Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin

N. Hiramatsu, T. Oze, T. Yakushijin, Y. Inoue, T. Igura, K. Mochizuki, K. Imanaka, A. Kaneko, M. Oshita, H. Hagiwara, E. Mita, T. Nagase, T. Ito, Y. Inui, T. Hijioka, K. Katayama, S. Tamura, H. Yoshihara, Y. Imai, M. KatoY. Yoshida, T. Tatsumi, K. Ohkawa, S. Kiso, T. Kanto, A. Kasahara, T. Takehara, N. Hayashi

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62 Citations (Scopus)

Abstract

The impact of ribavirin exposure on virologic relapse remains controversial in combination therapy with pegylated interferon (Peg-IFN) and ribavirin for patients with chronic hepatitis C (CH-C) genotype 1. The present study was conducted to investigate this. Nine hundred and eighty-four patients with CH-C genotype 1 were enrolled. The drug exposure of each medication was calculated by averaging the dose actually taken. For the 472 patients who were HCV RNA negative at week 24 and week 48, multivariate logistic regression analysis showed that the degree of fibrosis (P = 0.002), the timing of HCV RNA negativiation (P < 0.001) and the mean doses of ribavirin (P < 0.001) were significantly associated with relapse, but those of Peg-IFN were not. Stepwise reduction of the ribavirin dose was associated with a stepwise increase in relapse rate from 11% to 60%. For patients with complete early virologic response (c-EVR) defined as HCV RNA negativity at week 12, only 4% relapse was found in patients given ≥12 mg/kg/day of ribavirin and ribavirin exposure affected the relapse even after treatment week 12, while Peg-IFN could be reduced to 0.6 μg/kg/week after week 12 without the increase of relapse rate. Ribavirin showed dose-dependent correlation with the relapse. Maintaining as high a ribavirin dose as possible (≥12 mg/kg/day) during the full treatment period can lead to suppression of the relapse in HCV genotype 1 patients responding to Peg-IFN alpha-2b plus ribavirin, especially in c-EVR patients.

Original languageEnglish
Pages (from-to)586-594
Number of pages9
JournalJournal of Viral Hepatitis
Volume16
Issue number8
DOIs
Publication statusPublished - 2009 Aug 1
Externally publishedYes

Keywords

  • Chronic hepatitis C
  • Drug exposure
  • Pegylated interferon plus ribavirin
  • Virologic relapse

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

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    Hiramatsu, N., Oze, T., Yakushijin, T., Inoue, Y., Igura, T., Mochizuki, K., Imanaka, K., Kaneko, A., Oshita, M., Hagiwara, H., Mita, E., Nagase, T., Ito, T., Inui, Y., Hijioka, T., Katayama, K., Tamura, S., Yoshihara, H., Imai, Y., ... Hayashi, N. (2009). Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin. Journal of Viral Hepatitis, 16(8), 586-594. https://doi.org/10.1111/j.1365-2893.2009.01106.x