Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Hézode C. Treatment of hepatitis C: Results in real life. Liver Int 2018;38 Suppl 1:21-27. [PMID: 29427481 DOI: 10.1111/liv.13638] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 11/17/2017] [Indexed: 12/17/2022]

For:	Hézode C. Treatment of hepatitis C: Results in real life. Liver Int 2018;38 Suppl 1:21-27. [PMID: 29427481 DOI: 10.1111/liv.13638] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 11/17/2017] [Indexed: 12/17/2022]

Number

Cited by Other Article(s)

Cheema JS, Suckow S, Ramers C, Loose P, Tomada A, Tweeten S, Stamos-Buesig T, Abramovitz D, Eger WH, Strathdee SA, Martin NK. Is San Diego California on Track to Reach HCV Elimination? A Modeling Analysis of Combination Prevention Strategies. Viruses 2024;16:1819. [PMID: 39772129 PMCID: PMC11680419 DOI: 10.3390/v16121819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 11/05/2024] [Accepted: 11/08/2024] [Indexed: 01/11/2025] Open

Abstract

In 2020, the Eliminate Hepatitis C Initiative in the county of San Diego (COSD) was launched, a private-public joint endeavor between the COSD and the American Liver Foundation. We use epidemic modeling to assess whether the COSD is on track to reach its elimination targets (80% reduction in incidence, 65% reduction in hepatitis C virus (HCV)-related mortality by 2030 compared to 2015) and what intervention scale-up may be required. We adapted a previously developed dynamic, deterministic model of HCV transmission and disease progression among adults in the COSD, stratified by risk, age, gender, and human immunodeficiency virus (HIV) status. The model is calibrated to detailed historical epidemiological data on HCV burden, treatment, and mortality in the COSD. We project HCV infections and mortality under status quo HCV treatment (65%/year among people coinfected with HCV and HIV, 0-5%/year among others) and determine what treatment scale-up among those without HIV is required to achieve HCV elimination, with or without concomitant reductions in injection transmission risk from 2024 onward. We project an increase in new HCV infections in the COSD to 2213 [95% C.I.: 1069-3763] in 2030, a mean 91% relative increase between 2015 and 2030. HCV-related deaths are expected to decrease to 246 [95% C.I.: 180-295] in 2030, a mean relative decrease of 14% compared to 2015. The incidence elimination target could be achieved through increasing HCV treatment among those without HIV to a mean of 60%/year, similar to the level achieved among people coinfected with HCV and HIV. Combination interventions reduce the treatment needed; if injecting risk is reduced by 25%, then treating 48%/year could achieve elimination. The COSD is likely not on track to reach the incidence or mortality targets, but achieving the incidence target is possible if treatment rates overall are scaled-up to rates that have been achieved among people coinfected with HCV and HIV. Elimination is achievable but requires committed funding and expansion of comprehensive testing, linkage, and treatment programs alongside harm reduction initiatives.

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Raoufinia R, Arabnezhad A, Keyhanvar N, Abdyazdani N, Saburi E, Naseri N, Niazi F, Niazi F, Namdar AB, Rahimi HR. Leveraging stem cells to combat hepatitis: a comprehensive review of recent studies. Mol Biol Rep 2024;51:459. [PMID: 38551743 DOI: 10.1007/s11033-024-09391-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 02/27/2024] [Indexed: 04/02/2024]

Debette-Gratien M, François S, Chevalier C, Alain S, Carrier P, Rigaud C, Abraham B, Burgevin AL, Courat L, Debenes B, Koffi J, Caux-Nussbaum E, Zattoni-Leroy J, Feuillet-Sow G, Dumont Q, Nubukpo P, Loustaud-Ratti V. Towards hepatitis C elimination in France: Scanvir, an effective model to test and treat drug users on dedicated days. J Viral Hepat 2023;30:355-361. [PMID: 36597183 DOI: 10.1111/jvh.13798] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 12/22/2022] [Accepted: 12/28/2022] [Indexed: 01/05/2023]

Cheema JS, Mathews WC, Wynn A, Bamford LB, Torriani FJ, Hill LA, Rajagopal AV, Yin J, Jain S, Garfein RS, Cachay ER, Martin NK. Hepatitis C Virus Micro-elimination Among People With HIV in San Diego: Are We on Track? Open Forum Infect Dis 2023;10:ofad153. [PMID: 37065984 PMCID: PMC10099471 DOI: 10.1093/ofid/ofad153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 03/20/2023] [Indexed: 04/18/2023] Open

Fucosylated haptoglobin is a novel predictive marker of hepatocellular carcinoma after hepatitis C virus elimination in patients with advanced liver fibrosis. PLoS One 2022;17:e0279416. [PMID: 36542633 PMCID: PMC9770342 DOI: 10.1371/journal.pone.0279416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 12/06/2022] [Indexed: 12/24/2022] Open

Viral proteases as therapeutic targets. Mol Aspects Med 2022;88:101159. [PMID: 36459838 PMCID: PMC9706241 DOI: 10.1016/j.mam.2022.101159] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 11/21/2022] [Accepted: 11/23/2022] [Indexed: 11/30/2022]

Trifan A, Stratina E, Rotaru A, Stafie R, Zenovia S, Nastasa R, Huiban L, Sfarti C, Cojocariu C, Cuciureanu T, Muzica C, Chiriac S, Girleanu I, Singeap AM, Stanciu C. Changes in Liver Steatosis Using Controlled Attenuation Parameter among Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals Therapy Who Achieved Sustained Virological Response. Diagnostics (Basel) 2022;12:702. [PMID: 35328255 PMCID: PMC8947513 DOI: 10.3390/diagnostics12030702] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 02/06/2023] Open

Abstract

Chronic hepatitis C virus (HCV) infection induces hepatic steatosis due to viral and host factors. However, information regarding the effects of direct-acting antivirals (DAAs) therapy on liver steatosis and fibrosis is limited. Vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) represents a non-invasive method, which has been used in the last few years for the detection of hepatic steatosis and fibrosis before and at a sustained virological response at 12 weeks (SVR12). The aim of this study was to assess the modifications of liver steatosis and fibrosis in HCV-infected patients who achieved SVR12. Consecutive patients with chronic HCV infection that were treated with DAAs in a tertiary gastroenterology center from Romania were included. Demographics, laboratory data, and VCTE evaluation were recorded in all patients. Patients with previous hepatic decompensation and those who did not achieve SVR were excluded. Two hundred and eighty patients (67.1% females) who achieved SVR12 were included. Regarding the changes in biological parameters, including liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), reduced to normal levels at SVR12 compared to the baseline (28.72 ± 24.71 U/L vs. 40.72 ± 27.34 U/L for ALT, p < 0.013 and 27.21 ± 11.15 U/L vs. 33.35 ± 23.37 U/L for AST, p = 0.029). On the contrary, the levels of triglycerides increased significantly from the baseline to SVR12 (124.03 ± 113.49 mg/dL to 153.78 ± 94.53, p = 0.004). Regarding hepatic steatosis by CAP evaluation, at SVR12, 186 (66.4%) of the individuals had a CAP score of ≥248 dB/m, an increase of 4.6% from the baseline. After viral eradication with DAAs, we observed an increase in hepatic steatosis. Hence, a long-term follow-up is mandatory to identify HCV-infected patients with hepatic steatosis post-SVR and the risk factors for more severe outcomes.

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Affiliation(s)

Anca Trifan Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Ermina Stratina Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Adrian Rotaru Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Remus Stafie Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Sebastian Zenovia Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Robert Nastasa Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Laura Huiban Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Catalin Sfarti Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Camelia Cojocariu Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Tudor Cuciureanu Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Cristina Muzica Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Stefan Chiriac Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Irina Girleanu Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Ana-Maria Singeap Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
Carol Stanciu Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.) Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania

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Pabjan P, Brzdęk M, Chrapek M, Dziedzic K, Dobrowolska K, Paluch K, Garbat A, Błoniarczyk P, Reczko K, Stępień P, Zarębska-Michaluk D. Are There Still Difficult-to-Treat Patients with Chronic Hepatitis C in the Era of Direct-Acting Antivirals? Viruses 2022;14:96. [PMID: 35062302 PMCID: PMC8779728 DOI: 10.3390/v14010096] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 12/29/2021] [Accepted: 01/04/2022] [Indexed: 12/17/2022] Open

Feldman TC, Dienstag JL, Mandl KD, Tseng YJ. Machine-learning-based predictions of direct-acting antiviral therapy duration for patients with hepatitis C. Int J Med Inform 2021;154:104562. [PMID: 34482150 DOI: 10.1016/j.ijmedinf.2021.104562] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 08/15/2021] [Accepted: 08/16/2021] [Indexed: 02/09/2023]

Abstract

INTRODUCTION

Hepatitis C, which affects 71 million persons worldwide, is the most common blood-borne pathogen in the United States. Chronic infections can be treated effectively thanks to the availability of modern direct-acting antiviral (DAA) therapies. Real-world data on the duration of DAA therapy, which can be used to optimize and guide the course of therapy, may also be useful in determining quality of life enhancements based upon total required supply of medication and long-term improvements to quality of life. We developed a machine learning model to identify patient characteristics associated with prolonged DAA treatment duration.

