Common Variation of IL28 affects Gamma-GTP Levels and Inflammation of the Liver in Chronically Infected Hepatitis C Virus Patients Author Names and affiliations:

Background/Aims: Common genetic variation at the IL28 locus has been found to affect the response of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. An allele associated with a favorable response (rs8099917 T), which is the major allele in the majority of Asian, American and European populations, has also been found to be associated with spontaneous eradication of the virus. Methods: As no studies have yet analyzed the effect of the polymorphism on biochemical and inflammatory changes in chronic infection, we analyzed a cohort of patients with chronic hepatitis C (n=364) for the effect of the IL28 polymorphism on viral, biochemical and histological findings. Results: We found that the proportion of HCV wild type core amino acids 70 and 91 was significantly greater (P=1.21x10 and 0.034) and levels of gamma GTP significantly lower (P=0.001) in patients homozygous for the IL28 major allele. We also found that inflammation activity and fibrosis of the liver were significantly more severe in patients homozygous for the IL28 major allele (P=0.025 and 0.036, respectively). Although the higher gamma GTP levels were also associated with higher inflammatory activity and fibrosis, multivariate analysis showed that only IL28 allele polymorphism, sex, alcohol consumption and liver fibrosis were independently associated with gamma GTP levels (P= 0.001, 0.0003, 0.0013, and 0.0348, respectively). Conclusions: These results suggest that different cytokine profiles induced by the IL28 polymorphism resulted in different biochemical and inflammatory conditions during chronic HCV infection and contribute to the progression of liver diseases. (248 words)