery, RNA, Viral, 030211 gastroenterology & hepatology, Female, business
Published
2017

36. Characterization of resistance profiles in HCV 2-3-4 DAA-naïve and DAA-experienced infected patients in Italy

Author

V. Boccaccio, Irene Maida, Ennio Polilli, Alessandro Ciaccio, Ilaria Lenci, Anna Claudia Pellicelli, Marilena Rendina, Fabio Niero, Guido Gubertini, Mario Angelico, T. Ruggiero, Stefano Bonora, Barbara Rossetti, Caterina Pasquazzi, Niccolò Gabriele Coppola, Simona Francioso, Silvia Barbaliscia, M. Puoti, M. Andreoni, L. Foroghi, L. Sarmati, Silvia Paolucci, Giuliana Fiorentino, Teresa Pollicino, G.B. Gaeta, C.F. Perno, Giustino Parruti, Valeria Cento, Laura Ambra Nicolini, Gloria Taliani, Elisabetta Teti, Lucio Boglione, Asia Bertoli, Sergio Babudieri, Valeria Micheli, Renato Maserati, Marianna Aragri, F. Ceccherini-Silberstein, Vincenzo Vullo, A. R. D’Ambrosio, Simona Marenco, A. Lleo, Antonio Craxì, Filomena Morisco, V.C. Di Maio, Vincenzo Sangiovanni, Maurizio Zazzi, Vincenza Calvaruso, Alessia Ciancio, V. Pace Palitti, Bianca Bruzzone, and Giacomo Raimondo

Subjects
Hepatology, business.industry, Gastroenterology, Medicine, business, Virology
Published
2018
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37. National quality control and validation of hepatitis C NS3, NS5A and NS5B genotypic resistance testing

Author

Valeria Cento, Maurizio Zazzi, Teresa Pollicino, Anna Rosa Garbuglia, S. Soldini, M. Arosio, Silvia Galli, A. Raddi, Annapaola Callegaro, Enzo Boeri, Marianna Aragri, Valeria Ghisetti, C. Minosse, N. Cuomo, Rosaria Santangelo, Daniela Cavallone, M. L. Vatteroni, Maurizia Rossana Brunetto, Nicola Coppola, Giuseppina Raffa, T. Santantonio, A. Lai, G. Raimondo, M. Di Stefano, C.F. Perno, Stefania Paolucci, Antonio Craxì, Valeria Micheli, William Gennari, T. Ruggiero, F. Ceccherini-Silberstein, E. Galmozzi, Mario Starace, Michela Sampaolo, Bianca Bruzzone, Laura Monno, Maria Rosaria Capobianchi, Maurizio Sanguinetti, C. Caudai, Stefano Menzo, and Fausto Baldanti

Subjects
0301 basic medicine, NS3, Hepatology, business.industry, media_common.quotation_subject, Gastroenterology, Hepatitis C, medicine.disease, Biotechnology, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, chemistry, medicine, Genotypic resistance, Quality (business), business, NS5A, NS5B, media_common
Published
2018
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38. Independent component model of the default-mode brain function: combining individual-level and population-level analyses in resting-state fMRI

Author

Elio Marciano, Gioacchino Tedeschi, Sossio Cirillo, Fabrizio Esposito, Adriana Aragri, Rainer Goebel, Francesco Di Salle, Ilaria Pesaresi, Cognitive Neuroscience, RS: FPN CN I, F., Esposito, A., Aragri, I., Pesaresi, S., Cirillo, G., Tedeschi, Marciano, Elio, R., Goebel, F., Di Salle, Esposito, F, Aragri, A, Pesaresi, I, Cirillo, Sossio, Tedeschi, Gioacchino, Marciano, E, Goebel, R, and DI SALLE, F.

