Commentary: HBsAg levels as predictor of sustained response to peginterferon in HBeAg‐negative chronic hepatitis B – author's reply

Abstract

We are grateful to Professor Hadziyannis for his comment on our study.1, 2 Several issues remain unresolved regarding the predictive role of serum HBsAg level during peginterferon therapy in HBeAg-negative chronic hepatitis B (CHB) patients. First, various definitions of ‘sustained response’, such as HBV DNA <70 copies/mL,3 <400 copies/mL,4 <10 000 copies/mL,5 and HBV DNA <10 000 copies/mL with ALT normalisation at defined time points off peginterferon therapy have been adopted.6 We demonstrated clearly distinct predictive values of the serum HBsAg level at week 12 for different endpoints (Table S7).1 Therefore, the definition of ‘sustained response’ should be uniform to allow comparisons among studies. Secondly, a decline in serum HBsAg level or a cut-off level has been proposed as the criterion to assess response.3-6 We compared systematically the predictive values of HBsAg and HBV DNA levels, a decline in serum HBsAg and HBV DNA levels, and their combinations at week 12 or 24 of therapy for sustained response (HBV DNA <312 copies/mL) and found that the serum HBsAg level at week 12 has the best predictive value (Tables 4 and S4),1 suggesting that the remaining intrahepatic cccDNA level is the more critical determinant of a sustained response than its magnitude of decline. Thirdly, we identified the predictive role of serum HBsAg level at week 12 of therapy in patients infected with genotype B or C. The stopping rule proposed by Rijckborst et al.6 did not perform well in our cohort. Brunetto et al.5 proposed genotype-specific cut-offs at the end of 48-week therapy for predicting a sustained response at 5 years post-treatment. Together, these support the need of genotype-specific algorithms in future clinical application. We concur we had a small sample size. A large, multicentre, genotype-stratified study is warranted to establish a genotype-specific prediction rule for HBeAg-negative CHB patients undergoing peginterferon therapy. Declaration of personal interests: Cheng-Yuan Peng has acted as a consultant for Roche, Bristol-Myers Squibb and Novartis. Declaration of funding interests: None.