METHODS

A nationwide U.S. commercial managed care plan with claims data that covers about 60 million beneficiaries from 2009 to 2019 were used in the retrospective study. We examined differences in age, gender, and multiple comorbidities among patients treated with different durations of DAA treatment. We also examined the performance of machine learning models for predicting a prolonged course of DAA based on the area under the receiver operating characteristic curve (AUC).

RESULTS

We identified 3943 cases with hepatitis C who received sofosbuvir/ledipasvir as the first course of DAA and were eligible for the study. Patients receiving prolonged treatment (n = 240, 6.1%) were more likely to have compensated cirrhosis, decompensated cirrhosis, and other comorbidities (P < 0.001). For distinguishing patients who received prolonged DAA treatment for hepatitis C from patients received standard treatment, the optimal predictive model, constructed with XGBoost, had an AUC of 0.745 ± 0.031 (P < 0.001).

CONCLUSIONS

The risk of antiviral resistance and the cost of DAA are strong motivators to ensure that first-round DAA therapy is effective. For the dominant DAA treatment during the course of this analysis, we present a model that identifies factors already captured in established guidelines and adds to those age, comorbidity burden, and type 2 diabetes status; patient characteristics that are predictive of extended treatment.

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In Vitro Comparison of the Internal Ribosomal Entry Site Activity from Rodent Hepacivirus and Pegivirus and Construction of Pseudoparticles. Adv Virol 2021;2021:5569844. [PMID: 34422054 PMCID: PMC8376455 DOI: 10.1155/2021/5569844] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 07/20/2021] [Indexed: 01/17/2023] Open

Macgregor L, Ward Z, Martin NK, Nicholls J, Desai M, Hickson F, Weatherburn P, Hickman M, Vickerman P. The cost-effectiveness of case-finding strategies for achieving hepatitis C elimination among men who have sex with men in the UK. J Viral Hepat 2021;28:897-908. [PMID: 33759257 PMCID: PMC9132016 DOI: 10.1111/jvh.13503] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 03/03/2021] [Indexed: 01/20/2023]

Aghemo A, Alberti A, Andreone P, Angelico M, Brunetto MR, Chessa L, Ciancio A, Craxì A, Gaeta GB, Galli M, Gasbarrini A, Giorgini A, Grilli E, Lampertico P, Lichtner M, Milella M, Morisco F, Persico M, Pirisi M, Puoti M, Raimondo G, Romano A, Russello M, Sangiovanni V, Schiavini M, Serviddio G, Villa E, Vinci M, De Michina A, Gallinaro V, Gualberti G, Roscini AS, Zignego AL. Effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients: Results of the Italian cohort of a post-marketing observational study. Dig Liver Dis 2021;53:612-619. [PMID: 32917546 DOI: 10.1016/j.dld.2020.08.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 08/05/2020] [Accepted: 08/07/2020] [Indexed: 12/11/2022]

Affiliation(s)

Alessio Aghemo Humanitas Clinical and Research Center IRCCS and Humanitas University
Alfredo Alberti Dipartimento di Medicina Molecolare Università di Padova, 35122 Padova, Italy
Pietro Andreone Dipartimento di Scienze Mediche, Materno Infantili e dell'Adulto, Università di Modena e Reggio Emilia, 41125 Modena, Italy
Mario Angelico Dipartimento di Medicina - UOC di Epatologia, Fondazione PTV - Policlinico Tor Vergata, 00133 Roma, Italy
Maurizia Rossana Brunetto Dipartimento di Medicina clinica e sperimentale Università di Pisa - UO Epatologia, Azienda Ospedaliero - Universitaria Pisana, 56126 Pisa, Italy
Luchino Chessa Liver Unit, University Hospital, Monserrato, 09042 Cagliari, Italy
Alessia Ciancio Dipartimento di Scienze Mediche, SC GastroEpatologia U, A.O.U. Città della Salute e della Scienza di Torino, Università di Medicina, 10126 Torino, Italy
Antonio Craxì Dipartimento Biomedico di Medicina Interna e Specialistica - Reparto di Gastroenterologia, Azienda Ospedaliera Universitaria Policlinico P. Giaccone, 90127 Palermo, Italy
Giovanni Battista Gaeta Dipartimento Salute Mentale e Fisica, UOC Malattie Infettive, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Napoli, Italy
Massimo Galli Dip. Scienze Biomediche e Cliniche L. Sacco - UNIMI, III Divisione Malattie Infettive, ASST Fatebenefratelli Sacco, 20131 Milano, Italy
Antonio Gasbarrini UOC Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00136 Roma, Italy
Alessia Giorgini Dipartimento di Malattie Epatologiche, Gastroenterologiche e Metaboliche, Reparto U.O di Epatologia e Gastroenterologia, ASST Santi Paolo e Carlo, 20142 Milano, Italy
Elisabetta Grilli Dipartimento Clinico UOC Immunodeficienze Virali, INMI Lazzaro Spallanzani IRCCS, 00149 Roma, Italy
Pietro Lampertico CRC "A. M. and A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, 20122 Milan, Italy
Miriam Lichtner Department of Public Health and Infectious Disease, Sapienza University of Rome, Polo Pontino, SM Goretti Hospital, 04100 Latina, Italy
Michele Milella DIMO - U.O.C. di Malattie Infettive, Azienda Universitaria Ospedaliera Consorziale-Policlinico Bari, 70124 Bari, Italy
Filomena Morisco Dipartimento di Medicina Clinica e Chirurgica, UOC di Gastroenterologia ed Epatologia, Università Federico II, 80138 Napoli, Italy
Marcello Persico Dipartimento di Medicina Clinica Medica, Epatologica e Lungodegenza, AOU OO. RR. San Giovanni di Dio Ruggi e D'Aragona, 84131 Salerno, Italy
Mario Pirisi Università del Piemonte Orientale, Dipartimento di Medicina Traslazionale, 28100 Novara, Italy
Massimo Puoti Dipartimento Medico Polispecialistico - SC Malattie Infettive - ASST Grande Ospedale Metropolitano Niguarda, 20162 Milano, Italy
Giovanni Raimondo Dipartimento di Medicina Clinica e Sperimentale, UOC di Epatologia Clinica e Biomolecolare, Università ed AOU di Messina, 98125 Messina, Italy
Antonietta Romano Dipartimento di Medicina (DIMED) UOC Clinica Medica 5, A. O. Di Padova, 35128 Padova, Italy
Maurizio Russello Dipartimento Medicina Interna, UOSD Epatologia, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi - Presidio Ospedaliero Garibaldi-Nesima, 95122 Catania, Italy
Vincenzo Sangiovanni UOC III Divisione Ospedale Cotugno, 80131 Napoli, Italy
Monica Schiavini 1° Divisione di Malattie Infettive, ASST-FBF- Sacco, 20131 Milano, Italy
Gaetano Serviddio Unità Universitaria di Epatologia, OORR Ospedali Riuniti - Università degli Studi di Foggia, 71122 Foggia, Italy
Erica Villa UC Gastroenterologia, Dipartimento di Specialità Mediche, Azienda Ospedaliera Universitaria di Modena, 41125 Modena, Italy
Maria Vinci Dipartimento Medico Polispecialistico, S.C. Epatologia e Gastroenterologia, ASST Grande Ospadale Metropolitano Niguarda, 20162 Milano, Italy
Antonella De Michina Medical Department, AbbVie S.r.l., 00144 Roma, Italy
Valentina Gallinaro Medical Department, AbbVie S.r.l., 00144 Roma, Italy
Giuliana Gualberti Medical Department, AbbVie S.r.l., 00144 Roma, Italy
Antonio Saverio Roscini Medical Department, AbbVie S.r.l., 00144 Roma, Italy
Anna Linda Zignego Dipartimento di Medicina Sperimentale e Clinica, Centro Interdipartimentale di Epatologia Università di Firenze e C.R.I.A. MASVE AOU Careggi, Firenze, Italy.