Subjects
Adult, Elementary cognitive task, Computer science, Speech recognition, Image Processing, Functional magnetic resonance imaging, Biomedical Engineering, Biophysics, computer.software_genre, Brain mapping, methods, Correlation, Computer-Assisted, Voxel, blood, medicine, Image Processing, Computer-Assisted, 80 and over, Humans, Radiology, Nuclear Medicine and imaging, Resting state, Default mode network, Aged, Independent component analysi, Aged, 80 and over, Analysis of Variance, Brain Mapping, Resting state fMRI, medicine.diagnostic_test, business.industry, Adult, Aged, Aged, 80 and over, Analysis of Variance, Brain Mapping, methods, Brain, blood supply/physiology, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, methods, Middle Aged, Oxygen, fMRI, Brain, Pattern recognition, blood supply/physiology, Middle Aged, Independent component analysis, Magnetic Resonance Imaging, Oxygen, Default-mode network, Artificial intelligence, Group level analysis, business, computer
Abstract

Resting-state functional magnetic resonance imaging (RS-fMRI) is a technique used to investigate the spontaneous correlations of blood-oxygen-level-dependent signals across different regions of the brain. Using functional connectivity tools, it is possible to investigate a specific RS-fMRI network, referred to as "default-mode" (DM) network, that involves cortical regions deactivated in fMRI experiments with cognitive tasks. Previous works have reported a significant effect of aging on DM regions activity. Independent component analysis (ICA) is Often Used for generating spatially distributed DM Functional connectivity patterns front RS-fMRI data without the need for a reference region. This aspect and the relatively easy setup of an RS-fMRI experiment even in clinical trials have boosted the combined use of RS-fMRI and ICA-based DM analysis for noninvasive research of brain disorders, In this work, we considered different strategies for combining ICA results from individual-level and population-level analyses and used them to evaluate and predict the effect of aging on the DM component. Using RS-fMRI data from 20 normal subjects and a previously developed group-level ICA methodology, we generated group DM maps and showed that the overall ICA-DM connectivity is negatively correlated with age. A negative correlation of the ICA voxel weights with age existed in all DM regions at it variable degree. As an alternative approach, we generated a distributed DIM spatial template and evaluated the correlation of each individual DM component fit to this template with age. Using a "leave-one-out" procedure, we discuss the importance of removing the bias from the DM template-generation process.

Published
2008

39. Non-Inferential Multi-Subject Study of Functional Connectivity during Visual Stimulation

Author

Fabrizio Esposito, Adriana Aragri, Mario Cirillo, Luigi Cirillo, Sossio Cirillo, F. Di Salle, Ferdinando Caranci, Esposito, F, Cirillo, Mario, Aragri, A, Caranci, F, Cirillo, L, DI SALLE, F, Cirillo, Sossio, Esposito F, Cirillo M, Aragri A, Caranci F, Cirillo L, Di Salle F, and Cirillo S

Subjects
Multivariate statistics, Resting state fMRI, medicine.diagnostic_test, Computer science, Functional connectivity, Independent component analysis (ICA), functional magnetic resonance imaging (fMRI), Stimulation, General Medicine, Independent component analysis, Group analysis, Subject (grammar), medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Functional magnetic resonance imaging, Neuroscience
Abstract

Independent component analysis (ICA) is a powerful technique for the multivariate, non-inferential, data-driven analysis of functional magnetic resonance imaging (fMRI) data-sets. The non-inferential nature of ICA makes this a suitable technique for the study of complex mental states whose temporal evolution would be difficult to describe analytically in terms of classical statistical regressors. Taking advantage of this feature, ICA can extract a number of functional connectivity patterns regardless of the task executed by the subject. The technique is so powerful that functional connectivity patterns can be derived even when the subject is just resting in the scanner, opening the opportunity for functional investigation of the human mind at its basal “default” state, which has been proposed to be altered in several brain disorders. However, one major drawback of ICA consists in the difficulty of managing its results, which are not represented by a single functional image as in inferential studies. This produces the need for a classification of ICA results and exacerbates the difficulty of obtaining group “averaged” functional connectivity patterns, while preserving the interpretation of individual differences. Addressing the subject-level variability in the very same framework of “grouping” appears to be a favourable approach towards the clinical evaluation and application of ICA-based methodologies. Here we present a novel strategy for group-level ICA analyses, namely the self-organizing group-level ICA (sog-ICA), which is used on visual activation fMRI data from a block-design experiment repeated on six subjects. We propose the sog-ICA as a multi-subject analysis tool for grouping ICA data while assessing the similarity and variability of the fMRI results of individual subject decompositions.

