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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. 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: Romina Salpini, Lorenzo Piermatteo, Arianna Battisti, Luna Colagrossi, Marianna Aragri, Katia Yu La Rosa, Ada Bertoli, Patrizia Saccomandi, Miriam Lichtner, Massimo Marignani, Sarah Maylin, Constance Delaugerre, Filomena Morisco, Nicola Coppola, Aldo Marrone, Nerio Iapadre, Carlotta Cerva, Stefano Aquaro, Mario Angelico, Loredana Sarmati, Massimo Andreoni, Jens Verheyen, Francesca Ceccherini-Silberstein, Massimo Levrero, Carlo Federico Perno, Laura Belloni, and Valentina Svicher
Subjects: hbv, hbv reactivation, hbsag, n-linked glycosylation, Microbiology, QR1-502
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 [5.3−8.0] logIU/mL, 23.4% of patients remained HBsAg-negative. HBsAg-negativity at HBV-reactivation correlated with the presence of >1 additional NLGSs (p < 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
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3. NS5A Gene Analysis by Next Generation Sequencing in HCV Nosocomial Transmission Clusters of HCV Genotype 1b Infected Patients

Author: Maria Concetta Bellocchi, Marianna Aragri, Luca Carioti, Lavinia Fabeni, Rosaria Maria Pipitone, Giuseppina Brancaccio, Maria Chiara Sorbo, Silvia Barbaliscia, Velia Chiara Di Maio, Fabrizio Bronte, Stefania Grimaudo, Walter Mazzucco, Ferdinando Frigeri, Marco Cantone, Antonio Pinto, Carlo Federico Perno, Antonio Craxì, Giovanni Battista Gaeta, Vito Di Marco, and Francesca Ceccherini-Silberstein
Subjects: HCV, acute infection, chronic infection, nosocomial transmission, sequencing, NGS, Cytology, QH573-671
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 β-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 β-thalassemia-patients and three involving both HCV-acute and chronic β-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 < 0.05). Even though Shannon-entropy was higher in chronic-patients, significantly higher values were observed only in chronic β-thalassemia-patients versus acute β-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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4. 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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5. 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

6. 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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7. 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

8. 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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9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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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16. 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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17. 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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18. SAT-190-Specific genetic elements in HBsAg C-terminus profoundly affect HBsAg levels in vivo, hamper HBsAg secretion in vitro and alter HBsAg structural stability in HBeAg-negative chronic HBV genotype D infection

Author: Patrick T F Kennedy, Ada Bertoli, Carlo Federico Perno, Massimo Marignani, Jens Verheyen, Paoloni Maurizio, L. Carioti, T. Mari, Vincenzo Malagnino, Carlotta Cerva, L. Colagrossi, Angelico Mario, Giustino Parruti, Jacopo Vecchiet, A. Battisti, Francesca Ceccherini Silberstein, A. Iuvara, Olympia E. Anastasiou, Upkar S. Gill, Claudio Maria Mastroianni, Miriam Lichtner, L. Piermatteo, Giuseppe Maria De Sanctis, Caterina Pasquazzi, Romina Salpini, Sandro Grelli, Massimo Andreoni, N. Iapadre, Loredana Sarmati, Marianna Aragri, and Valentina Svicher
Subjects: HBsAg, Hepatology, Hbeag negative, In vivo, C-terminus, Hbv genotype, Secretion, Biology, Affect (psychology), Virology, In vitro
Published: 2019
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19. 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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20. 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

21. 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

22. 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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23. 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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24. 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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25. 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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26. 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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27. Key mutational patterns in HBsAg C-terminus profoundly affect HBsAg levels in HBeAg-negative chronic HBV genotype D infection

