Hepatitis B virus surface antigen levels: A guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B


  • See Editorial on Page 1063

  • Potential conflict of interest: Dr. Brunetto is on the speakers' bureau of Roche. Dr. Bonino is a consultant for, advises, and is on the speakers' bureau of Abbott, Bristol-Myers Squibb, Gilead, and Novartis. He is also in the speakers' bureau of Schering-Plough. Dr. Lau is on the speakers' bureau of and received grants from Roche and Novartis. Dr. Piratvisuth advises and is on the speakers' bureau of Roche. He advises Novartis and Schering-Plough and is on the speaker's bureau of GlaxoSmith Kline. Dr. Hadziyannis is on the speakers' bureau of and received grants from Roche. He advises and received grants from Gilead. He advises Novartis and Bristol-Myers Squibb. Dr. McCloud owns stock in Roche.


We investigated the relationship between hepatitis B virus surface antigen (HBsAg) serum level decline and posttreatment response in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B from a large multinational study of pegylated interferon alfa-2a (peginterferon alfa-2a), with or without lamivudine, versus lamivudine alone. Serum HBsAg was quantified using the Architect assay (Abbott Diagnostics) at pretreatment, end of treatment (week 48), and 6 months after the end of treatment (week 72) in sera from 386 of the 537 patients who participated in the multinational study (peginterferon alfa-2a, 127; peginterferon alfa-2a plus lamivudine, 137; lamivudine monotherapy, 122). Pretreatment HBsAg levels varied according to genotype, with the highest levels present in patients infected with genotypes A (median, 4.11 log10 IU/mL) and D (median, 3.85 log10 IU/mL). Significant on-treatment decline in HBsAg was observed during treatment with peginterferon alfa-2a (alone or combined with lamivudine; mean decline at week 48, −0.71 and −0.67 log10 IU/mL, respectively, P < 0.001), but not during treatment with lamivudine alone (−0.02 log10 IU/mL). Significantly more patients treated with peginterferon alfa-2a (21%) or peginterferon alfa-2a plus lamivudine (17%) achieved HBsAg levels <100 IU/mL at the end of treatment compared with lamivudine (1%) (both P < 0.001 versus lamivudine). End-of-treatment HBsAg level correlated strongly with HBV DNA suppression to ≤400 copies/mL 6 months posttreatment. An HBsAg level <10 IU/mL at week 48 and on-treatment decline >1 log10 IU/mL were significantly associated with sustained HBsAg clearance 3 years after treatment (both P < 0.0001). Conclusion: On-treatment quantification of HBsAg in patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a may help identify those likely to be cured by this therapy and optimize treatment strategies. (HEPATOLOGY 2009;49:1141–1150.)