Published
2006

40. Hepatitis C virus gene sequencing as a tool for precise genotyping in the era of new direct antiviral agents

Author

Carlo Federico Perno, Valeria Cento, Marianna Aragri, Velia Chiara Di Maio, Marco Ciotti, and Francesca Ceccherini Silberstein

Subjects
0301 basic medicine, Genotyping Techniques, Hepatology, Sequence Analysis, RNA, business.industry, Hepatitis C virus, Hepacivirus, medicine.disease_cause, Settore MED/07 - Microbiologia e Microbiologia Clinica, Virology, DNA sequencing, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine, 030211 gastroenterology & hepatology, Molecular Targeted Therapy, business, Genotyping
Published
2016

41. Effect of Carbonation on Brain Processing of Sweet Stimuli in Humans

Author

Giovanni Sarnelli, Maurizio Iengo, Francesco Di Salle, Maria Savarese, Elena Cantone, Anna Prinster, Adriana Aragri, Maxime E. Buyckx, Emanuele Nicolai, Rosario Cuomo, Di Salle, F, Cantone, Elena, Savarese, Mf, Aragri, A, Prinster, Anna, Nicolai, E, Sarnelli, Giovanni, Iengo, Maurizio, Buyckx, M, Cuomo, Rosario, Cognitive Neuroscience, and RS: FPN CN 2

Subjects
Sucrose, Taste, Carbonation, Thiazines, Carbonated Beverages, Amygdala, Article, ACTIVATION, taste, chemistry.chemical_compound, FOOD, medicine, Humans, Food science, Aspartame, functional imaging, Hepatology, medicine.diagnostic_test, Beverage Consumption, fMRI, digestive, oral, and skin physiology, Gastroenterology, Taste Perception, Brain, Carbon Dioxide, carbonated beverage, Magnetic Resonance Imaging, Artificial Sweetener, Gustatory System, Functional imaging, medicine.anatomical_structure, chemistry, Sweetening Agents, Orbitofrontal cortex, Functional magnetic resonance imaging
Abstract

Little is known about how CO2 affects neural processing of taste. We used functional magnetic resonance imaging to investigate the effects of carbonation on brain processing of sweet stimuli, which has relevance to studies of food selection and satiety. The presence of carbonation produced an overall decrease in the neural processing of sweetness-related signals, especially from sucrose. CO2 reduced the neural processing of sucrose more than that of artificial sweeteners. These findings might be relevant to dietary interventions that include noncaloric beverages, whereas the combination of CO2 and sucrose might increase consumption of sucrose.

Published
2013

42. Prevalence and characteristics of resistance associated substitutions in DAA-naive and DAA-failed HCV-3 patients in Italy

Author

V.C. Di Maio, S. Barbaliscia, I. Lenci, E. Teti, F.P. Antonucci, V. Cento, M. Aragri, S. Paolucci, B. Bruzzone, N. Coppola, T. Ruggiero, T. Pollicino, E. Polilli, C. Pasquazzi, V. Pace Palitti, C.F. Magni, V. Micheli, A. Di Biagio, L. Sticchi, M. Melis, S. Francioso, C. Masetti, L. Foroghi, C. Sarrecchia, L. Baiocchi, S. Landonio, A. Bertoli, V. Calvaruso, F. Morisco, I. Maida, S. Marenco, A. Leo, V. Ghisetti, A. Ciancio, P. Sacchi, S. Novati, G. Brancaccio, A. Pieri, M. Puoti, P. Toniutto, V. Vullo, A. Aghemo, G. Di Perri, S. Babudieri, G. Rizzardini, S. Bruno, A. Pellicelli, G. Taliani, G. Raimondo, F. Baldanti, G.B. Gaeta, A. Craxì, G. Parruti, M. Andreoni, M. Angelico, C.F. Perno, and F. Ceccherini-Silberstein

Subjects
Hepatology, Resistance (ecology), business.industry, Gastroenterology, Medicine, business, Virology
Published
2017
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43. Multiclass HCV resistance to interferon-free direct acting antivirals regimens in real life failures advocates for tailored second-line therapies