Author: A. Battisti, Olympia E. Anastasiou, Giuseppe Maria De Sanctis, Lavinia Fabeni, Caterina Pasquazzi, L. Carioti, Patrick T F Kennedy, Domenico Di Carlo, T. Mari, Jens Verheyen, Sandro Grelli, V. Svicher, Mario Angelico, J. Vecchiet, R. Salpini, M. Andreoni, L. Sarmati, Luna Colagrossi, A. Iuvara, Marianna Aragri, M. Lichtner, Giustino Parruti, Massimo Marignani, Aldo Bertoli, L. Piermatteo, V. Fini, Carlotta Cerva, U.S. Gill, Claudio Maria Mastroianni, Francesca Ceccherini Silberstein, P. Maurizio, C.F. Perno, Vincenzo Malagnino, and N. Iapadre
Subjects: HBsAg, Hepatology, Hbeag negative, C-terminus, Medizin, Hbv genotype, Biology, Affect (psychology), Virology
Published: 2018
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28. 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

29. 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

30. 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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31. 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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32. 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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33. 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

34. 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

35. 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

36. In the ERA of New Direct Acting Antiviral Agents HCV Sequencing Allows the Most Accurate Subtype and Genotype Assignment

Author: A. Manunta, A. Grieco, Lorenzo Nosotti, D. Di Paolo, Gloria Taliani, Umberto Vespasiani Gentilucci, Carlo Magni, L. Lambiase, Simona Landonio, M. Tontodonati, A. Di Biagio, C.F. Perno, F.P. Antonucci, Gabriella d'Ettorre, Valeria Cento, S. Grieco, Maria Stella Mura, Francesca Ceccherini Silberstein, Cesare Sarrecchia, Dante Romagnoli, Elisabetta Teti, Laura Gianserra, Miriam Lichtner, Giustino Parruti, Aldo Bertoli, F. De Leonardis, Adriano M. Pellicelli, P. Cacciatore, Claudio Maria Mastroianni, Laura Ambra Nicolini, M. Andreoni, Antonio Gasbarrini, Simona Francioso, Sergio Babudieri, Simona Marenco, J. Vecchiet, Martina Milana, Mario Angelico, Caterina Pasquazzi, Ivana Maida, Ilaria Lenci, Valeria Micheli, Antonio Picciotto, Marianna Aragri, Marco Romano, E. D’Amico, Giuliano Rizzardini, Filomena Morisco, V.C. Di Maio, M. Siciliano, Savino Bruno, Marco Ciotti, and M. Puoti
Subjects: Genetics, 03 medical and health sciences, PRECLINICAL CHARACTERISATION OF JNJ-54257099 – A POTENT URIDINE-BASED NUCLEOTIDE POLYMERASE INHIBITOR IN PHASE I CLINICAL DEVELOPMENT FOR THE TREATMENT OF CHRONIC HEPATITIS C, 0302 clinical medicine, Hepatology, 030220 oncology & carcinogenesis, Genotype, 030211 gastroenterology & hepatology, Biology, Direct acting
Published: 2016

37. 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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38. 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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39. 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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40. 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

41. HBsAg genetic elements critical for immune escape correlate with HBV-reactivation upon immunosuppression

Author: Romina, Salpini, Luna, Colagrossi, Maria Concetta Bellocchi, Matteo, Surdo, Christina, Becker, Claudia, Alteri, Marianna, Aragri, Alessandra, Ricciardi, Daniele, Armenia, Michela, Pollicita, Fabiola Di Santo, Luca, Carioti, Yoram, Louzoun, Mastroianni, Claudio Maria, Lichtner, Miriam, Maurizio, Paoloni, Mariarosaria, Esposito, Chiara, D'Amore, Aldo, Marrone, Massimo, Marignani, Cesare, Sarrecchia, Loredana, Sarmati, Massimo, Andreoni, Mario, Angelico, Jens, Verhejen, Carlo Federico Perno, and Valentina, Svicher
Subjects: virus reactivation, hepatitis b virus, hepatitis b
Published: 2015

42. SLOW ACHIEVEMENT OF HCV-RNA UNDETECTABILITY IN CIRRHOTIC PATIENTS TREATED WITH SOFOSBUVIR plus RIBAVIRIN: POSSIBLE CLINICAL IMPLICATIONS IN THE LIVER TRANSPLANT LIST MANAGEMENT

