Source Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

BACKGROUND & AIMS: A limited number of HBeAg-positive patients with 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 anti-HBe at the end of PEG-IFN therapy (HBeAg seroconversion), along with HBeAg seroconversion and HBsAg 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 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 vs 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 HBsAg 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 serological response to PEG-IFN in HBeAg-positive patients with chronic hepatitis B.