Author

Ilaria Lenci, A. Di Biagio, Giuliano Rizzardini, L. Marinaro, C. D'Ambrosio, Fausto Baldanti, Ivana Maida, G.B. Gaeta, M. Puoti, T. Ruggiero, Mario Angelico, Vincenza Calvaruso, Laura Sticchi, Mario Starace, Giustino Parruti, P. Cacciatore, Nicola Caporaso, Caterina Pasquazzi, Stefania Paolucci, Anna Claudia Pellicelli, M. Andreoni, C. Masetti, Sergio Babudieri, Gabriella d'Ettorre, Francesco Santopaolo, Raffaele Cozzolongo, P. Andreone, Carlo Magni, Valeria Cento, Guido Gubertini, J. Vecchiet, Stefano Novati, Nicola Coppola, C.F. Perno, Bianca Bruzzone, F. De Leonardis, V. Pace Palitti, Marianna Aragri, A. Grieco, Pierluigi Tarquini, G. De Stefano, G. Raimondo, Teresa Pollicino, Alessia Giorgini, Giorgio Barbarini, Valeria Ghisetti, G. Verucchi, M.C. Sorbo, Savino Bruno, M. Paoloni, F. Ceccherini-Silberstein, Roberto Gulminetti, Antonio Craxì, Filomena Morisco, Manuela Merli, V.C. Di Maio, Vincenzo Sangiovanni, A. Ciancio, Simona Francioso, Simona Landonio, Aldo Bertoli, A. Mancon, Valeria Micheli, Antonio Picciotto, V. Boccaccio, M. Melis, Ennio Polilli, F.P. Antonucci, Dante Romagnoli, and Silvia Barbaliscia

Subjects
Oncology, medicine.medical_specialty, Hepatology, business.industry, Interferon free, Gastroenterology, DIRECT ACTING ANTIVIRALS, 03 medical and health sciences, 0302 clinical medicine, Second line, 030220 oncology & carcinogenesis, Internal medicine, Medicine, In real life, 030211 gastroenterology & hepatology, business
Published
2017
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44. The challenge of HCV-retreatment after DAA-failure: real-life experience advocates for caution

Author

Vincenza Calvaruso, C. Masetti, Silvia Barbaliscia, Bianca Bruzzone, Giustino Parruti, Sergio Babudieri, Marco Biolato, Marianna Aragri, C.F. Perno, Vincenzo Messina, Valeria Cento, Simona Landonio, M. Melis, Carmine Minichini, Valeria Micheli, F. Ceccherini-Silberstein, Lucio Boglione, Giorgio Barbarini, Mario Angelico, Aldo Bertoli, Monica Schiavini, Laura Ambra Nicolini, Ennio Polilli, Raffaele Cozzolongo, Carlo Magni, Chiara Baiguera, C. Dentone, Giuliano Rizzardini, Anna Claudia Pellicelli, M. Siciliano, Y. Troshina, Antonio Craxì, Filomena Morisco, M. Puoti, V.C. Di Maio, A. Ciancio, Ilaria Lenci, Laura Sticchi, Stefania Paolucci, T. Ruggiero, Simona Marenco, and Nicola Coppola

Subjects
0301 basic medicine, 03 medical and health sciences, medicine.medical_specialty, 030104 developmental biology, 0302 clinical medicine, Hepatology, business.industry, Immunology, medicine, 030211 gastroenterology & hepatology, Intensive care medicine, business
Published
2017
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45. Multiclass hepatitis C virus resistance to direct acting antivirals in real life interferon-free regimens failures advocates for tailored second-line therapies

