Peginterferon Alfa-2a and Ribavirin in Patients with Chronic Hepatitis C Who Have Failed Prior Treatment

Mitchell L. Shiffman, Adrian M. Di Bisceglie, Karen L. Lindsay, Chihiro Morishima, Elizabeth C. Wright, Gregory T. Everson, Anna S. Lok, Timothy R. Morgan, Herbert L. Bonkovsky, William M. Lee, Jules L. Dienstag, Marc G. Ghany, Zachary D. Goodman, James E. Everhart

Research output: Contribution to journalArticle

458 Scopus citations

Abstract

Background & Aims: The most effective therapy currently available for treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin. This study evaluated the effectiveness of this treatment in patients who were nonresponders to previous interferon-based therapy. Methods: The first 604 patients enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial were evaluated. All were HCV RNA positive, previous nonresponders to interferon, with or without ribavirin, and had bridging fibrosis or cirrhosis on liver biopsy (Ishak fibrosis stage 3-6). Patients were retreated with peginterferon alfa-2a 180 μg/wk plus ribavirin 1000-1200 mg/day. Those with no detectable HCV RNA in serum at week 20 continued treatment for a total of 48 weeks and were then followed for an additional 24 weeks. Results: Thirty-five percent of patients had no detectable HCV RNA in serum at treatment week 20, and 18% achieved sustained virologic response (SVR). Factors associated with an SVR included previous treatment with interferon monotherapy, infection with genotypes 2 or 3, a lower AST: ALT ratio, and absence of cirrhosis. Reducing the dose of ribavirin from ≥80% to ≤60% of the starting dose during the first 20 weeks of treatment was associated with a decline in SVR from 21% to 11% (P ≤ 0.05). In contrast, reducing the dose of peginterferon or reducing ribavirin after week 20, when HCV RNA was already undetectable, did not significantly affect SVR. Conclusions: Selected nonresponders to previous interferon-based therapy can achieve SVR following retreatment with peginterferon alfa-2a and ribavirin.

Original languageEnglish (US)
Pages (from-to)1015-1023
Number of pages9
JournalGastroenterology
Volume126
Issue number4
DOIs
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Shiffman, M. L., Di Bisceglie, A. M., Lindsay, K. L., Morishima, C., Wright, E. C., Everson, G. T., Lok, A. S., Morgan, T. R., Bonkovsky, H. L., Lee, W. M., Dienstag, J. L., Ghany, M. G., Goodman, Z. D., & Everhart, J. E. (2004). Peginterferon Alfa-2a and Ribavirin in Patients with Chronic Hepatitis C Who Have Failed Prior Treatment. Gastroenterology, 126(4), 1015-1023. https://doi.org/10.1053/j.gastro.2004.01.014