IL28B Genotype is Not Useful for Predicting Treatment Outcome in Asian Chronic Hepatitis B Patients Treated with Pegylated-interferon-?

Holmes JA, Nguyen T, Ratnam D, Heerasing NM, Tehan JV, Bonanzinga S, Dev A, Bell S, Pianko S, Chen R, Visvanathan K, Hammond R, Iser D, Rusli F, Sievert W, Desmond PV, Bowden DS, Thompson AJ

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. We 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 HBV DNA, ALT, and liver histology were available. The primary endpoints were HBeAg seroconversion with HBV DNA<2,000 IU/mL 24-weeks post-therapy (HBeAg-positive patients), and HBV DNA<2,000 IU/mL 24-weeks after peg-IFN (HBeAg-negative patients). We analysed the association between IL28B genotype and peg-IFN outcomes.

RESULTS: IL28B genotype was determined for 96 patients. 88% 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 endpoints were achieved in 27% of HBeAg-positive and 61% of HBeAg-negative patients. There was no association between IL28B genotype and the primary endpoint in either group. Furthermore, there was no difference in HBeAg loss alone, HBsAg loss, ALT normalisation 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 Asian-Pacific region.