Ultra-rapid virological response, young age, low γ-GT/ALT-ratio, and absence of steatosis identify a subgroup of HCV Genotype 3 patients who achieve SVR with IFN-α(2a) monotherapy

Dig Dis Sci. 2011 Nov;56(11):3296-304. doi: 10.1007/s10620-011-1933-2. Epub 2011 Oct 13.

Abstract

Background and aims: The standard treatment regimen for chronic HCV genotype 3 (HCV-G3) hepatitis consists of PEGylated interferon-α (IFN-α) and ribavirin at varying doses ranging from 400 to 1,200 mg and results in response rates of 80%. However, this therapy has substantial side-effects including anemia, is teratogenic, and costly. To reduce the side-effects of therapy, the role of monotherapy consisting of only IFN-α was investigated.

Methods: A retrospective analysis of individual therapy courses of HCV-G3-infected patients who were treated with IFN-α(2a) monotherapy or a combination therapy with attention to the treatment outcome and the presence of IL28B rs12979860 and IL28B rs8099917 single-nucleotide polymorphism genotypes was performed. Conventional prognostic features in each case were assessed as well.

Results: In the study, 15/30 (50%) of patients treated with IFN-α(2a) monotherapy and 32/36 (89%) treated with combination therapy achieved a sustained virological response (SVR). In addition, 7/11 (64%) of those treated initially with monotherapy and subsequently with combination therapy achieved an SVR. An "ultra-rapid" virological response occurring within 2 weeks of initiation of therapy (p = 0.005), young age (<40; p < 0.001) and low initial γ-GT/ALT-ratio (p = 0.03) were associated with a SVR to IFN-α(2a) monotherapy. An SVR in those treated with combination therapy was found to be associated with a rapid virological response (RVR) (p = 0.03). The absence of histologic steatosis was associated with SVR in all patient groups (p = 0.01). Therapy duration (24 vs. 48 weeks) did not affect the SVR in either group. As expected, combination therapy resulted in more hematological side-effects than did monotherapy.

Conclusions: An "ultra-rapid" virological response, young age, low initial γ-GT/ALT-ratio and absence of steatosis were each associated with an SVR in those receiving IFN-α(2a) monotherapy. Therefore, monotherapy in these patients should still be discussed independently of the existence of the IL28B polymorphisms.

MeSH terms

  • Adult
  • Age Factors
  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Fatty Liver / pathology
  • Fatty Liver / virology
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / pathology
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Liver / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Ribavirin / therapeutic use
  • Young Adult
  • gamma-Glutamyltransferase / blood

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Ribavirin
  • gamma-Glutamyltransferase
  • Alanine Transaminase