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 HBeAgpositive 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.

Additional Metadata
Keywords Hepatitis B virus, adult, article, blood level, chronic patient, controlled study, disease severity, drug dose reduction, female, follow up, genotype, hepatitis B, human, long term care, long term follow up, major clinical study, male, priority journal, probability, treatment duration, treatment outcome, treatment response, virotherapy
Persistent URL dx.doi.org/10.3851/IMP1887, hdl.handle.net/1765/39205
Journal Antiviral Therapy
Citation
Sonneveld, M.J, Rijckborst, V, Cakaloglu, Y, Simon, K, Heathcote, E.J, Tabak, F, … Janssen, H.L.A. (2012). 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. Antiviral Therapy, 17(1), 9–17. doi:10.3851/IMP1887