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

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 HOMAIR>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.