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Bove G, Mehnert AK, Dao Thi VL. iPSCs for modeling hepatotropic pathogen infections. IPSCS FOR STUDYING INFECTIOUS DISEASES 2021:149-213. [DOI: 10.1016/b978-0-12-823808-0.00013-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]

Sacco R, Messina V, Gentilucci UV, Adinolfi LE, Ascione A, Barbarini G, Barlattani A, Cariti G, Cozzolongo R, Fimiani B, Francavilla R, Furlan C, Garrucciu G, Iovinella V, Rinaldi L, Marignani M, Begini P, Palitti VP, Pellicelli AM, Scifo G, Facciorusso A, Giacomelli L, Shah A, Bertino G, Perazzo S, Bresci G, Izzi A. Sustained virological response in patients with HCV treated with daclatasvir plus sofosbuvir, with or without ribavirin: a large, field-practice study. Drugs Context 2020;9:dic-2020-4-11. [PMID: 33408749 PMCID: PMC7747789 DOI: 10.7573/dic.2020-4-11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 11/03/2020] [Accepted: 11/14/2020] [Indexed: 11/21/2022] Open

Affiliation(s)

Rodolfo Sacco Gastroenterology and Metabolic Diseases Unit - Pisa University Hospital, Pisa, Italy
Vincenzo Messina Infectious Disease Unit Sant'Anna e San Sebastiano Hospital Caserta, Italy
Umberto Vespasiani Gentilucci Internal Medicine Unit Policlinico Campus Biomedico Rome, Italy
Luigi Elio Adinolfi Internal Medicine Unit "L Vanvitelli" University, Naples, Italy
Antonio Ascione Center for Liver Diseases "Buon Consiglio-Fatebenefratelli" Hospital, Naples, Italy
Giorgio Barbarini Infectious Diseases Unit IRCCS San Matteo, Pavia, Italy
Angelo Barlattani Center for Liver Diseases, Rome, Italy
Giuseppe Cariti Unit of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Turin, Italy
Raffaele Cozzolongo Division of Gastroenterology, IRCCS "S De Bellis Hospital", Castellana Grotte, Italy
Basilio Fimiani Internal Medicine Unit, "Umberto I" Hospital, Nocera Inferiore, Italy
Ruggiero Francavilla Center for Liver Diseases Bisceglie, Italy
Caterina Furlan Infectious and Tropical Diseases Policlinico "Umberto I", Rome, Italy
Giovanni Garrucciu Medical Pathology Unit University of Sassari Sassari, Italy
Vincenzo Iovinella Internal Medicine Unit "San Paolo" Hospital Naples, Italy
Luca Rinaldi Internal Medicine Unit "L Vanvitelli" University, Naples, Italy
Massimo Marignani Digestive and Liver Diseases "S. Andrea" Hospital Rome, Italy
Paola Begini Digestive and Liver Diseases "S. Andrea" Hospital Rome, Italy
Valeria Pace Palitti Hepatology Department of Medicine ASL Pescara, Pescara, Italy
Adriano M Pellicelli Liver Disease unit Department of Liver Transplantation "San Camillo" Hospital Rome, Italy
Gaetano Scifo Infectious Disease Unit "Umberto I" Hospital, Siracusa, Italy
Antonio Facciorusso Ospedali Riuniti di Foggia, Foggia, Italy
Luca Giacomelli Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
Aashni Shah Polistudium srl, Milan, Italy
Gaetano Bertino Hepatology Unit, Catania University, Italy
Serena Perazzo Department of Infectious Diseases and Emergency Infectious Diseases "D. Cotugno" Hospital Naples, Italy
Giampaolo Bresci Gastroenterology and Metabolic Diseases Unit - Pisa University Hospital, Pisa, Italy
Antonio Izzi Department of Infectious Diseases and Emergency Infectious Diseases "D. Cotugno" Hospital Naples, Italy

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Bahadur Gurung A, Ajmal Ali M, Lee J, Abul Farah M, Mashay Al-Anazi K. Structure-based virtual screening of phytochemicals and repurposing of FDA approved antiviral drugs unravels lead molecules as potential inhibitors of coronavirus 3C-like protease enzyme. JOURNAL OF KING SAUD UNIVERSITY. SCIENCE 2020;32:2845-2853. [PMID: 32837113 PMCID: PMC7366079 DOI: 10.1016/j.jksus.2020.07.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 06/09/2020] [Accepted: 07/12/2020] [Indexed: 05/10/2023]

Abstract

Coronaviruses are enveloped positive-strand RNA viruses belonging to family Coronaviridae and order Nidovirales which cause infections in birds and mammals. Among the human coronaviruses, highly pathogenic ones are Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV) which have been implicated in severe respiratory syndrome in humans. There are no approved antiviral drugs or vaccines for the treatment of human CoV infection to date. The recent outbreak of new coronavirus pandemic, coronavirus disease 2019 (COVID-19) has caused a high mortality rate and infections around the world which necessitates the need for the discovery of novel anti-coronaviral drugs. Among the coronaviruses proteins, 3C-like protease (3CLpro) is an important drug target against coronaviral infection as the auto-cleavage process catalysed by the enzyme is crucial for viral maturation and replication. The present work is aimed at the identification of suitable lead molecules for the inhibition of 3CLpro enzyme via a computational screening of the Food and Drug Administration (FDA) approved antiviral drugs and phytochemicals. Based on binding energies and molecular interaction studies, we shortlisted five lead molecules (both FDA approved drugs and phytochemicals) for each enzyme targets (SARS-CoV-2 3CLpro, SARS-CoV 3CLpro and MERS-CoV 3CLpro). The lead molecules showed higher binding affinity compared to the standard inhibitors and exhibited favourable hydrophobic interactions and a good number of hydrogen bonds with their respective targets. A few promising leads with dual inhibition potential were identified among FDA approved antiviral drugs which include DB13879 (Glecaprevir), DB09102 (Daclatasvir), molecule DB09297 (Paritaprevir) and DB01072 (Atazanavir). Among the phytochemicals, 11,646,359 (Vincapusine), 120,716 (Alloyohimbine) and 10,308,017 (Gummadiol) showed triple inhibition potential against all the three targets and 102,004,710 (18-Hydroxy-3-epi-alpha-yohimbine) exhibited dual inhibition potential. Hence, the proposed lead molecules from our findings can be further investigated through in vitro and in vivo studies to develop into potential drug candidates against human coronaviral infections.

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Su W, Tai Y, Tang SH, Ye YT, Zhao C, Gao JH, Tuo BG, Tang CW. Celecoxib attenuates hepatocyte apoptosis by inhibiting endoplasmic reticulum stress in thioacetamide-induced cirrhotic rats. World J Gastroenterol 2020;26:4094-4107. [PMID: 32821072 PMCID: PMC7403803 DOI: 10.3748/wjg.v26.i28.4094] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 05/21/2020] [Accepted: 06/25/2020] [Indexed: 02/06/2023] Open

Abstract

BACKGROUND

Endoplasmic reticulum (ER) stress is an important mechanism in the progression of chronic and acute liver diseases, especially in the progression and recovery of liver fibrosis. Excessive and long-term ER stress induces apoptosis. ER stress-induced apoptosis is considered to be an important pathway in the development of liver fibrosis. Cyclooxygenase-2 (COX-2) induction is also closely related to ER stress. In our previous studies, we showed that celecoxib, a COX-2 inhibitor, improves liver fibrosis and portal hypertension. However, the role and mechanism of celecoxib in alleviating liver fibrosis remain unclear.

AIM

To investigate whether celecoxib alleviates liver fibrosis by inhibiting hepatocyte apoptosis via the ER stress response.

