Using Early Viral Kinetics to Predict Antiviral Outcome in Response-Guided Pegylated Interferon Plus Ribavirin Therapy Among Patients With Hepatitis C Virus Genotype 1

J Gastroenterol. 2014 Apr;49(4):737-47. doi: 10.1007/s00535-013-0824-z. Epub 2013 May 21.

Abstract

Background: HCV kinetics during treatment demonstrated strong association with the antiviral outcome of patients treated with pegylated interferon (Peg-IFN) plus ribavirin. However, the relationship between HCV kinetics and pre-treatment factors remains unclear.

Methods: Of 547 patients with HCV genotype 1 treated with Peg-IFN alfa-2b plus ribavirin, 401 completed the response-guided therapy and were assessed for per protocol analysis.

Results: The sustained virologic response (SVR) rate was 53 % for all patients, 60 % for those with genotype TT, and 19 % for those with genotype TG/GG according to IL28B (rs8099917) single nucleotide polymorphisms. The SVR rates increased with HCV decrease at week 4; 4 % (2/56) with <1 log10 decrease, 13 % (7/56) with 1-2 log10 decrease, 51 % (44/87) with 2-3 log10 decrease, 64 % (56/87) with 3-4 log10 decrease, 88 % (72/82) with more than 4 log10 decrease but with detectable HCV RNA and 100 % (33/33) with undetectable HCV RNA (p < 0.001). Similarly, SVR rates increased step-by-step in proportion to HCV decrease in both IL28B TT and TG/GG groups, showing almost the same SVR rates for the same conditions. In multivariate analysis, age (p = 0.005) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with SVR. Advanced liver fibrosis (p = 0.004) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with non-response.

Conclusions: The magnitude of the HCV decrease at week 4 seems to be the most reliable marker for predicting antiviral outcome after starting Peg-IFN plus ribavirin therapy.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide
  • Predictive Value of Tests
  • RNA, Viral / blood*
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Ribavirin / therapeutic use*
  • Time Factors
  • Viral Load

Substances

  • Antiviral Agents
  • IFNL3 protein, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2b