IINTERLEUKIN 28B RS12979860 C/T POLYMORPHISM AND SERUM CHOLESTEROL AS PREDICTORS OF FIBROSIS PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C AND PERSISTENTLY NORMAL TRANSAMINASES

The interleukin 28B (IL-28B) rs12979860 C/T polymorphism is a predictor of spontaneous and treatment-induced hepatitis C virus (HCV) clearance. The C/C genotype is associated with higher serum cholesterol, predictor of a favorable outcome in chronic hepatitis C. Whether IL-28B polymorphism and serum cholesterol play a role in modulating the history of mild hepatitis C is unknown. To clarify this issue, 93 untreated patients infected with HCV with normal or near-normal transaminases and an initial Ishak staging score =1 were investigated retrospectively in the longitudinal study (median histological follow-up of 10 years). An additional confirmatory cohort of 143 patients with chronic HCV infection and abnormal levels of transaminases was evaluated in the cross-sectional study. In the longitudinal study, at the end of follow-up, Ishak staging scores progressed more frequently among carriers of a T/* allele who had a baseline serum cholesterol =175mg/dl than in remaining patients: 6/36 (change =0), 15/45 (change 12), 6/12 (change =3), improvement chi-square P<0.02, OR 3.1, 95% C.I. 1.37.7. In the cross-sectional study, the frequency of patients carrying the T/T genotype or serum cholesterol values =175mg/dl increased starting from those with a staging score =2 (36/76, 47.4%), to those with a staging score of 34 (26/41, 63.4%) and to those with a staging score of 56 (20/26, 76.9%, P<0.01 for linear trend). In conclusion, the interaction between IL-28B rs12979860 T/T genotype and low serum cholesterol concentration is an independent predictor of a worse disease course among patients infected with HCV with normal or near-normal transaminases. J. Med. Virol. 84:747755, 2012. (C) 2012 Wiley Periodicals, Inc.