METHODS

Cirrhosis was induced by intraperitoneal injections of thioacetamide (TAA) for 16 wk (injection dose is 200 mg/kg per 3 d for the first 8 wk and 100 mg /kg per 3 d after 8 wk). Thirty-six male Sprague-Dawley rats were randomly divided into three groups, namely, control group, TAA group, and TAA + celecoxib group. In the last 8 wk, TAA-induced cirrhotic rats received celecoxib (20 mg/kg/day) or the vehicle by gastric gavage. After 16 wk, the rats were sacrificed, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) were detected. The hepatic fibrosis areas were evaluated by Sirius red staining and the degree of fibrosis was assessed by measuring the level of hydroxyproline. ER stress levels were evaluated by detecting the marker proteins glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), PKR-like ER protein kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 alpha (IRE1α). Apoptosis levels were evaluated by detecting caspase-12 and caspase-3.

RESULTS

The serum ALT and AST levels in the liver were significantly reduced by celecoxib; however, the serum ALB had no significant changes. Celecoxib significantly reduced the degree of liver fibrosis and the levels of hydroxyproline (-38% and -25.7%, respectively, P < 0.01). Celecoxib ameliorated ER stress by reducing the level of GRP78 compared to the TAA group (P < 0.05). Consistently, after celecoxib administration, the upregulation of TAA-induced hepatic apoptosis markers (caspase-12 and caspase-3) and CHOP were significantly inhibited. In addition, after celecoxib treatment, the expression of key molecules associated with ER stress (PERK, ATF6, and IRE1) was decreased (P < 0.05).

CONCLUSION

Therapeutic administration of celecoxib effectively reduces hepatic apoptosis in TAA-induced cirrhotic rats. The mechanism of action may be attributed to the suppression of CHOP expression, which subsequently inhibits ER stress.

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Schwambach KH, Farias MR, Neto GB, Blatt CR. Cost and Effectiveness of the Treatment of Chronic Hepatitis C in Brazil: Real-World Data. Value Health Reg Issues 2020;23:49-54. [PMID: 32702649 DOI: 10.1016/j.vhri.2020.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 03/09/2020] [Accepted: 05/11/2020] [Indexed: 11/30/2022]

Tran AN, Lim JK. Hepatitis C: How Good Are Real-Life Data and Do Generics Work. Gastroenterol Clin North Am 2020;49:279-299. [PMID: 32389363 DOI: 10.1016/j.gtc.2020.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]

Gozlan Y, Bucris E, Shirazi R, Rakovsky A, Ben-Ari Z, Davidov Y, Veizman E, Saadi T, Braun M, Cohen-Naftaly M, Shlomai A, Shibolet O, Zigmond E, Katchman H, Menachem Y, Safadi R, Galun E, Zuckerman E, Nimer A, Hazzan R, Maor Y, Saif AM, Etzion O, Lurie Y, Mendelson E, Mor O. High frequency of multiclass HCV resistance-associated mutations in patients failing direct-acting antivirals: real-life data. Antivir Ther 2020;24:221-228. [PMID: 30880684 DOI: 10.3851/imp3301] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/20/2019] [Indexed: 02/07/2023]

Abstract

BACKGROUND

Direct-acting antiviral (DAA) therapy has dramatically increased sustained virological response rates in HCV-infected patients. However, resistance-associated substitutions (RAS) interfering with NS3- and NS5A-targeted therapy, still emerge. This real-life study analysed the type and frequency of RAS in rare cases of patients failing DAA regimens in 12 clinical centres in Israel.

METHODS

Blood samples and clinical data from 49 patients who failed various DAAs were collected. RAS identified in the NS3 and NS5A regions by population (Sanger) and next-generation sequencing (NGS) were compared by treatment regimen and HCV subtypes.

RESULTS

The majority (71.4%, 35/49) of patients were infected with the genotype (GT)1b strain, while 12.2% (6/49) carried GT1a and 14.3% GT3a/b (7), GT4a (1) and GT1b/GT3a. RAS were identified in 85.7% (42/49) of failures, of which 90.5% (38/42) were clinically relevant RAS (known to be associated with a specific GT and DAA in patients failing therapy or those with more than twofold change in in vitro replicon assays). The most abundant RAS were 168A/E/Q/G/N/V (32.6%, 16/49) identified in NS3, and 93H/N (61.2%, 30/49), 31I/M/V (34.7%, 17/49) and 30R/H/K (12.2%, 6/49), identified in NS5A. Significantly more clinically relevant RAS were identified in NS5A (82.2%, 37/45) than in NS3 (35.7%, 10/28; P<0.01). While RAS were identified in all GT1a, GT3b and GT4a failures (100%, 10/10), only 71.8% (28/39) of GT1b or GT3a failures had RAS (P=0.09). In four cases, NGS identified additional clinically relevant RAS and in one patient, NGS deciphered coexistence of GT3a and GT1b infections.

CONCLUSIONS

Our findings, together with additional real-life data, will contribute to the optimization of retreatment in DAA failure, when cost-related and suboptimal regimens must be employed.

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Affiliation(s)

Yael Gozlan Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Ramat Gan, Israel
Efrat Bucris Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Ramat Gan, Israel
Rachel Shirazi Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Ramat Gan, Israel
Avia Rakovsky Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Ramat Gan, Israel
Ziv Ben-Ari Liver Disease Center, Sheba Medical Center, Ramat Gan, Israel.,The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Yana Davidov Liver Disease Center, Sheba Medical Center, Ramat Gan, Israel
Ella Veizman Liver Unit, Rambam Medical Center, Haifa, Israel
Tarek Saadi Liver Unit, Rambam Medical Center, Haifa, Israel
Marius Braun The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Liver Institute, Rabin Medical Center, Petah Tikva, Israel
Michal Cohen-Naftaly The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Liver Institute, Rabin Medical Center, Petah Tikva, Israel
Amir Shlomai The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Liver Institute, Rabin Medical Center, Petah Tikva, Israel
Oren Shibolet The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
Ehud Zigmond The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
Helena Katchman The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
Yoram Menachem The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
Rifaat Safadi Liver Unit, Carmel Medical Center, Haifa, Israel
Eitan Galun Liver Unit, Hadassah Medical Center, Jerusalem, Israel
Eli Zuckerman Liver Unit, Carmel Medical Center, Haifa, Israel
Assy Nimer Faculty of Medicine in the Galilee, Bar-Ilan University, Ramat Gan, Israel.,Internal Medicine Department, Galilee Medical Center, Nahariya, Israel
Rawi Hazzan Liver Unit, Haemek Medical Center, Afula, Israel
Yaakov Maor The Institute of Gastroenterology and Hepatology, Kaplan Medical Center, Rehovot, Israel.,The Hebrew University Faculty of Medicine, Jerusalem, Israel
Abu Moch Saif Liver Unit, Hillel Yaffe Medical Center, Hadera, Israel
Ohad Etzion Department of Gastroenterology & Liver Diseases, Soroka University Medical Center, Beer Sheva, Israel
Yoav Lurie Liver Unit, Shaare Zedek Medical Center, Jerusalem, Israel
Ella Mendelson Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Ramat Gan, Israel.,The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Orna Mor Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Ramat Gan, Israel.,The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

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Lazarus JV, Roel E, Elsharkawy AM. Hepatitis C Virus Epidemiology and the Impact of Interferon-Free Hepatitis C Virus Therapy. Cold Spring Harb Perspect Med 2020;10:cshperspect.a036913. [PMID: 31570385 DOI: 10.1101/cshperspect.a036913] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]

Cell Culture Studies of the Efficacy and Barrier to Resistance of Sofosbuvir-Velpatasvir and Glecaprevir-Pibrentasvir against Hepatitis C Virus Genotypes 2a, 2b, and 2c. Antimicrob Agents Chemother 2020;64:AAC.01888-19. [PMID: 31818814 DOI: 10.1128/aac.01888-19] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 11/26/2019] [Indexed: 12/14/2022] Open

Abstract

The introduction of highly efficient therapies with direct-acting antivirals (DAA) for patients with chronic hepatitis C virus (HCV) infection offers exceptional opportunities to globally control this deadly disease. For achieving this ambitious goal, it is essential to prevent antiviral resistance against the most optimal first-line and retreatment DAA choices. We performed independent comparisons of the efficacy and barrier to resistance of pangenotypic DAA regimens for HCV genotype 2 infections, using previously and newly developed efficient cell culture-adapted strains of subtypes 2a, 2b, and 2c. With the applied experimental cell culture conditions, combination treatment with the sofosbuvir-velpatasvir or glecaprevir-pibrentasvir DAA regimen was efficient in eradicating HCV infections; in contrast, single-drug treatments frequently led to viral escape. Sequence analysis of drug targets from recovered viruses revealed known resistance-associated substitutions (RAS) emerging in the NS3 protease or NS5A after treatment failure. These RAS were genetically stable after viral passage, and viruses with these RAS exhibited significant phenotypic resistance. After sofosbuvir treatment failure, only a genotype 2a virus harbored NS5B RAS S282T and thus had decreased susceptibility to nucleotide analogs (nucs). However, in most cases, viral escape from sofosbuvir led to other NS5B substitutions but drug susceptibility was maintained, and in one case, no changes in NS5B were detected. For a genotype 2b virus, after treatment failure with sofosbuvir-velpatasvir, the efficacy of retreatment with glecaprevir-pibrentasvir was maintained due to the high barrier to resistance and low cross-resistance of pibrentasvir. Our findings suggest the slight superiority of glecaprevir-pibrentasvir against genotype 2b in culture, which could have potential therapeutic interest meriting more definitive investigations in the clinic.

