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BACKGROUND AND AIMS:Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography. METHODS:Seven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan® in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping. RESULTS:CC(rs12979860) was more common among HCV genotype 2 or 3 infected treatment-naïve patients than among those infected with genotype 1 (P<0.0001). Additionally CC(rs12979860) among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004), and higher AST to platelet ratio index (APRI; p = 0.02) as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CC(rs12979860) was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients. CONCLUSION:This study confirms previous reports that the CC(rs12979860) SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.