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IL28B polymorphism predictive of surface antigen seroclearance in chronic HBV patients

The outcome of interferon-based therapy for chronic hepatitis B is impacted by IL28B polymorphism, according to recent data.

Researchers evaluated 101 hepatitis B e antigen-negative (HBeAg-negative) patients with compensated chronic hepatitis B treated with standard or pegylated interferon-alfa for a median of 23 months. Most participants (92%) were infected with genotype D. IL28B genotyping was performed and hepatitis B surface antigen (HBsAg) clearance was assessed during a median follow-up of 11 years. Forty-seven percent of the cohort had genotype CC at the IL28B locus, with 42% having CT and 11% TT. Allelic frequency was 68% for C and 32% for T across the cohort.

End-of-treatment response and sustained virologic response (SVR) occurred more frequently among patients with CC genotype than those without (69% vs. 45%; P=.014 for end-of-treatment response; 31% vs. 13%; P=.025 for SVR).During follow-up, HBsAg seroclearance occurred in 21% of cases, including 15 patients with anti-HBs titers greater than 10 IU/mL. Patients with CC genotype achieved HBsAg clearance in 29% of cases compared with 13% of patients without CC genotype (P=.039 for difference).

Factors independently predictive of clearance via multivariate analysis included baseline HBV DNA levels below 6 log cp/mL (OR=11.9; 95% CI, 2.8-50.6), ALT levels above 136 IU/L (OR=6.5; 95% CI, 1.8-22.5), genotype CC (OR=3.9; 95% CI, 1.1-13.2) and interferon (IFN) treatment duration (OR=1.16; 95% CI, 1.02-1.31). HBV DNA and genotype CC were predictive of end-of-treatment response and SVR, while treatment duration also predicted end-of-treatment response, and age independently predicted SVR.

“Our findings indicate that the IL28B polymorphism is a reliable predictor of IFN therapy outcome in HBV, which might be used for pretreatment stratification aimed at optimizing the treatment of such a difficult-to-cure patient population as HBeAg-negative carriers of genotype D of HBV,” the researchers concluded. “Optimization of IFN treatment of HBeAg-negative patients with CHB … might help in overcoming such barriers to treatment as the need for parenteral administration, limited effectiveness and poor tolerability.”

Disclosure: See the study for a full list of relevant disclosures.