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Buonomo AR, Scotto R, Coppola C, Pinchera B, Viceconte G, Rapillo CM, Staiano L, Saturnino M, Scarano F, Portunato F, Pisaturo M, De Pascalis S, Martini S, Tosone G, Nappa S, Coppola N, Gentile I. Direct acting antivirals treatment for hepatitis C virus infection does not increase the incidence of de novo hepatocellular carcinoma occurrence: Results from an Italian real-life cohort (LINA cohort). Medicine (Baltimore) 2020;99:e18948. [PMID: 32028404 PMCID: PMC7015572 DOI: 10.1097/md.0000000000018948] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open

Affiliation(s)

Antonio Riccardo Buonomo Department of Clinical Medicine and Surgery – Section of Infectious Diseases, University of Naples Federico II
Riccardo Scotto Department of Clinical Medicine and Surgery – Section of Infectious Diseases, University of Naples Federico II
Carmine Coppola Department of Internal Medicine - Unit of Hepatology and Interventional Ultrasonography. OORR Area Stabiese, Plesso Nuovo Gragnano, Naples
Biagio Pinchera Department of Clinical Medicine and Surgery – Section of Infectious Diseases, University of Naples Federico II
Giulio Viceconte Department of Clinical Medicine and Surgery – Section of Infectious Diseases, University of Naples Federico II
Costanza Maria Rapillo Department of Clinical Medicine and Surgery – Section of Infectious Diseases, University of Naples Federico II
Laura Staiano Department of Internal Medicine - Unit of Hepatology and Interventional Ultrasonography. OORR Area Stabiese, Plesso Nuovo Gragnano, Naples
Mariarosaria Saturnino Department of Internal Medicine - Unit of Hepatology and Interventional Ultrasonography. OORR Area Stabiese, Plesso Nuovo Gragnano, Naples
Ferdinando Scarano Department of Internal Medicine - Unit of Hepatology and Interventional Ultrasonography. OORR Area Stabiese, Plesso Nuovo Gragnano, Naples
Federica Portunato Department of Mental Health and Public Medicine – Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Caserta, Italy
Mariantonietta Pisaturo Department of Mental Health and Public Medicine – Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Caserta, Italy
Stefania De Pascalis Department of Mental Health and Public Medicine – Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Caserta, Italy
Salvatore Martini Department of Mental Health and Public Medicine – Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Caserta, Italy
Grazia Tosone Department of Clinical Medicine and Surgery – Section of Infectious Diseases, University of Naples Federico II
Salvatore Nappa Department of Clinical Medicine and Surgery – Section of Infectious Diseases, University of Naples Federico II
Nicola Coppola Department of Mental Health and Public Medicine – Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Caserta, Italy
Ivan Gentile Department of Clinical Medicine and Surgery – Section of Infectious Diseases, University of Naples Federico II

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Macgregor L, Desai M, Martin NK, Nicholls J, Hickson F, Weatherburn P, Hickman M, Vickerman P. Scaling up screening and treatment for elimination of hepatitis C among men who have sex with men in the era of HIV pre-exposure prophylaxis. EClinicalMedicine 2020;19:100217. [PMID: 32140664 PMCID: PMC7046521 DOI: 10.1016/j.eclinm.2019.11.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 11/13/2019] [Accepted: 11/14/2019] [Indexed: 12/14/2022] Open

Abstract

BACKGROUND

Routine HIV pre-exposure prophylaxis (PrEP) and HIV care appointments provide opportunities for screening men who have sex with men (MSM) for hepatitis C virus infection (HCV). However, levels of screening required for achieving the WHO elimination target of reducing HCV incidence by 90% by 2030 among all MSM are unknown.

METHODS

An HCV/HIV transmission model was calibrated to UK prevalence of HIV among MSM (4·7%) and chronic HCV infection among HIV-positive MSM (9·9%) and HIV-negative MSM (1.2%). Assuming 12·5% coverage of PrEP among HIV-negative MSM, we evaluated the relative reduction in overall HCV incidence by 2030 (compared to 2018 levels) of HCV screening every 12/6-months (alongside completing direct acting antiviral treatment within 6-months of diagnosis) in PrEP users and/or HIV-diagnosed MSM. We estimated the additional screening required among HIV-negative non-PrEP users to reduce overall incidence by 90% by 2030. The effect of 50% reduction in condom use among PrEP users (risk compensation) was estimated.

RESULTS

Screening and treating PrEP users for HCV every 12 or 6-months decreases HCV incidence by 67·3% (uncertainty range 52·7-79·2%) or 70·2% (57·1-80·8%), respectively, increasing to 75·4% (59·0-88·6%) or 78·8% (63·9-90·4%) if HIV-diagnosed MSM are also screened at same frequencies. Risk compensation reduces these latter projections by <10%. To reduce HCV incidence by 90% by 2030 without risk compensation, HIV-negative non-PrEP users require screening every 5·6 (3·8-9·2) years if MSM on PrEP and HIV-diagnosed MSM are screened every 6-months, shortening to 4·4 (3·1-6·6) years with risk compensation. For 25·0% PrEP coverage, the HCV elimination target can be reached without screening HIV-negative MSM not on PrEP, irrespective of risk compensation.

INTERPRETATION

At low PrEP coverage, increased screening of all MSM is required to achieve the WHO HCV-elimination targets for MSM in the UK, whereas at higher PrEP coverage this is possible through just screening HIV-diagnosed MSM and PrEP users.

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Renal safety in 3264 HCV patients treated with DAA-based regimens: Results from a large Italian real-life study. Dig Liver Dis 2020;52:190-198. [PMID: 31813755 DOI: 10.1016/j.dld.2019.11.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 11/11/2019] [Accepted: 11/12/2019] [Indexed: 12/11/2022]

Zappulo E, Scotto R, Buonomo AR, Maraolo AE, Pinchera B, Gentile I. Efficacy and safety of a fixed dose combination tablet of asunaprevir + beclabuvir + daclatasvir for the treatment of Hepatitis C. Expert Opin Pharmacother 2020;21:261-273. [PMID: 31914336 DOI: 10.1080/14656566.2019.1697674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Abstract

Introduction: Hepatitis C virus (HCV) is estimated to infect approximately 70 million people worldwide. If left untreated, chronic infection can progress to cirrhosis, liver failure or hepatocellular carcinoma. The advent of new direct-acting antivirals (DAA) has revolutionized patients' chances of treatment and viral elimination. Currently, several DAA options are available on the market.Areas covered: This review focuses on the pharmacokinetics, efficacy, tolerability and safety profile of DCV-TRIO, a twice-daily fixed-dose combination of daclatasvir, asunaprevir and beclabuvir approved in Japan for the treatment of genotype 1 HCV infection.Expert opinion: The DCV-TRIO combination achieved good response rates in genotype 1 patients (SVR12 ≥ 95% in naïve subtype 1b), independently from IL28B genotype, cirrhotic status and prior interferon exposure. On the other hand, unsatisfying response rates were reported in DAA-experienced patients and the risk of RAS selection should not be underestimated. Moreover, DCV-TRIO lacks differentiation from its earlier-launched DAA rivals, presents an inconvenient twice-daily dosing schedule and is not recommended in patients with advanced liver and kidney disease. All these drawbacks considerably limit its effective commercial potential. However, it can be a therapeutic option against HCV in tailored approaches according to the needs of different markets across the world.Abbreviations AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ASV: asunaprevir; AUC: area under the curve; BCRP: Breast Cancer Resistance Protein; BCV: boceprevir; BID: bis in die; CI: confidence intervals; CLcr: creatinine clearance; DAA: direct acting antivirals; DCV: daclatasvir; EC50: Half maximal effective concentration; GT: genotype; HCV: Hepatitis C virus; IFN: Interferon; NHL: non-Hodgkin lymphoma; OATP: Organic anion transporting polypeptides; OR: odds ratio; P-gp: P-glycoprotein; PK: pharmacokinetics; QD: quo die; RAS: resistance-associated substitutions; SVR: sustained virological response; USD: Unites States dollar.

