Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection

Mina Nakagawa, Naoya Sakamoto, Mayumi Ueyama, Kaoru Mogushi, Satoshi Nagaie, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Hiroshi Tanaka, Nobuyuki Enomoto, Mamoru Watanabe

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24 Citations (Scopus)

Abstract

Background Pegylated-interferon-alpha 2b (PEG-IFN) plus ribavirin (RBV) therapy is currently the de-facto standard treatment for hepatitis C virus (HCV) infection. The aims of this study were to analyze the clinical and virological factors associated with a higher rate of response in patients with HCV genotype 1b infection treated with combination therapy. Methods We analyzed, retrospectively, 239 patients with chronic hepatitis C-1b infection who received 48 weeks of combination therapy. We assessed clinical and laboratory parameters, including age, gender, pretreatment hemoglobin, platelet counts, HCV RNA titer, liver histology, the number of interferon sensitivity determining region (ISDR) mutations and substitutions of the core amino acids 70 and 91. Drug adherence was monitored in each patient. We carried out univariate and multivariate statistical analyses of these parameters and clinical responses. Results On an intention-to-treat (ITT) analysis, 98 of the 239 patients (41%) had sustained virological responses (SVRs). Patients with more than two mutations in the ISDR had significantly higher SVR rates (P<0.01). Univariate analyses showed that stage of fibrosis, hemoglobin, platelet counts, ISDR mutations, serum HCV RNA level, and adherence to PEG-IFN plus RBV were significantly correlated with SVR rates. Multivariate analysis in subjects with good drug adherence extracted the number of ISDR mutations (two or more: odds ratio [OR] 5.181). Conclusions The number of mutations in the ISDR sequence of HCV-1b (≥2) is the most effective parameter predicting a favorable clinical outcome of 48-week PEGIFN plus RBV therapy in patients with HCV genotype 1b infection.

Original languageEnglish
Pages (from-to)656-665
Number of pages10
JournalJournal of gastroenterology
Volume45
Issue number6
DOIs
Publication statusPublished - 2010 Jun 1

Keywords

  • Chronic hepatitis C
  • Combination therapy
  • Hepatitis C virus (HCV)
  • Interferon sensitivity determining region (ISDR)
  • PEG-IFN plus RBV therapy

ASJC Scopus subject areas

  • Gastroenterology

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