Insulin resistance predicts sustained virological response to treatment of chronic hepatitis C independently of the IL28b rs12979860 polymorphism

Aliment Pharmacol Ther. 2013 Jan;37(1):74-80. doi: 10.1111/apt.12113. Epub 2012 Nov 5.

Abstract

Background: Insulin resistance has been strongly associated with the attainment of sustained viral response (SVR) in hepatitis C patients.

Aim: To determine, in a cohort of Spanish patients with chronic hepatitis C treated with peginterferon plus ribavirin (P+R), whether insulin resistance predicts SVR independently of interleukin-28B rs12979860 polymorphism.

Methods: Insulin resistance was measured as [HOMA-IR = Insulin (IU/mL)*glucose (mmol/L)/22.5]. Genotype, viral load and histological fibrosis using Scheuer score were also measured. Binary logistic regression analysis was used for statistical purposes.

Results: In a cohort of 240 patients [78% genotype 1, 24% showing advanced fibrosis, 71% high viral load (≥800 000 IU/mL), 31% IL28b genotype CC and 50% with HOMA >2] treated with P+R, 126 (53%) reached SVR. HOMA-IR index (HOMA <2: 63% vs. HOMA >2: 42%; P = 0.001 and IL28b (genotype CC: 68% vs. genotype CT/TT: 45%; P = 0.002) were significantly associated with SVR. In multivariable logistic regression analysis in the overall cohort, variables independently associated were: viral genotype OR: 0.29 (95% CI: 0.11-0.78), P = 0.01; fibrosis OR: 1.62 (95% CI: 1.22-2.16), P = 0.001; HOMA-IR OR: 1.22 (95% CI: 1.02-1.47), P = 0.03; and IL28B genotype OR: 2.43 (95% CI: 1.45-4.07), P = 0.001. The analyses also showed that degree of steatosis, HOMA-IR >2, mild fibrosis and IL28B CC genotype were significantly related to SVR in patients infected with HCV genotypes 1&4, but not in those with genotypes 2&3. No differences were seen in glucose, insulin level or HOMA-IR index segregated according to IL28B genotypes.

Conclusion: Our results suggest that insulin resistance, fibrosis stage and IL28B polymorphisms were independent variables associated with sustained viral response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Blood Glucose / analysis
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Genotyping Techniques
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Insulin / blood
  • Insulin Resistance / genetics*
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide*
  • Recombinant Proteins / therapeutic use
  • Regression Analysis
  • Ribavirin / therapeutic use
  • Treatment Outcome
  • Viral Load

Substances

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