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Persico M, Aglitti A, Milella M, Coppola C, Messina V, Claar E, Gentile I, Sogari F, Pierri P, Surace LA, Morisco F, Tundo P, Brancaccio G, Serviddio G, Gatti P, Termite AP, Di Costanzo GG, Caroleo B, Cozzolongo R, Coppola N, Longo A, Fontanella L, Federico A, Rosato V, Terrenato I, Masarone M. Real-life glecaprevir/pibrentasvir in a large cohort of patients with hepatitis C virus infection: The MISTRAL study. Liver Int 2019;39:1852-1859. [PMID: 31175707 DOI: 10.1111/liv.14170] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 05/30/2019] [Accepted: 06/03/2019] [Indexed: 12/17/2022]

Affiliation(s)

Marcello Persico Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
Andrea Aglitti Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
Michele Milella Clinic of Infectious Diseases, University of Bari, Bari, Italy
Carmine Coppola Internal Medicine and Hepatology Unit, Hospital of Gragnano, Gragnano, Italy
Vincenzo Messina Infectious Diseases Unit, AORN Caserta, Caserta, Italy
Ernesto Claar Hepatology Unit, "Villa Betania" Evangelical Hospital, Naples, Italy
Ivan Gentile Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
Fernando Sogari Internal Medicine Unit, "S.S. Annunziata" Hospital, Taranto, Italy
Paola Pierri Infectious Diseases and Hepatology Unit, Cotugno Hospital, Naples, Italy
Lorenzo A Surace Traveler and Migration Medicine Center, ASP Catanzaro, Catanzaro, Italy
Filomena Morisco Department of Clinical Medicine and Surgery, Gastroenterology and Hepatology Unit, Federico II University, Naples, Italy
Paolo Tundo S. Caterina Novella Hospital, Galatina, Lecce, Italy
Giuseppina Brancaccio Infectious Diseases Unit, University of Campania "Luigi Vanvitelli", Napoli, Italy
Gaetano Serviddio CURE Center, University of Foggia, Foggia, Italy
Pietro Gatti Internal Medicine Unit, Ostuni, Bari, Italy
Antonio P Termite Internal Medicine Unit, Hospital of Castellaneta, Taranto, Italy
Giovan G Di Costanzo Hepatology Unit, AORN Cardarelli, Naples, Italy
Benedetto Caroleo Geriatrics Unit, Mater Domini" University, Catanzaro, Italy
Raffaele Cozzolongo S. de Bellis Hospital-IRCCS, Castellana Grotte, Italy
Nicola Coppola Infectious Diseases Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
Annamaria Longo Infectious Disease Unit, Perrino Hospital, Brindisi, Italy
Luca Fontanella Liver Diseases Unit, Fatebenefratelli Hospital, Naples, Italy
Alessandro Federico Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
Valerio Rosato Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy.,Hepatology Unit, "Villa Betania" Evangelical Hospital, Naples, Italy
Irene Terrenato Biostatistics-Scientific Direction, IRCCS Regina Elena National Cancer Institute, Rome, Italy
Mario Masarone Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy

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Lu M, Wu KH, Li J, Moorman AC, Spradling PR, Teshale EH, Boscarino JA, Daida YG, Schmidt MA, Rupp LB, Zhang T, Trudeau S, Gordon SC. Adjuvant ribavirin and longer direct-acting antiviral treatment duration improve sustained virological response among hepatitis C patients at risk of treatment failure. J Viral Hepat 2019;26:1210-1217. [PMID: 31197910 PMCID: PMC6764853 DOI: 10.1111/jvh.13162] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 05/06/2019] [Accepted: 05/15/2019] [Indexed: 12/13/2022]

Abstract

The role of ribavirin (RBV) in the era of direct-acting antivirals (DAA) is not clear, and DAA studies have been largely genotype- and regimen-specific. Using data from the Chronic Hepatitis Cohort Study, we evaluated the role of RBV and increased DAA treatment duration among patients with chronic hepatitis C (HCV) in routine clinical care. We performed multivariable analysis of data from 4133 patients receiving any of the following: sofosbuvir (SOF); daclatasvir + SOF; grazoprevir + elbasvir; paritaprevir/ritonavir + ombitasvir; simeprevir + SOF; and SOF + ledipasvir; SOF + velpatasvir ± voxilaprevir; and glecaprevir + pibrentasvir-all with/ without RBV. Inverse probability treatment weighting was used to adjust for treatment selection bias. Sustained virological response (SVR) was defined by undetectable HCV RNA 12 weeks after end of therapy. The overall SVR rate was 95%. Mean treatment duration was 12 ± 4.5 weeks. The final model included treatment duration and diabetes, as well as the interaction of RBV with previous treatment status (treatment naïve, interferon treatment failure [TF] or previous DAA TF), cirrhosis status, and HCV genotype (GT). Each one-month increment of treatment duration increased odds of SVR by 99% (aOR = 1.99). Diabetes, previous DAA TF, and decompensated cirrhosis significantly reduced odds of SVR. RBV significantly increased the likelihood of SVR among patients with decompensated cirrhosis (aOR = 5.05), previous DAA treatment failure (aOR = 5.43), and GT3 (aOR = 13.28). Among RBV-free regimens, patients with GT3 were less likely to achieve SVR than those with GT1 or 2 (aOR 0.07). Diabetes, decompensated cirrhosis, and prior DAA TF independently reduced the likelihood of SVR. Longer treatment duration increased likelihood of SVR. Conclusion: RBV increased likelihood of SVR among patients with GT3, previous DAA TF, or decompensated cirrhosis.

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Pérez AB, Chueca N, Macías J, Pineda JA, Salmerón J, Rivero-Juárez A, Hidalgo-Tenorio C, Espinosa MD, Téllez F, Von-Wichmann MÁ, Omar M, Santos J, Hernández-Quero J, Antón JJ, Collado A, Lozano AB, García-Deltoro M, Casado M, Pascasio JM, Selfa A, Rosales JM, De la Iglesia A, Arenas JI, García-Bujalance S, Ríos MJ, Bernal E, Martínez O, García-Herola A, Vélez M, Rincón P, García F. Prevalence of resistance associated substitutions and efficacy of baseline resistance-guided chronic hepatitis C treatment in Spain from the GEHEP-004 cohort. PLoS One 2019;14:e0221231. [PMID: 31469856 PMCID: PMC6716636 DOI: 10.1371/journal.pone.0221231] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Accepted: 08/01/2019] [Indexed: 12/11/2022] Open

Affiliation(s)

