Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen levels


  • Potential conflict of interest: Milan J. Sonneveld consults and is on the speakers' bureau for Roche. Bettina Hansen has nothing to disclose. Henry L.Y. Chan advises, is on the speakers' bureau for, and received grants from Roche. He advises and is on the speakers' bureau for Abbott, Bristol-Myers Squibb, Gilead, Novartis, and MSD. Teerha Piratvisuth advises, received grants from, and is on the speakers' bureau for Roche and Novartis. He advises and is on the speakers' bureau for MSD. He is on the speakers' bureau and received grants from Bristol-Myers Squibb. He is also on the speakers' bureau for GlaxoSmithKline. Ji-Dong Jia consults and is on the speakers' bureau for MBS, Novartis, and Roche. Stefan Zeuzem consults, advises, and is on the speakers' bureau for Roche and Merck. Edward Gane advises and is on the speakers' bureau for Roche and Gilead. He advises Janssen and is on the speakers' bureau for Abbott. Y.F. Liaw was involved in clinical trials or served as a global advisory board member of Roche, Bristol-Myers Squibb, Novartis and Gilead Sciences. Harry L.A. Janssen received grants from and is a consultant for Bristol-Myers Squibb, Gilead Sciences, Novartis, Roche, Merck and Innogenetics. E.J. Heathcote is a consultant of Gilead Sciences and received research support from Gilead Sciences, Hoffman-La Roche, Merck, Tibotec, and Vertex.

  • Supported by the Foundation for Liver and Gastrointestinal Research (SLO) in Rotterdam, the Netherlands. The funding source did not have influence on study design, data collection, analysis, or interpretation of the data, writing of the report nor the decision to submit for publication.

Address reprint requests to: Prof. H.L.A. Janssen, M.D., Ph.D., Division of Gastroenterology, Toronto Western Hospital, University Health Network, 399 Bathurst St., 6B FP, Room 164, Toronto, ON, M5T 2S8 Canada. E-mail:; fax: 416-603-6281.


On-treatment levels of hepatitis B surface antigen (HBsAg) may predict response to peginterferon (PEG-IFN) therapy in chronic hepatitis B (CHB), but previously proposed prediction rules have shown limited external validity. We analyzed 803 HBeAg-positive patients treated with PEG-IFN in three global studies with available HBsAg measurements. A stopping-rule based on absence of a decline from baseline was compared to a prediction-rule that uses HBsAg levels of <1,500 IU/mL and >20,000 IU/mL to identify patients with high and low probabilities of response. Patients with an HBsAg level <1,500 IU/mL at week 12 achieved response (HBeAg loss with HBV DNA <2,000 IU/mL at 6 months posttreatment) in 45%. At week 12, patients without a decline in HBsAg achieved a response in 14%, compared to only 6% of patients with HBsAg >20,000 IU/mL, but performance varied across HBV genotype. In patients treated with PEG-IFN monotherapy (n = 465), response rates were low in patients with genotypes A or D if there was no decline of HBsAg by week 12 (negative predictive value [NPV]: 97%-100%), and in patients with genotypes B or C if HBsAg at week 12 was >20,000 IU/mL (NPV: 92%-98%). At week 24, nearly all patients with HBsAg >20,000 IU/mL failed to achieve a response, irrespective of HBV genotype (NPV for response and HBsAg loss 99% and 100%). Conclusion: HBsAg is a strong predictor of response to PEG-IFN in HBeAg-positive CHB. HBV genotype-specific stopping-rules may be considered at week 12, but treatment discontinuation is indicated in all patients with HBsAg >20,000 IU/mL at week 24, irrespective of HBV genotype. (Hepatology 2013;53:872–880)