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Article first published online: 25 APR 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 1, pages 67–75, July 2012
How to Cite
Sonneveld, M. J., Rijckborst, V., Zeuzem, S., Heathcote, E. J., Simon, K., Senturk, H., Pas, S. D., Hansen, B. E. and Janssen, H. L.A. (2012), Presence of precore and core promoter mutants limits the probability of response to peginterferon in hepatitis B e antigen-positive chronic hepatitis B. Hepatology, 56: 67–75. doi: 10.1002/hep.25636
Potential conflicts of interest: Milan J. Sonneveld, Krzysztof Simon, Hakan Senturk, Suzan Pas, and Bettina E. Hansen have nothing to disclose. Prof.dr. H.L.A. Janssen received grants from and is a consultant for: Bristol Myers Squibb, Gilead Sciences, Novartis, Roche, Merck, Innogenetics. Vincent Rijckborst is a consultant for Roche. Stefan Zeuzem is a consultant for: BMS, Biolex, HGS, Merck/Schering-Plough, Novartis, and Roche. E. Jenny Heathcote received funds for research and fees for consulting from Roche and Gilead Sciences.
Study initiator and sponsor: Foundation for Liver Research (SLO), Rotterdam, the Netherlands.
- Issue published online: 3 JUL 2012
- Article first published online: 25 APR 2012
- Accepted manuscript online: 6 FEB 2012 12:06AM EST
- Manuscript Accepted: 24 JAN 2012
- Manuscript Received: 9 AUG 2011
Peginterferon (PEG-IFN) treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) results in HBeAg loss in 30% of patients, but clearance of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) from serum is less often achieved. We investigated whether the presence of precore (PC) and basal core promoter (BCP) mutants before PEG-IFN treatment affects serological and virological response. A total of 214 HBeAg-positive CHB patients treated with PEG-IFN±lamivudine for 52 weeks in a global randomized trial were classified at baseline as wildtype (WT) or non-WT (detectable mutants at PC/BCP) by line-probe assay. Response was assessed at 6 months posttreatment and through long-term follow-up (LTFU). Mutants were detected in 64% of patients, in varying frequencies across HBV genotypes A through D. Patients with WT had higher baseline HBV DNA, HBeAg, and HBsAg levels than patients with non-WT. Patients with WT were more likely to achieve HBeAg loss with HBV DNA <10,000 copies/mL (response, 34 versus 11%, P < 0.001) and HBsAg clearance (18 versus 2%, P < 0.001) at week 78 than non-WT patients. Among WT patients who achieved HBeAg clearance at week 78, 78% had undetectable HBV DNA and 61% achieved HBsAg clearance at LTFU (versus 26% and 15% in non-WT patients, P < 0.001 for both). The presence of WT virus at baseline was an independent predictor of response (odds ratio [OR] 2.90, 95% confidence interval [CI]: 1.15-7.31, P = 0.023) and HBsAg clearance (OR 5.58, 95% CI: 1.26-24.63, P = 0.013) and patients with non-A genotypes with detectable mutants had a low probability of response. Conclusion: The presence of only WT virus at baseline is a strong predictor of response (HBeAg loss with HBV DNA <10,000 copies/mL) to PEG-IFN for HBeAg-positive CHB. Patients with detectable PC and/or BCP mutants have a lower probability of response and are less optimal candidates for PEG-IFN therapy. (HEPATOLOGY 2012;56:67–75)