Author

A. Grieco, Valeria Cento, Savino Bruno, M. Paoloni, Anna Claudia Pellicelli, Gabriella d'Ettorre, Raffaele Cozzolongo, G.D. Stefano, Carlo Magni, V. Boccaccio, M. Andreoni, Fausto Baldanti, Silvia Barbaliscia, J. Vecchiet, Valeria Micheli, Antonio Picciotto, Giustino Parruti, Guido Gubertini, M. Melis, Pierluigi Tarquini, Francesca Ceccherini-Silberstein, Bianca Bruzzone, Sergio Babudieri, Antonio Di Biagio, M. Puoti, Manuela Merli, L. Marinaro, Mario Starace, Caterina Pasquazzi, Marianna Aragri, Antonio Craxì, Teresa Pollicino, Filomena Morisco, V.C. Di Maio, Alessia Giorgini, Vincenzo Sangiovanni, Giorgio Barbarini, Valeria Ghisetti, G. Verucchi, T. Ruggiero, Ivana Maida, P. Andreone, Vincenza Calvaruso, Giovanni Raimondo, C. D'Ambrosio, Simona Francioso, F.P. Antonucci, Dante Romagnoli, C.F. Perno, Mario Angelico, Ilaria Lenci, Alessia Ciancio, Roberto Gulminetti, G.B. Gaeta, Simona Landonio, Nicola Caporaso, Francesco Santopaolo, Nicola Coppola, Laura Sticchi, Valeria Pace Palitti, Stefania Paolucci, Aldo Bertoli, and A. Mancon

Subjects
0301 basic medicine, Hepatology, business.industry, Hepatitis C virus, Interferon free, medicine.disease_cause, DIRECT ACTING ANTIVIRALS, Virology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Second line, medicine, In real life, 030211 gastroenterology & hepatology, business
Published
2017
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46. The role of a pre-load beverage on gastric volume and food intake: comparison between non-caloric carbonated andnon-carbonated beverage

Author

Viviana Verlezza, Maria Savarese, Emanuele Nicolai, F.P. Zito, Giovanni Sarnelli, Rosario Cuomo, E. Efficie, L. Vozzella, Adriana Aragri, Maxime E. Buyckx, Carla Cirillo, Cuomo, Rosario, Savarese, Mf, Sarnelli, Giovanni, Nicolai, E, Aragri, A, Cirillo, Carla, Vozzella, L, Zito, Fp, Verlezza, V, Efficie, Eleonora, and Buyckx, M.

Subjects
Male, calorie intake, liquid meal, Drinking, Medicine (miscellaneous), lcsh:TX341-641, Carbonated Beverages, Clinical nutrition, Satiation, solid meal, Satiety Response, Beverages, chemistry.chemical_compound, Young Adult, Medicine, Humans, Carbonated beverage, Food science, gastric volume, lcsh:RC620-627, Cholecystokinin, Meal, Nutrition and Dietetics, business.industry, Stomach, Research, digestive, oral, and skin physiology, Organ Size, cholecystokinin, Magnetic Resonance Imaging, Preload, lcsh:Nutritional diseases. Deficiency diseases, medicine.anatomical_structure, chemistry, Biochemistry, Gastric physiology, ghrelin, Carbon dioxide, Ghrelin, Female, Analysis of variance, business, Energy Intake, lcsh:Nutrition. Foods and food supply
Abstract

Background There is conflicting data on the effects of carbon dioxide contained in beverages on stomach functions. We aimed to verify the effect of a pre-meal administration of a 300 ml non-caloric carbonated beverage (B+CO2) compared to water or a beverage without CO2 (B-CO2), during a solid (SM) and a liquid meal (LM) on: a) gastric volume, b) caloric intake, c) ghrelin and cholecystokinin (CCK) release in healthy subjects. Methods After drinking the beverages (Water, B-CO2, B+CO2), ten healthy subjects (4 women, aged 22-30 years; BMI 23 ± 1) were asked to consume either an SM or an LM, at a constant rate (110 kcal/5 min). Total gastric volumes (TGV) were evaluated by Magnetic Resonance Imaging after drinking the beverage and at maximum satiety (MS). Total kcal intake at MS was evaluated. Ghrelin and CCK were measured by enzyme immunoassay until 120 min after the meal. Statistical calculations were carried out by paired T-test and analysis of variance (ANOVA). The data is expressed as mean ± SEM. Results TGV after B+CO2 consumption was significantly higher than after B-CO2 or water (p < 0.05), but at MS, it was no different either during the SM or the LM. Total kcal intake did not differ at MS after any of the beverages tested, with either the SM (Water: 783 ± 77 kcals; B-CO2: 837 ± 66; B+CO2: 774 ± 66) or the LM (630 ± 111; 585 ± 88; 588 ± 95). Area under curve of ghrelin was significantly (p < 0.05) lower (13.8 ± 3.3 ng/ml/min) during SM following B-CO2 compared to B+CO2 and water (26.2 ± 4.5; 27.1 ± 5.1). No significant differences were found for ghrelin during LM, and for CCK during both SM and LM after all beverages. Conclusions The increase in gastric volume following a 300 ml pre-meal carbonated beverage did not affect food intake whether a solid or liquid meal was given. The consistency of the meal and the carbonated beverage seemed to influence ghrelin release, but were unable, under our experimental conditions, to modify food intake in terms of quantity. Further studies are needed to verify if other food and beverage combinations are able to modify satiation.

