BACKGROUND AND AIM: IL28B genotype predicts response to pegylated interferon (peg-IFN)-based therapy in chronic hepatitis C. However, the utility of IL28B genotyping in chronic hepatitis B (CHB) cohorts treated with peg-IFN is unclear. It was investigated whether IL28B genotype is associated with peg-IFN treatment outcomes in a predominantly Asian CHB cohort. METHODS: This was a retrospective analysis of CHB patients treated with 48 weeks of peg-IFN monotherapy. IL28B genotype (rs12979860) was determined (TaqMan allelic discrimination kit). Baseline hepatitis B virus (HBV)-DNA, alanine aminotransferase, and liver histology were available. The primary end-points were HBV e antigen (HBeAg) seroconversion with HBV-DNA <2000 IU/mL 24 weeks post-therapy (HBeAg-positive patients) and HBV-DNA <2000 IU/mL 24 weeks after peg-IFN (HBeAg-negative patients). The association between IL28B genotype and peg-IFN outcomes was analyzed. RESULTS: IL28B genotype was determined for 96 patients. Eighty-eight percent were Asian, 62 were HBeAg positive, and 13 were METAVIR stage F3-4. Median follow-up time was 39.3 months. The majority of patients carried the CC IL28B genotype (84 ). IL28B genotype did not differ according to HBeAg status. The primary end-points were achieved in 27 of HBeAg-positive and 61 of HBeAg-negative patients. There was no association between IL28B genotype and the primary end-point in either group. Furthermore, there was no difference in HBeAg loss alone, HBV surface antigen, alanine aminotransferase normalization, or on-treatment HBV-DNA levels according to IL28B genotype. CONCLUSIONS: In the context of a small possible effect size and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asia-Pacific region.