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      Efficacy of 24-Week Pegylated Interferon Alpha and Ribavirin Combination Therapy in Highly Selected Patients Infected With Hepatitis C Virus Genotype 1

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          Abstract

          Background:

          Previous studies using pegylated interferon (Peg-IFN) and ribavirin (RBV) combination therapy suggested that patients with hepatitis C virus (HCV) genotype 1 and low pretreatment HCV RNA level who achieved rapid virological response (RVR) can be treated for 24 weeks without compromising sustained virological response (SVR) rate.

          Objectives:

          The current study aimed to investigate the efficacy of Peg-IFN-alfa-2a plus RBV administered for a 24-week treatment course in patients with chronic HCV genotype 1 infection and possessing the following criteria: low baseline serum HCV RNA level, absence of significant fibrosis and achievement of RVR.

          Patients and Methods:

          In this case-control study, 20 patients with HCV genotype 1 infection and favorable baseline characteristics and on-treatment response were treated with Peg-IFN and RBV for 24 weeks as the case group. Furthermore, 23 patients with the same characteristics who underwent a 48-week treatment course were selected as the control group.

          Results:

          The majority of patients had no fibrosis on liver elastography. There was no statistical difference regarding age, gender, alanine transaminase (ALT) level, rs12979860 polymorphism and the level of fibrosis between the two studied groups. All patients in the 24-week treatment course achieved SVR and all the subjects who received the 48-week treatment course achieved SVR as well (P > 0.99).

          Conclusions:

          The current study confirmed that the efficacy of a 24-week regimen of Peg-IFN-alfa-2a plus RBV was similar to the 48-week treatment in the patients infected with HCV genotype 1, and low baseline HCV RNA level who achieved RVR. Response guided therapy can be efficient and cost-effective among the selected HCV genotype 1-infected patients.

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          Most cited references22

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          Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.

          A sustained virological response (SVR) rate of 41% has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this randomised trial, peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin. 1530 patients with chronic hepatitis C were assigned interferon alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 1000-1200 mg/day orally, peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin, or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000-1200 mg/day for 48 weeks. The primary endpoint was the SVR rate (undetectable hepatitis C virus [HCV] RNA in serum at 24-week follow-up). Analyses were based on patients who received at least one dose of study medication. The SVR rate was significantly higher (p=0.01 for both comparisons) in the higher-dose peginterferon group (274/511 [54%]) than in the lower-dose peginterferon (244/514 [47%]) or interferon (235/505 [47%]) groups. Among patients with HCV genotype 1 infection, the corresponding SVR rates were 42% (145/348), 34% (118/349), and 33% (114/343). The rate for patients with genotype 2 and 3 infections was about 80% for all treatment groups. Secondary analyses identified bodyweight as an important predictor of SVR, prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight (mg/kg). Side-effect profiles were similar between the treatment groups. In patients with chronic hepatitis C, the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin. The benefit is mostly achieved in patients with HCV genotype 1 infections.
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            Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.

            Treatment with pegylated interferon (peginterferon) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or standard dose of ribavirin. Randomized, double-blind trial. 99 international centers. 1311 patients with chronic hepatitis C. Peginterferon-alpha2a, 180 microg/wk, for 24 or 48 weeks plus a low-dose (800 mg/d) or standard weight-based dose (1000 or 1200 mg/d) of ribavirin. Sustained virologic response: undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up. Overall and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribavirin was statistically superior to low-dose ribavirin. In patients with HCV genotype 1, absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2% (95% CI, 3.6% to 18.9%) and 11.9% (CI, 4.7% to 18.9%), respectively, between standard- and low-dose ribavirin. Sustained virologic response rates for peginterferon-alpha2a and standard-dose ribavirin for 48 weeks were 63% (CI, 59% to 68%) overall and 52% (CI, 46% to 58%) in patients with HCV genotype 1. In patients with HCV genotypes 2 or 3, the sustained virologic response rates in the 4 treatment groups were not statistically significantly different. Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.
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              Treating viral hepatitis C: efficacy, side effects, and complications.

              M P Manns (2006)
              The treatment of hepatitis C has dramatically improved over the past decade. Unlike any other chronic viral infection, a significant proportion of patients with chronic hepatitis C can be cured. However, the current standard therapy--pegylated interferon alpha and ribavirin--has its limitations. Limited efficacy in patients with hepatitis C virus (HCV) genotype 1 and the side effect profile will necessitate the development of new therapeutic approaches. This review describes the efficacy and optimisation of the current standard therapy of hepatitis C and its problems in special patient populations. New treatment directions beyond interferon alpha based therapies are on the horizon.
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                Author and article information

                Journal
                Hepat Mon
                Hepat Mon
                10.5812/hepatmon
                Kowsar
                Hepatitis Monthly
                Kowsar
                1735-143X
                1735-3408
                01 January 2015
                January 2015
                : 15
                : 1
                : e24955
                Affiliations
                [1 ]Iran Hepatitis Network, Tehran, IR Iran
                [2 ]Middle East Liver Diseases Center (MELD), Tehran, IR Iran
                [3 ]Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IR Iran
                Author notes
                [* ]Corresponding Author: Maryam Keshvari, Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IR Iran. Tel: +98-2188601501-30, Fax: +98-2166900386, E-mail: m.keshvari@ 123456ibto.ir
                Article
                10.5812/hepatmon.24955
                4330713
                25741374
                0953fdb5-98d4-4a7b-9d77-e26dd1b86106
                Copyright © 2015, Kowsar Corp.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

                History
                : 28 October 2014
                : 03 December 2014
                : 31 December 2014
                Categories
                Research Article

                Infectious disease & Microbiology
                hepatitis c,peg-interferon alfa-2a,viral load
                Infectious disease & Microbiology
                hepatitis c, peg-interferon alfa-2a, viral load

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