July 7, 2011

Genetic variation in IL28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection

Hepatology. 2011 Jun 30. doi: 10.1002/hep.24503. [Epub ahead of print]

Marabita F, Aghemo A, De Nicola S, Rumi MG, Cheroni C, Scavelli R, Crimi M, Soffredini R, Abrignani S, De Francesco R, Colombo M.

INGM - Istituto Nazionale Genetica Molecolare Milano, Italy.

Abstract

Polymorphisms in the IL28B region are associated with spontaneous and treatment-induced viral clearance in Hepatitis C virus (HCV) infection. Nevertheless, it is unknown whether genetic variation at the IL28B locus influences the natural history of chronic HCV infection. Thus, we asked if an association between IL28B polymorphisms and liver fibrosis progression existed. We studied 247 consecutive patients with chronic HCV, an accurate estimate of the date of infection and a liver biopsy performed before any treatment. No patient had a history of alcohol abuse or co-infection with other viruses. We assessed the role of rs8099917 and rs12979860 polymorphisms and the effect of host and environmental factors on fibrosis progression. Blood transfusion (75%) was the main modality of infection. The median age at infection was 21 years and the median interval between infection and liver biopsy was 25 years. 129 patients (52%) were infected by HCV-1, 74 (30%) by HCV-2, 34 (14%) by HCV-3 and 10 (4%) by HCV-4. Bridging fibrosis/cirrhosis (Ishak≥4) was detected in 24% of patients. Age at infection had a marked effect on fibrosis progression by both a linear model and Cox-proportional hazard regression (P<2E-16). A 12.1% increase in the hazard of advanced fibrosis was estimated for each additional year at infection, suggesting that this is the major explanatory variable in this cohort. Male gender (P<0.05), HCV genotype 3 (P<0.001) and steatosis (P<0.05) were also associated to faster fibrosis progression. Conversely, the two IL28B polymorphisms had no impact on fibrosis progression. Conclusions: In HCV patients with known date of infection IL28B genotype was not associated with fibrosis progression rate or with the risk of developing advanced liver fibrosis. (HEPATOLOGY 2011.).

Copyright © 2011 American Association for the Study of Liver Diseases.

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