Interleukin 28B genotype and insulin resistance in chronic hepatitis C patients

Antivir Ther. 2014;19(8):747-53. doi: 10.3851/IMP2743. Epub 2014 Feb 12.

Abstract

Background: In patients with chronic HCV infection, an association between IL28B genotype and insulin-resistance (IR), known predictors of sustained virological response (SVR) to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, has been reported. The aim of this study was to investigate the association of IR and IL28B genotype in two cohorts of well-characterized HCV patients.

Methods: A total of 480 non-diabetic HCV patients were analysed: 391 patients who received PEG-IFN/RBV in the MIST study and 89 previously reported patients followed at a metabolic liver diseases centre (Division of Internal Medicine, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, Italy). All were tested for IL28B rs12979860 single nucleotide polymorphism by real-time PCR and had IR measured by HOMA-IR. Staging of liver disease through liver biopsy was available for all patients.

Results: Overall, 164 patients (34%) were IL28B CC. Mean HOMA-IR values (±sd) did not differ according to IL28B genotype, being respectively 1.14 ±0.79 in CC versus 1.14 ±0.78 in CT/TT (P=1.0) in the first, and 2.4 ±1.0 versus 2.5 ±1.0 (P=0.7) in the second cohort. HOMA-IR>2 was not associated with IL28B genotype: 16/132 (12%) CC versus 31/259 (12%) CT/TT (P=1.0) in the first cohort and 16/32 (50%) versus 37/57 (65%; P=0.18) in the second. This held true also when using different HOMA cutoffs (>2.5, >3.0, >3.5 and >4.0). In the MIST cohort, HOMA-IR>2 did not influence treatment outcome, SVR rates being 28/47 (60%) in HOMA-IR>2 versus 214/344 (62%) in HOMA-IR≤2 (P=0.8). IL28B genotype was a strong predictor of SVR: 84% (111/132) in CC versus 51% (131/259) in CT/TT patients (P<0.0001).

Conclusions: In two cohorts of non-diabetic HCV patients where IL28B genotype predicted treatment outcome, we found no association between IL28B genotype and HOMA-IR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antiviral Agents / therapeutic use
  • Cohort Studies
  • Female
  • Genotype*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / metabolism*
  • Hepatitis C, Chronic / virology
  • Humans
  • Insulin Resistance*
  • Interferons
  • Interleukins / genetics*
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interleukins
  • Interferons