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      Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections

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          Abstract

          Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus (HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.

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          Most cited references156

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          Liver fibrosis.

          Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-beta1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans is unknown. This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies.
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            Diagnosis, management, and treatment of hepatitis C: an update.

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              Boceprevir for untreated chronic HCV genotype 1 infection.

              Peginterferon-ribavirin therapy is the current standard of care for chronic infection with hepatitis C virus (HCV). The rate of sustained virologic response has been below 50% in cases of HCV genotype 1 infection. Boceprevir, a potent oral HCV-protease inhibitor, has been evaluated as an additional treatment in phase 1 and phase 2 studies. We conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were randomly assigned to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (the control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks, and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks. Nonblack patients and black patients were enrolled and analyzed separately. A total of 938 nonblack and 159 black patients were treated. In the nonblack cohort, a sustained virologic response was achieved in 125 of the 311 patients (40%) in group 1, in 211 of the 316 patients (67%) in group 2 (P<0.001), and in 213 of the 311 patients (68%) in group 3 (P<0.001). In the black cohort, a sustained virologic response was achieved in 12 of the 52 patients (23%) in group 1, in 22 of the 52 patients (42%) in group 2 (P=0.04), and in 29 of the 55 patients (53%) in group 3 (P=0.004). In group 2, a total of 44% of patients received peginterferon-ribavirin for 28 weeks. Anemia led to dose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2%, respectively. The addition of boceprevir to standard therapy with peginterferon-ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection. The rates were similar with 24 weeks and 44 weeks of boceprevir. (Funded by Schering-Plough [now Merck]; SPRINT-2 ClinicalTrials.gov number, NCT00705432.).
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                Author and article information

                Journal
                World J Hepatol
                WJH
                World Journal of Hepatology
                Baishideng Publishing Group Inc
                1948-5182
                8 November 2016
                8 November 2016
                : 8
                : 31
                : 1295-1308
                Affiliations
                Daniel Fuster, Arantza Sanvisens, Jordi Tor, Robert Muga, Department of Internal Medicine, Addiction Unit, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain
                Ferran Bolao, Department of Internal Medicine, Hospital Universitari de Bellvitge, IDIBELL, 08907 L’Hospitalet de Llobregat, Spain
                Inmaculada Rivas, Municipal Center for Substance Abuse Treatment (Centro Delta), IMSP, 08916 Badalona, Spain
                Author notes

                Author contributions: Fuster D performed the literature search and drafted the first version of the manuscript; Sanvisens A and Muga R provided feedback for the first version and suggested additional references; all authors edited and provided feedback around the updated version of the review and approved the final version of the manuscript.

                Supported by Ministry of Economy and Competitiveness, Institute of Health Carlos, ISCIII: European fund for regional development (FEDER), Nos. RETICS RD 12/0028/0006 and RD16/0017/0003 ; Ministry of Health, Social Services, and Equality, Nos. PNSD 2014/042 and PNSD 2015/027.

                Correspondence to: Daniel Fuster, MD, PhD, Department of Internal Medicine, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Carretera de Canyet, S/N, 08916 Badalona, Spain. dfuster.germanstrias@ 123456gencat.cat

                Telephone: +34-934-978908 Fax: +34-934-978768

                Article
                jWJH.v8.i31.pg1295
                10.4254/wjh.v8.i31.1295
                5099582
                27872681
                d5a73ee3-e598-428e-a93e-11e80bd23f07
                ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 4 May 2016
                : 4 August 2016
                : 27 August 2016
                Categories
                Review

                hepatitis c virus,human immunodeficiency virus,hepatitis c virus/human immunodeficiency virus co-infection,liver,alcohol

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