Impact of Ribavirin Dosage in Chronic Hepatitis C Patients Treated With Simeprevir, Pegylated Interferon Plus Ribavirin Combination Therapy

J Med Virol. 2016 Oct;88(10):1776-84. doi: 10.1002/jmv.24528. Epub 2016 Mar 29.

Abstract

The factors associated with sustained virologic response (SVR) in chronic hepatitis C (CH-C) genotype 1 patients treated with simeprevir (SMV), pegylated interferon (Peg-IFN) plus ribavirin (RBV) triple therapy have not been fully investigated. Two hundred and twenty-nine treatment-naïve CH-C patients treated with SMV triple therapy were enrolled in this study. The overall SVR rate was 87% in per-protocol analysis. In multivariate analysis, the interleukin (IL) 28B genotype (rs8099917, TT vs. non-TT, odds ratio [OR]: 0.044, P = 0.001) and RBV dose (< 10/10-12/ ≥ 12 mg/kg/day, OR: 4.513, P = 0.041) were significant factors associated with SVR. In patients with the IL28B non-TT genotype, RBV dose affected SVR dose-dependently in stratified analysis of RBV dose (P = 0.015); it was 44% (8/18) for patients administered <10 mg/kg/day of RBV, 78% (14/18) for those administered 10-12 mg/kg/day of RBV, and 100% (3/3) for those administered ≥12 mg/kg/day of RBV, whereas in patients with the IL28B TT genotype, a significant correlation between SVR and RBV dose was not observed (P = 0.229). Regarding RBV dose reduction of less than 10 mg/kg/day, the inosine triphosphate pyrophosphatase (ITPA) genotype (rs1127354, CC vs. non-CC, OR: 0.239, P = 0.003) and age (by 1 y.o., OR: 1.084, P = 0.002) were significant independent factors. RBV dosage affected SVR dose-dependently in patients with the IL28B non-TT genotype treated with SMV triple therapy. Special attention to anemia progression and RBV dosage should be paid to aged patients with the ITPA CC genotype. J. Med. Virol. 88:1776-1784, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: chronic hepatitis C; interleukin 28B; ribavirin dose; simeprevir; sustained virologic response.

MeSH terms

  • Aged
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide
  • Pyrophosphatases / genetics
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Ribavirin / administration & dosage*
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use
  • Simeprevir / administration & dosage*
  • Simeprevir / therapeutic use
  • Sustained Virologic Response*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • IFNL3 protein, human
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • Simeprevir
  • Pyrophosphatases
  • ITPA protein, human
  • peginterferon alfa-2a