Polymorphisms Near IL28B and Serologic Response to Peginterferon in HBeAg-Positive Patients With Chronic Hepatitis B

BACKGROUND & AIMS: A limited number of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B respond to treatment with peginterferon alfa (PEG-IFN). We investigated whether IL28B genotypes are associated with response. METHODS: We studied 205 HBeAg-positive patients who were treated with PEG-IFN (some were also treated with lamivudine) at 11 European and Asian hospitals; genotype analysis was performed for IL28B rs12980275 and rs12979860. Response was defined as HBeAg loss with the appearance of antibodies to hepatitis B e antigen (anti-HBe) at the end of PEG-IFN therapy (HBeAg seroconversion), along with HBeAg seroconversion and hepatitis B surface antigen clearance during long-term follow-up. RESULTS: The patients were infected with hepatitis B virus (HBV) genotypes A (13%), B (20%), C (47%), and D (13%). The proportions of IL28B genotypes were 77%, 19%, and 5% for AA/AG/GG at rs12980275 and also for CC/CT/TT at rs12979860, respectively. IL28B genotype was significantly associated with HBeAg seroconversion at the end of treatment (P < .001); the adjusted odds ratio for seroconversion was 3.16 (95% confidence interval [CI], 1.26 - 8.52; P = .013) for AA versus AG/GG at rs12980275 after adjustment for HBV genotype, age, levels of HBV DNA and alanine aminotransferase, and combination therapy. IL28B genotype was independently associated with an increased probability of HBeAg seroconversion during long-term follow-up (adjusted hazard ratio [HR], 2.14; 95% CI, 1.14 - 4.31; P = .018 for AA vs AG/GG by Cox regression analysis). Similar results were obtained for rs12979860. IL28B genotype was also associated with hepatitis B surface antigen clearance (HR, 3.47 for AA vs AG/GG; 95% CI, 1.04 - 13.48; P = .042). CONCLUSIONS: Polymorphisms near IL28B are independently associated with serologic response to PEG-IFN in patients with HBeAg-positive chronic hepatitis B.