Ana Belén Pérez Clinical Microbiology Unit, University Hospital Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
Natalia Chueca Clinical Microbiology Unit, University Hospital San Cecilio, Instituto de Investigacion Ibs. Granada, Granada, Spain
Juan Macías Infectious Diseases Unit, University Hospital Nuestra Señora de Valme, Sevilla, Spain
Juan Antonio Pineda Infectious Diseases Unit, University Hospital Nuestra Señora de Valme, Sevilla, Spain
Javier Salmerón Hepatology Unit, University Hospital San Cecilio Granada, Instituto de Investigación Ibs. CIBERehd, Granada, Spain
Antonio Rivero-Juárez Infectious Diseases Unit, University Hospital Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Córdoba, Spain
Carmen Hidalgo-Tenorio Infectious Diseases Unit, University Hospital Virgen de las Nieves, Granada, Spain
María Dolores Espinosa Hepatology Unit, University Hospital Virgen de las Nieves, Granada, Spain
Francisco Téllez Infectious Diseases Unit, Hospital Puerto Real, Puerto Real, Cádiz, Spain
Miguel Ángel Von-Wichmann Infectious Diseases Unit, University Hospital Donostia, San Sebastián, Spain
Mohamed Omar Infectious Diseases Unit, Complejo Hospitalario de Jaén, Jáen, Spain
Jesús Santos Infectious Diseases Unit, University Hospital Virgen de la Victoria, Málaga, Spain
José Hernández-Quero Infectious Diseases Unit, University Hospital San Cecilio, Granada, Spain
José Joaquin Antón Penitenciary Physician, Albolote Penitenciary, Albolote, Granada, Spain
Antonio Collado Infectious Diseases Unit, Complejo Hospitalario Torrecárdenas, Almería, Spain
Ana Belén Lozano Infectious Diseases Unit, Hospital de Poniente, El Ejido, Almería, Spain
Miguel García-Deltoro Infectious Diseases Unit, Hospital General de Valencia, Valencia, Spain
Marta Casado Hepatology Unit, Complejo Hospitalario Torrecárdenas, Almería, Spain
Juan Manuel Pascasio Hepatology Unit, University Hospital Virgen del Rocío, Seville, Spain
Aida Selfa Hepatology Unit, Hospital Comarcal Santa Ana, Motril Granada, Spain
José Miguel Rosales Hepatology Unit, Hospital Costa del Sol, Marbella, Málaga, Spain
Alberto De la Iglesia Clinical Microbiology Unit, University Hospital Infanta Elena, Huelva, Spain
Juan Ignacio Arenas Hepatology Unit, University Hospital Donostia, San Sebastián, Spain
Silvia García-Bujalance Clinical Microbiology Unit, University Hospital La Paz, Madrid, Spain
María José Ríos Infectious Diseases Unit, University Hospital Virgen Macarena, Seville, Spain
Enrique Bernal Infectious Diseases Unit, Hospital General Reina Sofía, Murcia, Spain
Onofre Martínez Infectious Diseases Unit, University Hospital Santa Lucía, Cartagena, Spain
Antonio García-Herola Hepatology Unit, Hospital Marina Baixa, Vilajoyosa, Alicante, Spain
Mónica Vélez Infectious Diseases Unit, Hospital General de La Palma, La Palma, Spain
Pilar Rincón Infectious Diseases Unit, University Hospital Nuestra Señora de Valme, Sevilla, Spain
Federico García Clinical Microbiology Unit, University Hospital San Cecilio, Instituto de Investigacion Ibs. Granada, Granada, Spain

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Back D, Belperio P, Bondin M, Negro F, Talal AH, Park C, Zhang Z, Pinsky B, Crown E, Mensa FJ, Marra F. Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV infection and psychiatric disorders: An integrated analysis. J Viral Hepat 2019;26:951-960. [PMID: 30977945 PMCID: PMC6852431 DOI: 10.1111/jvh.13110] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 01/13/2019] [Accepted: 02/11/2019] [Indexed: 12/25/2022]

Abstract

Although direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection are highly efficacious and safe, treatment initiation is often limited in patients with neuropsychiatric disorders due to concerns over reduced treatment adherence and drug-drug interactions. Here, we report adherence, efficacy, safety and patient-reported outcomes (PROs) from an integrated analysis of registrational studies using the pangenotypic DAA regimen of glecaprevir and pibrentasvir (G/P). Patients with chronic HCV genotypes 1-6 infection with compensated liver disease (with or without cirrhosis) receiving G/P for 8, 12 or 16 weeks were included in this analysis. Patients were classified as having a psychiatric disorder based on medical history and/or co-medications. Primary analyses assessed treatment adherence, efficacy (sustained virologic response at post-treatment week 12; SVR12), safety and PROs. Among 2522 patients receiving G/P, 789 (31%) had a psychiatric disorder with the most common diagnoses being depression (64%; 506/789) and anxiety disorders (27%; 216/789). Treatment adherence was comparably high (>95%) in patients with and without psychiatric disorders. SVR12 rates were 97.3% (768/789; 95% CI = 96.2-98.5) and 97.5% (1689/1733; 95% CI = 96.7-98.2) in patients with and without psychiatric disorders, respectively. Among patients with psychiatric disorders, SVR12 rates remained >96% by individual psychiatric diagnoses and co-medication classes. Overall, most adverse events (AEs) were mild-to-moderate in severity with serious AEs and AEs leading to G/P discontinuation occurring at similarly low rates in both patient populations. In conclusion, G/P treatment was highly efficacious, well-tolerated and demonstrated high adherence rates in patients with chronic HCV infection and psychiatric disorders.

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Søholm J, Holm DK, Mössner B, Madsen LW, Hansen JF, Weis N, Sauer AP, Awad T, Christensen PB. Incidence, prevalence and risk factors for hepatitis C in Danish prisons. PLoS One 2019;14:e0220297. [PMID: 31348813 PMCID: PMC6660074 DOI: 10.1371/journal.pone.0220297] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 07/12/2019] [Indexed: 12/17/2022] Open

What is killing people with hepatitis C virus infection? Analysis of a population-based cohort in Canada. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2019;72:114-122. [PMID: 31229445 DOI: 10.1016/j.drugpo.2019.06.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 05/23/2019] [Accepted: 06/06/2019] [Indexed: 12/14/2022]

Casado JL, Monsalvo M, Fontecha M, Vizcarra P, Rodriguez MA, Vivancos MJ, Moreno S. Dolutegravir plus rilpivirine as dual regimen in virologically suppressed HIV-1 infected patients in a clinical setting. HIV Res Clin Pract 2019;20:64-72. [PMID: 31303142 DOI: 10.1080/15284336.2019.1628460] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]

Telatin V, Nicoli F, Frasson C, Menegotto N, Barbaro F, Castelli E, Erne E, Palù G, Caputo A. In Chronic Hepatitis C Infection, Myeloid-Derived Suppressor Cell Accumulation and T Cell Dysfunctions Revert Partially and Late After Successful Direct-Acting Antiviral Treatment. Front Cell Infect Microbiol 2019;9:190. [PMID: 31259160 PMCID: PMC6588015 DOI: 10.3389/fcimb.2019.00190] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 05/17/2019] [Indexed: 12/16/2022] Open

Loo N, Hanysak B, Mann J, Ramirez R, Kim J, Mitchell R, Van Frank T, Guerrero R, Hinojosa K, Christensen K, Pedicone LD, Alkhouri N, Wells J, Landaverde C, Rodas F, Lawitz E, Poordad F. Real-world observational experience with direct-acting antivirals for hepatitis C: baseline resistance, efficacy, and need for long-term surveillance. Medicine (Baltimore) 2019;98:e16254. [PMID: 31261592 PMCID: PMC6617322 DOI: 10.1097/md.0000000000016254] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 05/04/2019] [Accepted: 06/06/2019] [Indexed: 12/13/2022] Open

Musialik J, Kolonko A, Kwiecień K, Owczarek AJ, Więcek A. Effectiveness and safety of sofosbuvir-based therapy against chronic hepatitis C infection after successful kidney transplantation. Transpl Infect Dis 2019;21:e13090. [PMID: 30972854 DOI: 10.1111/tid.13090] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 03/15/2019] [Accepted: 03/31/2019] [Indexed: 12/20/2022]

Lee YC, Hu TH, Hung CH, Lu SN, Chen CH, Wang JH. The change in liver stiffness, controlled attenuation parameter and fibrosis-4 index for chronic hepatitis C patients with direct-acting antivirals. PLoS One 2019;14:e0214323. [PMID: 30939158 PMCID: PMC6445421 DOI: 10.1371/journal.pone.0214323] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 03/10/2019] [Indexed: 12/17/2022] Open

Raja R, Pareek A, Newar K, Dixit NM. Mutational pathway maps and founder effects define the within-host spectrum of hepatitis C virus mutants resistant to drugs. PLoS Pathog 2019;15:e1007701. [PMID: 30934020 PMCID: PMC6459561 DOI: 10.1371/journal.ppat.1007701] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 04/11/2019] [Accepted: 03/13/2019] [Indexed: 12/11/2022] Open

Berg T, Naumann U, Stoehr A, Sick C, John C, Teuber G, Schiffelholz W, Mauss S, Lohmann K, König B, Pangerl A, Niederau C. Real-world effectiveness and safety of glecaprevir/pibrentasvir for the treatment of chronic hepatitis C infection: data from the German Hepatitis C-Registry. Aliment Pharmacol Ther 2019;49:1052-1059. [PMID: 30874328 DOI: 10.1111/apt.15222] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 12/30/2018] [Accepted: 02/18/2019] [Indexed: 12/11/2022]

Abstract

BACKGROUND

Glecaprevir/pibrentasvir is a pangenotypic direct-acting antiviral regimen approved for treating adults chronically infected with hepatitis C virus (HCV). There are limited real-world data on glecaprevir/pibrentasvir to date.

