IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen-negative patients with chronic hepatitis B

Hepatology. 2013 Mar;57(3):890-6. doi: 10.1002/hep.25749. Epub 2012 Dec 20.


Interleukin (IL)28B polymorphisms have been associated with interferon (IFN)-induced viral clearance in patients with chronic hepatitis C. Whether this is also true for patients with the difficult-to-cure hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) is unknown. One hundred and one HBeAg-negative patients (92% genotype D) with compensated CHB (84% males, 46 years; hepatitis B virus [HBV] DNA: 6.0 log cp/mL; alanine aminotransferase [ALT]: 136 IU/L; 42% with cirrhosis) were followed up for a median of 11 years (range, 1-17) after a median of 23 months (range, 10-48) of either standard or pegylated (Peg)-IFN-alpha therapy. A post-treatment response was defined as hepatitis B surface antigen (HBsAg) clearance with or without antibody to hepatitis B surface antigen (anti-HBs) seroconversion. The rs12979860 (C>T) genotype in the IL28B locus was assessed in serum samples by using Custom TaqMan SNP Genotyping Assays (Applied Biosystems, Carlsbad, CA). During a median of 11 years of post-treatment follow-up, 21 patients (21%) cleared serum HBsAg, including 15 who developed>10 IU/mL of anti-HBs titers. Forty-eight patients (47%) had CC genotype, 42 (42%) had CT, and 11 (11%) had TT, with the allelic frequency being 68% for C allele and 32% for T allele. The rate of serum HBsAg clearance was 29% (n=14) in CC compared to 13% (n=7) in non-CC, genotype carriers (P=0.039). Baseline HBV DNA levels<6 log cp/mL (odds ratio [OR], 11.9; 95% confidence interval [CI]: 2.8-50.6; P=0.001), ALT levels>136 IU/L (OR, 6.5; 95% CI: 1.8-22.5; P=0.003), duration of IFN (OR, 1.16; 95% CI: 1.02-1.31; P=0.021), and genotype CC (OR, 3.9; 95% CI: 1.1-13.2; P=0.025) independently predicted HBsAg clearance.

Conclusions: IL28B polymorphism is an additional predictor of off-therapy IFN-related HBsAg seroclearance to be used in the pretreatment stratification of HBeAg-negative patients chronically infected by genotype D of HBV.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Drug Resistance, Viral / genetics
  • Female
  • Follow-Up Studies
  • Genetic Testing
  • Genotype
  • Hepacivirus / genetics*
  • Hepacivirus / immunology
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B e Antigens / blood
  • Hepatitis B e Antigens / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / immunology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide / genetics
  • Predictive Value of Tests
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies


  • Antiviral Agents
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • IFNL3 protein, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Interferons
  • peginterferon alfa-2b
  • peginterferon alfa-2a