Durable hepatitis B surface antigen decline in hepatitis B e antigen-positive chronic hepatitis B patients treated with pegylated interferon-α2b: relation to response and HBV genotype

Background: On-treatment decline of serum hepatitis B surface antigen (HBsAg) may reflect the immunomodulatory effect of pegylated interferon (PEG-IFN) for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). We compared HBsAg decline across HBV genotypes between combined responders (HBeAg loss and HBV DNA < 10,000 copies/ml at week 78), HBeAg responders (HBeAg loss with HBV DNA > 10,000 copies/ml) and non-responders. Methods: HBsAg was measured at baseline, on-treatment and 6 months post-treatment in 221 HBeAg-positive CHB patients treated with PEG-IFN with or without lamivudine for 52 weeks, and in a representative subgroup of 142 patients at long-term follow-up (LTFU; mean 3.0 years). Results: On-treatment HBsAg decline significantly varied according to HBV genotype (A and B more than C and D; P < 0.001). On-treatment HBsAg decline also differed between patients with a combined response (n = 43) and those without (n = 178; 3.34 versus 0.69 log IU/ml decline at week 52; P < 0.001). Among patients without a combined response, no difference was observed between HBeAg responders (n = 41) versus non-responders (n = 137). HBsAg decline was sustained in combined responders and progressed to 3.75 log IU/ml at LTFU. Patients with a combined response achieved pronounced HBsAg declines, irrespective of HBV genotype, and those who achieved HBsAg levels < 1,000 IU/ml at week 78 had a high probability of a sustained response and HBsAg clearance through LTFU. Conclusions: On-treatment HBsAg decline during PEG-IFN therapy for HBeAg-positive CHB depends upon HBV genotype. Patients with a combined response to PEG-IFN achieve a pronounced HBsAg decline, irrespective of HBV genotype, which is sustained through 3 years of off-treatment follow-up.