Abstract

Background: Whether IL-28B polymorphism modulates the outcome of patients with HCVrelated cirrhosis remains unknown. Aim: to assess the effect of IL-28B polymorphism on the long-term course of patients with cirrhosis carrying HCV infection. Methods: IL-28B region (rs1297860) SNP was retrospectively determined by real-time PCR on DNA extracted from frozen blood EDTA or paraffin-embedded liver tissue. Differences in baseline demographical, virological, and clinical features of patients according to IL-28B genotype was assessed by the Student T, Fisher's exact andMantel-Haenszel tests respectively for continuous categorical and ordinal variables. Results:IL-28B genotype determinationwas available for 213 (45%)of all consecutive HCV-infected patients with either compensated or decompensated cirrhosis (Child class C excluded) enrolled in a prospective long-term follow-up study (53% males, mean age 57±8,5 years, 63% genotype 1, 55% received antiviral therapy, 26% attained sustained virological response (SVR). Overall, the frequency of CC, CT and TT genotype was 34%, 53% and 13%, with no difference between compensated or decompensated patients, at entry. CC genotype was observed in 24% of patients infected with HCV genotype 1 compared to 51% of subjects infected with other genotypes (P<0.0001). SVR was achieved in 51% of patients with CC genotype compared to 13% and 6% in those with CT and TT genotype, respectively (p<0.0001). IL-28B and SVR remained independently associated after adjustment for HCV genotype (p=0.003). Among the 85 treated patients without previous decompensation who did not achieve SVR, no association was found between IL-28B and development of hepatic decompensation, hepatocellular carcinoma and death after a median follow-up of 15 years Conclusion: The present study shows that IL-28B genotype has no impact on the outcome of patients with HCV-related cirrhosis. These results also confirm that, irrespective of genotype, IL-28B CC polymorphism is associated with the likelihood to achieve SVR and with non-1 HCV genotype infection.

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