Author: Sforza, Daniele, Lenci, Ilaria, Manuelli, Matteo, Cento, Valeria, Rendina, Maria, Maria, Francesca Donato, Martina, Milana, Marianna, Aragri, Velia, Chiara Di Maio, Amal, Abedrabbo, Federico, Malinverno, Sara, Monico, Maria, Laura Ponti, Roberta, Canu, Roberto, Ganga, Milanesi, Luciano, Di Leo, Alfredo, Perno, Carlo Federico, Ceccherini-Silberstein, Francesca, Colombo, Massimo, Angelico, Mario, and Tisone, Giuseppe
Subjects: Transplantation, HCV-RNA, virus diseases, hepatocellular carcinoma, digestive system diseases
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.
Published: 2015

43. 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

44. 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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45. Clinical relevance of accurate HCV genotype and subtype assignment by NS3/NS5A/NS5B direct sequencing in the era of new direct acting antiviral agents

Author: Carlo Magni, Francesca Ceccherini-Silberstein, M. Puoti, Claudio Maria Mastroianni, A. Di Biagio, Marco Romano, Filomena Morisco, Giustino Parruti, Antonio Gasbarrini, Gloria Taliani, M. Siciliano, Simona Landonio, V.C. Di Maio, Martina Milana, Laura Gianserra, F. Deodati, Caterina Pasquazzi, M. Andreoni, J. Vecchiet, Valeria Cento, L. Lambiase, Marianna Aragri, Simona Francioso, E. D’Amico, Gabriella d'Ettorre, Giuliano Rizzardini, D. Di Paolo, Antonio Grieco, F. De Leonardis, A. Manunta, Ivana Maida, Anna Claudia Pellicelli, Mario Angelico, K. Yu La Rosa, Miriam Lichtner, P. Cacciatore, Cesare Sarrecchia, F.P. Antonucci, Aldo Bertoli, Valeria Micheli, Antonio Picciotto, Dante Romagnoli, Savino Bruno, Laura Ambra Nicolini, Ilaria Lenci, C.F. Perno, Marco Ciotti, Lorenzo Nosotti, Simona Marenco, Elisabetta Teti, M. Tontodonati, Maria Stella Mura, R. Campoli, Nicola Caporaso, S. Grieco, Sergio Babudieri, and Umberto Vespasiani-Gentilucci
Subjects: Genetics, chemistry.chemical_compound, NS3, Hepatology, chemistry, Direct sequencing, Genotype, Gastroenterology, Clinical significance, Biology, NS5A, NS5B, Direct acting
Published: 2016
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46. Presence of resistance associated variants in patients with virological failure to new direct acting antivirals and requirement of unconventional regimens for re-treatment

Author: Antonio Craxì, Filomena Morisco, M. Puoti, V.C. Di Maio, Nicola Caporaso, Anna Claudia Pellicelli, Francesca Ceccherini-Silberstein, M. Paoloni, Maria Stella Mura, G.B. Gaeta, F.P. Antonucci, Vincenza Calvaruso, R. Campoli, Gianluca Brancaccio, D. Di Paolo, Dante Romagnoli, Antonio Grieco, K. Yu La Rosa, Stefano Brillanti, Valeria Cento, Caterina Pasquazzi, Ilaria Lenci, Manuela Merli, Simona Francioso, M.C. Sorbo, M. Melis, Marco Biolato, C.F. Perno, Marianna Aragri, Aldo Bertoli, Gabriella Verucchi, Sergio Babudieri, V. Pisani, Mario Angelico, Francesca Donato, and J. Vecchiet
Subjects: Oncology, medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, DIRECT ACTING ANTIVIRALS, Virological failure, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, 030211 gastroenterology & hepatology, In patient, business
Published: 2016
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47. P0912 : Early-phase HCV kinetics and role of pre-existing resistance in cirrhotic or interferon-insensitive patients on daclatasvir plus asunaprevir

Author: Francesca Ceccherini-Silberstein, Valeria Cento, Roberta Alfieri, F.P. Antonucci, Antonio Picciotto, Vincenza Calvaruso, S. Petta, Marianna Aragri, Antonio Craxì, Simona Marenco, C.F. Perno, Luciano Milanesi, V.C. Di Maio, and A. Mazzola
Subjects: chemistry.chemical_compound, Daclatasvir, Hepatology, chemistry, business.industry, Interferon, Kinetics, Asunaprevir, Medicine, Pharmacology, business, Early phase, medicine.drug
Published: 2015
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48. Natural HCV resistance is common in Italy and differently associated to genotypes

