Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy

Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3719-24. doi: 10.1073/pnas.1100349108. Epub 2011 Feb 14.

Abstract

Asian patients with chronic hepatitis C (CHC) are known to have better virological responses to pegylated (Peg) IFN-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics during treatment plays a role remains unclear. We enrolled 145 consecutive Taiwanese patients with CHC receiving Peg-IFN α-2a plus ribavirin for the study. Blood samples were taken more frequently at defined intervals in the first 3 d. Peg-IFN was administered at week 1. It was then administered weekly in combination with daily ribavirin for 24 or 48 wk. A mathematical model fitted to the observed HCV kinetics was constructed, which could interpret the transient HCV titer elevation after Peg-IFN treatment. The results demonstrated a comparable viral clearance rate (c = 3.45 ± 3.73) (day(-1), mean ± SD) but lower daily viral production rate (P = 10(6)-10(12)) in our patients than those reported previously in Western patients. Of 110 patients with a sustained virological response (SVR), 47 (43%) had a transient elevation of viral titer within 12 h (proportion of 12 h/3 d: 44% in non-SVR vs. 70% in SVR; P = 0.029). Among 91 patients with available rs8099917 data, patients with the TT genotype had an early surge of viral titer after therapy and a higher SVR and viral clearance rate than those with the GT genotype. In conclusion, Taiwanese patients with CHC receiving Peg-IFN plus ribavirin therapy have a lower daily viral production rate than Western patients, and the rs8099917 TT genotype may contribute to the increased viral clearance rate and better virological responses in these patients.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Genetic Predisposition to Disease*
  • Hepacivirus / physiology*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Kinetics
  • Models, Biological
  • Multivariate Analysis
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide / genetics*
  • Recombinant Proteins
  • Ribavirin / administration & dosage
  • Ribavirin / therapeutic use
  • Time Factors
  • Viral Load

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2a