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

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.

• Authors: Elisabetta Degasperi, Luca Valenti, Alessio Aghemo, Raffaele De Francesco, Mariagrazia Rumi, Roberta Soffredini, Lorena Donnici, Cristina Cheroni, Silvia Fargion, Valeria Zanoni, Emanuela Orsi, Massimo Colombo
• Journal: Antiviral therapy (Antivir Ther) Vol. 19 Issue 8 Pg. 747-53 ( 2014) ISSN: 2040-2058 [Electronic] England
• PMID: 24523350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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