Author: Simona Landonio, Barbara Menzaghi, Giustino Parruti, T. Ruggiero, Valeria Cento, Francesca Ceccherini-Silberstein, Ilaria Lenci, M. Melis, Giuliano Rizzardini, Antonio Gasbarrini, P. Cacciatore, V. Pace Palitti, M.C. Sorbo, Ennio Polilli, Martina Milana, Alessandro Pieri, Laura Gianserra, Anna Claudia Pellicelli, P. Andreone, C. Masetti, Bianca Bruzzone, Simona Marenco, Elisabetta Teti, M. Andreoni, Gloria Taliani, Aldo Bertoli, Elisa Biliotti, Miriam Lichtner, Nicola Coppola, Vincenza Calvaruso, Fausto Baldanti, Stefania Paolucci, C.F. Perno, Carlo Magni, Sergio Babudieri, Valeria Micheli, Antonio Craxì, Filomena Morisco, V.C. Di Maio, Dante Romagnoli, Laura Ambra Nicolini, Mario Angelico, Loredana Sarmati, M. Siciliano, M. Puoti, N. Iapadre, Marianna Aragri, Vincenzo Vullo, Caterina Pasquazzi, and F. De Leonardis
Subjects: 0301 basic medicine, Genetics, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Hepatology, Resistance (ecology), business.industry, Genotype, Gastroenterology, Medicine, 030211 gastroenterology & hepatology, business
Published: 2017
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49. Gain of positively charged amino acids at specific positions of HBsAg C-terminus tightly correlates with HBV-induced hepatocellular carcinoma by altering the structural folding of this domain

Author: Luna Colagrossi, Giuseppina Cappiello, Hervé Fleury, N. Iapadre, Alberto Spanò, Aldo Bertoli, A. Ricciardi, Simona Francioso, C.F. Perno, Marianna Aragri, F. Ceccherini-Silberstein, V. Svicher, J. Vecchiet, R. Salpini, R. Longo, Giustino Parruti, Caterina Pasquazzi, Mario Angelico, L. Piermatteo, Lavinia Fabeni, A. Battisti, Pascale Trimoulet, Ilaria Lenci, T. Mari, A. Barlattani, L. Carioti, Domenico Di Carlo, S. Romano, L. Sarmati, and M. Andreoni
Subjects: chemistry.chemical_classification, Folding (chemistry), HBsAg, Hepatology, chemistry, Biochemistry, Hepatocellular carcinoma, C-terminus, Domain (ring theory), medicine, medicine.disease, Amino acid
Published: 2017
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50. P1235 BASELINE/EARLY PRESENCE OF KNOWN AND NOVEL RESISTANCE MUTATIONS IS ASSOCIATED WITH VIRAL FAILURE IN DIFFICULT-TO-TREAT PATIENTS TREATED WITH FIRST GENERATION PROTEASE INHIBITORS

Author: C.F. Perno, Alessandro Gasbarrini, Marianna Aragri, J. Vecchiet, M. Andreoni, Carlo Magni, Ilaria Lenci, Valeria Cento, F.P. Antonucci, Daniele Armenia, Simona Landonio, Laura Ambra Nicolini, D. Di Paolo, M. Siciliano, M. Tontodonati, Giustino Parruti, Maria Concetta Bellocchi, Sergio Babudieri, Anna Claudia Pellicelli, Mario Angelico, Maria Stella Mura, Giuliano Rizzardini, Cesare Sarrecchia, F. De Leonardis, Gloria Taliani, F. Ceccherini-Silberstein, V.C. Di Maio, Alessandro Mancon, A. Di Biagio, Lorenzo Nosotti, Valeria Micheli, and A. Manunta
Subjects: Protease, Hepatology, business.industry, medicine.medical_treatment, medicine, Baseline (configuration management), business, Virology, First generation
Published: 2014
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