Insulin resistance predicts rapid virologic response to peginterferon/ribavirin combination therapy in hepatitis C genotype 4 patients

Am J Gastroenterol. 2010 Sep;105(9):1970-7. doi: 10.1038/ajg.2010.110. Epub 2010 Mar 16.

Abstract

Objectives: In patients with chronic hepatitis C (CHC) of genotype 4, the predictors of rapid virologic response (RVR) have not been determined adequately. We aimed to assess which pretreatment variables might predict an RVR and a sustained virologic response (SVR).

Methods: A total of 131 non-diabetic, genotype 4 CHC patients were enrolled for analysis and treated with peginterferon-alpha-2b/ribavirin. Insulin resistance (IR) was evaluated by homeostasis model assessment-IR (HOMA-IR). Hepatitis C virus (HCV)-RNA levels were measured at baseline, during therapy and at follow-up.

Results: The overall SVR rate was 60.3%. The SVR rate in patients with an RVR was 100%. Age, HOMA-IR, fibrosis, severity of the steatosis, and HCV viral load were all significantly associated with RVR in the univariate analysis. After logistic regression, both HOMA-IR (odds ratio: 0.12, P=0.002) and HCV viral load (odds ratio: 1.43, P=0.02) remained independent variables associated with RVR. Age, HOMA-IR, viral load, fibrosis, RVR, and "complete" early virological response were all significantly associated with SVR in the univariate analysis. After logistic regression, fibrosis (odds ratio: 5.23, P=0.007), HOMA-IR (odds ratio: 14.29, P=0.004), and viral load (odds ratio: 0.16, P=0.005) were independent factors associated with SVR. By linear regression, body mass index (P=0.001) and waist circumference (P=0.0003) were independently associated with HOMA-IR.

Conclusions: IR is a major determinant of both RVR and SVR in genotype 4 CHC patients. HOMA-IR would seem to be a useful tool for predicting the response to therapy.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Body Mass Index
  • Chi-Square Distribution
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Humans
  • Insulin Resistance / genetics*
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Polyethylene Glycols / therapeutic use*
  • Prospective Studies
  • Recombinant Proteins
  • Ribavirin / therapeutic use*
  • Statistics, Nonparametric
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2b