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      The new paradigm of hepatitis C therapy: integration of oral therapies into best practices

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          Abstract

          SUMMARY. Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945–1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.

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          Most cited references107

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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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              Telaprevir for previously untreated chronic hepatitis C virus infection.

              In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients. In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with peginterferon-ribavirin for 12 weeks, followed by 36 weeks of peginterferon-ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response). Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P<0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group. Telaprevir with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ADVANCE ClinicalTrials.gov number, NCT00627926.).
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                Author and article information

                Journal
                J Viral Hepat
                J. Viral Hepat
                jvh
                Journal of Viral Hepatitis
                John Wiley & Sons
                1352-0504
                1365-2893
                November 2013
                07 October 2013
                : 20
                : 11
                : 745-760
                Affiliations
                [1 ]Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, MA, USA
                [2 ]Department of Medicine, J.W. Goethe University Hospital Frankfurt, Germany
                [3 ]Division of Infectious Diseases, San Diego School of Medicine, University of California La Jolla, CA, USA
                [4 ]Division of Infectious Diseases, Johns Hopkins University School of Medicine Baltimore, MD, USA
                [5 ]Division of Viral Hepatitis, Centers for Disease Control and Prevention Atlanta, GA, USA
                [6 ]Departments of Medicine and Psychiatry and Behavioral Sciences, Montefiore Medical Center, Albert Einstein College of Medicine Bronx, NY, USA
                [7 ]Center for Disease Analysis Louisville, CO, USA
                [8 ]Service d'Hepatologie, Hopital Beaujon, Assistance Publique Hopitaux de Paris Clichy, France
                [9 ]Service d'Hepatologie, Groupe Hospitalier Pitie-Salpetriere Paris, France
                [10 ]Gastroenterology and Hepatology Research Group, Duke Clinical Research Institute Durham, NC, USA
                [11 ]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health Baltimore, MD, USA
                [12 ]Fair Pricing Coalition and AIDS Action Baltimore Baltimore, MD, USA
                [13 ]Division of Infectious Disease, Beth Israel Deaconess Medical Center Boston, MA, USA
                [14 ]Massachusetts Department of Public Health, Bureau of Infectious Disease Boston, MA, USA
                [15 ]Division of Gastroenterology and Hepatology, Department of Internal Medicine, University at Buffalo Buffalo, NY, USA
                [16 ]Department of Medicine, Johns Hopkins University School of Medicine Baltimore, MD, USA
                [17 ]Division of Gastroenterology and Hepatology, Weill Cornell Medical College New York, NY, USA
                Author notes
                *Correspondence: Nezam H. Afdhal, MD, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, 110 Francis Street, Boston, MA 02215, USA., E-mail: nafdhal@ 123456caregroup.harvard.edu
                Article
                10.1111/jvh.12173
                3886291
                24168254
                2fcd5c7f-2789-445d-b32d-11fe72b1a7ae
                Copyright © 2013 John Wiley & Sons Ltd

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 23 August 2013
                : 24 August 2013
                Categories
                Review

                Infectious disease & Microbiology
                diagnosis,directly acting antiviral agents,health services,hepatitis c,pharmacoeconomics

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