Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis.

Abstract

Persistent hepatitis C virus (HCV) infection is associated with progressive hepatic fibrosis and ultimately hepatocellular carcinoma. The interleukin-28B (IL28B) rs12979860 polymorphism is associated with fibrosis progression in chronic HCV infection. IL28B encodes interferon-λ, which has both antiviral and anti-proliferative properties. This study aimed to determine whether IL28B rs12979860 polymorphism is also associated with development of hepatocellular carcinoma both in chronic HCV infection and in non-viral-related cirrhosis. Real-time polymerase chain reaction and melting curve analyses were used to genotype 311 patients who underwent liver transplantation for HCV cirrhosis (n=202) or alcoholic cirrhosis (n=109). HCV patients were older (p=0.012) and less likely males (p<0.001) than patients with alcoholic cirrhosis. IL28B rs12979860 TT genotype [OR 6.08, 95% CI 2.11-17.53; p<0.001] and T allele carriage (CT+TT; OR 2.3, CI 95% 1.42-3.72; p=0.001) were more frequent among HCV patients and, among them, more common in patients infected with HCV genotype 1 (CT+TT; OR 1.79, CI 95% 1.03-3.09; p=0.009). Incidence of hepatocellular carcinoma was higher in HCV cirrhosis (OR 2.7, CI 95% 1.5-4.7; p<0.001), with no differences according to HCV genotype. IL28B genotype distribution was similar among patients with or without hepatocellular carcinoma, in both HCV patients regardless viral genotype (p=0.84) and alcoholic patients (p=0.91). Multivariate analysis showed that older age (OR 1.06, CI 95% 1.02-1.1; p=0.003) and male gender (OR 2.49, CI 95% 1.24-5; p=0.01) were independent risk factors for hepatocellular carcinoma in HCV patients. In summary, the current study did not find a significant association between IL28B rs12979860 polymorphism and hepatocarcinogenesis.