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

Clin Exp Med. 2017 May;17(2):217-223. doi: 10.1007/s10238-016-0418-1. Epub 2016 Apr 15.

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.

Keywords: Gene polymorphism; Hepatocellular carcinoma; Interleukin-28B; Liver cirrhosis; rs12979860.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Genotyping Techniques
  • Hepatitis C, Chronic / complications
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / epidemiology
  • Liver Cirrhosis / genetics*
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Retrospective Studies
  • Young Adult

Substances

  • interferon-lambda, human
  • Interleukins
  • Interferons