Role of IL28-B polymorphisms in the treatment of chronic hepatitis B HBeAg-negative patients with peginterferon

Antiviral Res. 2014 Feb:102:35-43. doi: 10.1016/j.antiviral.2013.11.014. Epub 2013 Dec 4.

Abstract

Interleukin (IL)28-B polymorphism has been related to interferon response in the treatment of hepatitis C, but its role in chronic hepatitis B (CHB) therapy is still poorly understood. We aimed to investigate the effect of IL28-B polymorphisms in the treatment with pegylated-interferon (PEG-IFN) of patients with CHB. We retrospectively analyzed 190 patients with chronic hepatitis B e antigen (HBeAg) negative, genotype A (22%), B (12%), C (10%), D (33%), E (20%), treated with PEG-IFN alfa-2a for 48weeks; genotype analysis was performed for IL28-B polymorphisms rs12979860, rs8099917 and rs12980275 according to virological, serological and biochemical response. During 2years of follow-up 12 patients (6.3%) cleared hepatitis B surface antigen (HBsAg) with seroconversion, 40 (21%) obtained a negative viral load and 104 (54.7%) gained a biochemical response. We found a difference of distribution of rs12979860 CC genotype among different ethnicity (p=0.013). Rs12979860 CC genotype was significantly associated with serological and virological response (p<0.001); rs8099917 TT and rs12980275 AA genotypes were mostly related with virological response (p<0.001). In multivariate logistic analysis rs12979860 CC was predictive of virological response (OR=4.290; CI=1.589-11.580, p=0.004) and serological response (OR=10.129; CI=2.440-42.044; p<0.001). Rs8099917 TT was predictive only of virological response (OR=3.746, CI=1.235-11.355; p=0.020). The E genotype was a negative predictive factor of virological response (OR=0.057; CI=0.014-0.238; p<0.001). IL28-B polymorphisms are related to different response in the treatment of CHB HBeAg-negative with PEG-IFN, and the E genotype is a novel negative predictive factor.

Keywords: ALT; CHB; HBV; HBV genotype; HBeAg; HBeAg-negative; HBsAg; HCC; Hepatitis B; IL28-B; IQR; NA; PEG-IFN; PEG-INF; Predictive factor; SNP; SVR; UNL; alanine aminotransferase; cccDNA; chronic hepatitis B; closed circular DNA; hepatitis B surface antigen; hepatitis B virus; hepatitis e antigen; hepatocellular carcinoma; inter-quartile range; nucleos(t)ide analogues; pegylated interferon; qHBsAg; quantitative HBsAg; single nucleotide polymorphism; sustained virological response; upper normal level.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Genotype
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / classification
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Genetic*
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Hepatitis B e Antigens
  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Interferons
  • peginterferon alfa-2a