IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: Role in the course of chronic viral hepatitis and the development of HCC

Background & Aims: A single nucleotide polymorphism (rs12979860 C/T) 3 kb upstream of the interleukin 28B (IL-28B) gene was shown to be associated with hepatitis C clearance. We verified whether this association also translates into a different genotype distribution at the end of the disease trajectory. Methods: A RFLP-PCR technique was used to genotype 412 patients with cirrhosis due to hepatitis C (n = 199), hepatitis B (n = 75), alcohol (n = 110), and other causes (n = 28), of whom 256 underwent liver transplantation (OLT). Hepatocellular carcinoma (HCC) was demonstrated in the native liver of 85 OLT patients, 52 with viral cirrhosis, and 33 with non-viral cirrhosis respectively. A group of 292 patients (235 HCV and 57 HBV positive) with mild chronic hepatitis and 344 healthy subjects served as controls. Results: A significant difference (p = 0.0005) was observed in IL-28B rs12979860 genotype frequencies between patients with viral cirrhosis (C/C = 99, C/T = 137, T/T = 38) and those with non-viral cirrhosis (C/C = 72, C/T = 58, T/T = 8). Patients with HCV related cirrhosis carried more frequently the T/T genotype in comparison to mild hepatitis C or HBV-related cirrhosis. IL-28B rs12979860 genotype frequencies were C/C = 23, C/T = 50, T/T = 12 among OLT patients with cirrhosis complicated by HCC, and C/C = 79, C/T = 78, T/T = 14 among patients with cirrhosis not complicated by HCC (p <0.005). Conclusions: IL-28B rs12979860 C/T polymorphism T allele is more prevalent in patients with viral cirrhosis due to HCV in comparison to other aetiologies and to patients with mild chronic hepatitis C. Among OLT patients, carriage of this allele seems to augment the risk of developing HCC.