Published
2011

47. Hepatitis C virus RNA levels at week-2 of telaprevir/boceprevir administration are predictive of virological outcome

Author

Marianna Aragri, Lorenzo Nosotti, Ilaria Lenci, Massimo Siciliano, Francesco De Leonardis, Massimo Andreoni, Mario Angelico, Carlo Magni, Domenico Di Carlo, Alessandro Mancon, Sergio Babudieri, Cesare Sarrecchia, Adriano Gasbarrini, Francesca Ceccherini-Silberstein, Gloria Taliani, Simona Landonio, Giustino Parruti, Antonio Di Biagio, Velia Chiara Di Maio, M. Tontodonati, Francesco Paolo Antonucci, Valeria Micheli, Valeria Cento, Maria Stella Mura, Carlo Federico Perno, Daniele Di Paolo, Giuliano Rizzardini, Adriano M. Pellicelli, Jacopo Vecchiet, A. Manunta, and Laura Ambra Nicolini

Subjects
Male, NS3 protease inhibitors, Hepacivirus, Drug resistance, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, Telaprevir, chemistry.chemical_compound, Viral, Chronic, Early response, Viral kinetics, Virological failure, education.field_of_study, biology, Middle Aged, Viral Load, Prognosis, Settore MED/07 - Microbiologia e Microbiologia Clinica, Hepatitis C, Treatment Outcome, Combination, RNA, Viral, Drug Therapy, Combination, Female, Oligopeptides, Viral load, medicine.drug, Adult, medicine.medical_specialty, Proline, Settore MED/12 - GASTROENTEROLOGIA, Hepatitis C virus, Population, Antiviral Agents, Drug Therapy, Boceprevir, Internal medicine, Ribavirin, medicine, Humans, education, Hepatology, business.industry, Interferon-alpha, Hepatitis C, Chronic, biology.organism_classification, chemistry, Immunology, RNA, business
Abstract

Triple therapy with telaprevir/boceprevir + pegylated-interferon+ribavirin can achieve excellent antiviral efficacy, but it can be burdened with resistance development at failure.To evaluate kinetics of hepatitis C virus (HCV) RNA decay and early resistance development, in order to promptly identify patients at highest risk of failure to first generation protease inhibitors.HCV-RNA was prospectively quantified in 158 patients receiving pegylated-interferon+ribavirin+telaprevir (N = 114) or+boceprevir (N = 44), at early time-points and during per protocol follow-up. Drug resistance was contextually evaluated by population sequencing.HCV-RNA at week-2 was significantly higher in patients experiencing virological failure to triple-therapy than in patients with sustained viral response (2.3 [1.9-2.8] versus 1.2 [0.3-1.7]log IU/mL, p0.001). A 100 IU/mL cut-off value for week-2 HCV-RNA had the highest sensitivity (86%) in predicting virological success. Indeed, 23/23 (100%) patients with undetectable HCV-RNA reached success, versus 26/34 (76.5%) patients with HCV-RNA100 IU/mL, and only 11/31 (35.5%) with HCV-RNA100 IU/mL (p0.001). Furthermore, differently from failing patients, none of the patient with undetectable HCV-RNA at week-2 had baseline/early resistance.With triple therapy based on first generation protease inhibitors, suboptimal HCV-RNA decay at week-2 combined with early detection of resistance can help identifying patients with higher risk of virological failure, thus requiring a closer monitoring during therapy.