AIM

To evaluate the effectiveness and safety of glecaprevir/pibrentasvir under real-world conditions in the German Hepatitis C-Registry (DHC-R).

METHODS

The DHC-R is an ongoing, non-interventional, multicentre, prospective, observational cohort study that monitors patients with chronic HCV infection. Data were collected from patients who initiated glecaprevir/pibrentasvir and completed a screening visit on or after 2 August 2017. The primary effectiveness endpoint was sustained virological response at post-treatment Week 12 (SVR12). Safety and tolerability were also assessed.

RESULTS

As of 15 July 2018, 586 patients received glecaprevir/pibrentasvir and had documented SVR12 data, treatment discontinuation, loss to follow-up or HCV reinfection. Five hundred and fifty-two patients (94%) received on-label treatment. At baseline, most on-label patients were infected with HCV genotype 1 (53%) or 3 (33%), HCV treatment-naïve (90%), without cirrhosis (94%), and treated for 8 weeks (93%). Five hundred and thirty-four patients (96.7%) achieved SVR12 (intention-to-treat [ITT] analysis). By modified ITT analysis (excluding patients who discontinued and did not achieve SVR12 or patients lost to follow-up), the SVR12 rate was 99.4% (n/N = 534/537). There was one documented virological failure (relapse) and two documented HCV reinfections. One hundred and forty-two (26%) adverse events (AEs) and 9 (2%) serious AEs occurred; 2 (<1%) AEs led to treatment discontinuation. All patients treated off-label (N = 34) achieved SVR12.

CONCLUSION

Glecaprevir/pibrentasvir was highly effective and well tolerated under real-world conditions. Clinical trial number: DRKS00009717 (German Clinical Trials Register, DRKS).

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Besheer T, Elalfy H, Abd El-Maksoud M, Abd El-Razek A, Taman S, Zalata K, Elkashef W, Zaghloul H, Elshahawy H, Raafat D, Elemshaty W, Elsayed E, El-Gilany AH, El-Bendary M. Diffusion-weighted magnetic resonance imaging and micro-RNA in the diagnosis of hepatic fibrosis in chronic hepatitis C virus. World J Gastroenterol 2019;25:1366-1377. [PMID: 30918429 PMCID: PMC6429339 DOI: 10.3748/wjg.v25.i11.1366] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Revised: 01/30/2019] [Accepted: 02/16/2019] [Indexed: 02/06/2023] Open

Abstract

BACKGROUND

Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantiﬁcation of hepatic ﬁbrosis. In addition, the liver has numerous endogenous micro-RNAs (miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.

AIM

To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.

METHODS

This prospective study included 208 patients and 82 age- and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.

RESULTS

The ADC value decreased significantly with the progression of fibrosis, from controls (F0) to patients with early fibrosis (F1 and F2) to those with late fibrosis (F3 and F4) (median 1.92, 1.53, and 1.25 × 10^-3 mm²/s, respectively) (P = 0.001). The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^-3 mm²/s with an area under the curve (AUC) of 0.992. Combining ADC and miR-200b revealed the highest AUC (0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^-3 mm²/s with an AUC of 0.866. The combination of ADC and miR-200b revealed the best AUC (0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200b (r = - 0.61, P = 0.001), miR-21 (r = - 0.62, P = 0.001), and miR-29 (r = 0.52, P = 0.001).

CONCLUSION

Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.

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Rossi C, Young J, Martel-Laferrière V, Walmsley S, Cooper C, Wong A, Gill MJ, Klein MB. Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV-Coinfected Patients in Clinical Care. Open Forum Infect Dis 2019;6:ofz055. [PMID: 30882016 PMCID: PMC6411211 DOI: 10.1093/ofid/ofz055] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 01/24/2019] [Accepted: 02/12/2019] [Indexed: 12/27/2022] Open

Abstract

Background

There are limited data on the real-world effectiveness of direct-acting antiviral (DAA) treatment in patients coinfected with hepatitis C virus (HCV) and HIV—a population with complex challenges including ongoing substance use, cirrhosis, and other comorbidities. We assessed how patient characteristics and the appropriateness of HCV regimen selection according to guidelines affect treatment outcomes in coinfected patients.

Methods

We included all patients who initiated DAA treatment between November 2013 and July 2017 in the Canadian Co-Infection Cohort. Sustained virologic response (SVR) was defined as an undetectable HCV RNA measured between 10 and 18 weeks post-treatment. We defined treatment failure as virologic failure, relapse, or death without achieving SVR. Bayesian logistic regression was used to estimate the posterior odds ratios (ORs) associated with patient demographic, clinical, and treatment-related risk factors for treatment failure.

Results

Two hundred ninety-five patients initiated DAAs; 31% were treatment-experienced, 29% cirrhotic, and 80% HCV genotype 1. Overall, 92% achieved SVR (263 of 286, 9 unknown), with the highest rates in females (97%) and lowest in cirrhotics (88%) and high-frequency injection drug users (89%). Many patients (38%) were prescribed regimens that were outside current clinical guidelines. This did not appreciably increase the risk of treatment failure—particularly in patients with genotype 1 (prior odds ratio [OR], 1.5; 95% credible interval [CrI], 0.38–6.0; posterior OR, 1.0; 95% CrI, 0.40–2.5).

Conclusions

DAAs were more effective than anticipated in a diverse, real-world coinfected cohort, despite the use of off-label, less efficacious regimens. High-frequency injection drug use and cirrhosis were associated with an increased risk of failure.

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Lohmann V. Hepatitis C virus cell culture models: an encomium on basic research paving the road to therapy development. Med Microbiol Immunol 2019;208:3-24. [PMID: 30298360 DOI: 10.1007/s00430-018-0566-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 10/01/2018] [Indexed: 12/17/2022]

Health-related quality of life in hepatitis C patients who achieve sustained virological response to direct-acting antivirals: a comparison with the general population. Qual Life Res 2019;28:1477-1484. [PMID: 30666549 DOI: 10.1007/s11136-019-02111-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/11/2019] [Indexed: 12/18/2022]

Lazarus JV, Pericàs JM, Elsharkawy AM. Leaving behind pegylated interferon-based regimens to eliminate hepatitis C as a public health threat by 2030 as set out by WHO. Liver Int 2018;38:1902-1905. [PMID: 30358061 DOI: 10.1111/liv.13944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]

Shike H, Kadry Z, Imamura-Kawasawa Y, Greene W, Riley T, Nathan HM, Hasz RD, Jain A. Hepatitis C virus (HCV) RNA level in plasma and kidney tissue in HCV antibody-positive donors: Quantitative comparison. Clin Transplant 2018;32:e13358. [PMID: 30044009 DOI: 10.1111/ctr.13358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 06/22/2018] [Accepted: 07/21/2018] [Indexed: 01/15/2023]

Zarębska-Michaluk D, Jaroszewicz J, Janczewska E, Berak H, Horban A, Sitko M, Garlicki A, Dobracka B, Czauż-Andrzejuk A, Dybowska D, Halota W, Pawłowska M, Tudrujek-Zdunek M, Tomasiewicz K, Mazur W, Deroń Z, Belica-Wdowik T, Baka-Ćwierz B, Buczyńska I, Simon K, Piekarska A, Białkowska-Warzecha J, Lorenc B, Krygier R, Staniaszek A, Klapaczyński J, Citko J, Socha Ł, Wawrzynowicz-Syczewska M, Laurans Ł, Flisiak R. Interferon Free Therapy with and Without Ribavirin for Genotype 1 HCV Cirrhotic Patients in the Real World Experience. HEPATITIS MONTHLY 2018;18. [DOI: 10.5812/hepatmon.80761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]

Ramirez S, Bukh J. Current status and future development of infectious cell-culture models for the major genotypes of hepatitis C virus: Essential tools in testing of antivirals and emerging vaccine strategies. Antiviral Res 2018;158:264-287. [PMID: 30059723 DOI: 10.1016/j.antiviral.2018.07.014] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 07/17/2018] [Accepted: 07/20/2018] [Indexed: 02/08/2023]