Published
2015

48. Slow achievement of HCV-RNA undetectability in cirrhotic patients treated with sofosbuvir+ribavirin: possible clinical implications in the liver transplant list management

Author

V.C. Di Maio, Francesca Ceccherini-Silberstein, Ilaria Lenci, Luciano Milanesi, Maria Chiara Colombo, M. Manuelli, Maria Francesca Donato, A. Castellaneta, Roberta Alfieri, M. Rendina, Martina Milana, Maria Laura Ponti, R. Canu, A. Di Leo, C.F. Perno, R. Ganga, Federica Malinverno, S. Monico, Mario Angelico, Valeria Cento, Daniele Sforza, Marianna Aragri, A. Abedrabbo, and Giuseppe Tisone

Subjects
chemistry.chemical_compound, medicine.medical_specialty, Hepatology, chemistry, Sofosbuvir, business.industry, Ribavirin, Internal medicine, Gastroenterology, medicine, business, medicine.drug
Abstract

Sofosbuvir (SOF) treatment ± ribavirin (RBV) prior to LT has the potential to change the HCV recurrence after Liver Transplantation (LT). This approach has been reported to avoid graft reinfection in compensated patients with hepatocellular carcinoma (HCC), but only among those who reached and maintained undetectable HCV-RNA (TND) before LT. Since the time to obtain this result in decompensated cirrhotics is unknown, we sought to investigate the early HCV-RNA decay in this setting. Sixteen decompensated patients (M/F 12/4, median age 55.3, CPT score>=B7), infected by HCV genotype 1a, 1b, 3 and 4 (2-8- 4-2), 4 of whom with HCC, were treated with SOF 400mg/day and RBV (200-1000 mg/day), except 2 who received SOF alone, for a median(IQR) of 12(11-16) weeks awaiting LT. HCV-RNA levels were measured weekly and safety and clinical parameters were analyzed. No serious adverse events were reported. The median(IQR) RBV dose was 600(400-800). Despite 11/16 patients had low baseline viremia (

Published
2015
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49. Distributed analysis of simultaneous EEG-fMRI time-series: modeling and interpretation issues

Author

Tommaso Piccoli, Gioacchino Tedeschi, Adriana Aragri, Rainer Goebel, Francesco Di Salle, Fabrizio Esposito, Esposito, F, Aragri, A, Piccoli, T, Tedeschi, G, Goebel, R, Di Salle, F, Cognitive Neuroscience, RS: FPN CN I, Tedeschi, Gioacchino, and DI SALLE, F.

Subjects
Male, Default-mode, Brain activity and meditation, Computer science, instrumentation/methods, Electroencephalography, computer.software_genre, Synchronization, Computer-Assisted, Models, EEG, Evoked Potentials, Default mode network, Parametric statistics, Visual Cortex, Brain Mapping, medicine.diagnostic_test, fMRI, Settore MED/37 - Neuroradiologia, Magnetic Resonance Imaging, Pattern Recognition, Visual, Neurological, Visual, Adult, Models, Neurological, Biomedical Engineering, Biophysics, Pattern Recognition, Machine learning, EEG-fMRI, Sensitivity and Specificity, methods, Image Interpretation, Computer-Assisted, medicine, Humans, Radiology, Nuclear Medicine and imaging, Computer Simulation, Image Interpretation, business.industry, Working memory, Reproducibility of Results, Pattern recognition, Adult, Brain Mapping, methods, Computer Simulation, Electroencephalography, methods, Evoked Potentials, physiology, Humans, Image Interpretation, methods, Magnetic Resonance Imaging, instrumentation/methods, Male, Models, Neurological, Pattern Recognition, physiology, Reproducibility of Results, Sensitivity and Specificity, Visual Cortex, physiology, Distributed source modeling, Evoked Potentials, Visual, Artificial intelligence, business, Functional magnetic resonance imaging, computer
Abstract

Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) represent brain activity in terms of a reliable anatomical localization and a detailed temporal evolution of neural signals. Simultaneous EEG-fMRI recordings offer the possibility to greatly enrich the significance and the interpretation of the single modality results because the same neural processes are observed from the same brain at the same time. Nonetheless, the different physical nature of the measured signals by the two techniques renders the coupling not always straightforward, especially in cognitive experiments where spatially localized and distributed effects coexist and evolve temporally at different temporal scales. The purpose of this article is to illustrate the combination of simultaneously recorded EEG and fMRI signals exploiting the principles of EEG distributed source modeling. We define a common source space for fMRI and EEG signal projection and gather a conceptually unique framework for the spatial and temporal comparative analysis. We illustrate this framework in a graded-load working-memory simultaneous EEG-fMRI experiment based on the n-back task where sustained load-dependent changes in the blood-oxygenation-level-dependent (BOLD) signals during continuous item memorization co-occur with parametric changes in the EEG theta power induced at each single item. In line with previous studies, we demonstrate on two single-subject cases how the presented approach is capable of colocalizing in midline frontal regions two phenomena simultaneously observed at different temporal scales, such as the sustained negative changes in BOLD activity and the parametric EEG theta synchronization. We discuss the presented approach in relation to modeling and interpretation issues typically arising in simultaneous EEG-fMRI studies.

Published
2009

50. Meal form influences CCK release and maximum satiation in healthy subjects

Author

A. Aragri, G. Vollono, Luigi Russo, Maria Savarese, R. Cuomo, F. De Giorgi, G. Sarnelli, Carla Cirillo, Savarese, Mf, Sarnelli, Giovanni, Aragri, A., Vollono, G., Cirillo, C., De Giorgi, F., Russo, L., and Cuomo, Rosario

Subjects
Meal, medicine.medical_specialty, Endocrinology, Hepatology, business.industry, Internal medicine, CCK release, Gastroenterology, Healthy subjects, maximum satiation, Medicine, business
Abstract

Background and aim: Meal-induced gastric distension and Cholecys- tokinin (CCK) are involved in the food intake. The relationship between meal gastric distension and CCK release have not been studied by non- invasive technique. We studied gastric volumes changes by Magnetic Resonance Imaging (MRI) and CCK serum levels after water preload and liquid (LM) and solid (SM) meals. Material and methods: Ten healthy subjects (4 F; Age 22 ± 3; BMI 23 ± 1) were studied on two days. Two test meals, a SM and LM with a similar nutrient composition (carbohydrate 46%; fat 32%; protein 22%) and energy content were used. Subjects were requested to ingest constant Kcal at 5 min interval (100 kcal/5 min) and to score their satiation level on a visual analogue scale graded 0–5 (1=threshold, 5= maximum satiation- MS). Experiment was scheduled as following: -10 min: 300 ml water preload (WPL); 0 min: solid or liquid meal until MS. CCK levels (ELISA, Phoenix, USA) were measured at baseline, after WPL, at 30, 60, 120 min of meal test. Gastric volume was evaluated by 1.5 T MRI at baseline, after water load, at MS and 120 min. Total (TGV) and proximal (PGV) gastric volumes (as difference respect to baseline) were manually traced by a trained observer. Data are presented as mean ± SD. Results: Kcal ingested and time to reach MS were significantly higher during SM (783 ± 244 kcal; 44 ± 14 min) than LM (630 ± 353 p < 0.01; 31 ± 17 p < 0.01). CCK serum peaks and time to peak were not different in LM and SM (1.62 ± 0.72 ng/ml vs 1.26 ± 0.87, and 41 ± 21 min vs 39 ± 14, respectively). TGV and PGV were not different between the two meal groups after WPL (SM: 271 ± 59 ml, 72 ± 46 vs LM: 309 ± 55, 74 ± 29) and at MS (SM: 554 ± 203 ml, 92 ± 32 vs LM: 560 ± 301, 132 ± 60). However TGV after WPL significantly correlated with CCK peaks in both meal groups (SM: r=0.73; p=0.016 and LM: r=0.62; p=0.049). PGV correlated with CCK peak in LM but not in SM (r=0.72, p=0.015; r=0.026, p=0.82). Conclusions: The MS induced by SM is not depending by GV and by CCK release. In contrast, the ability of LM to induce an earlier satiation is associated to the combined effect of the proximal stomach distension and the maximum CCK release. These results suggest a partial role of both total and proximal gastric distension in to determine CCK release. This relationship appears more evident with a liquid form of meal

Published
2009

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