Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels

Peginterferon alfa-2a results in a sustained response (SR) in a minority of patients with hepathis B e antigen (HBeAg) negative chronic hepatitis B (CHB). This study investigated the role of early on-treatment serum hepatitis B surface antigen (HBsAg) levels in the prediction of SR in HBeAg-negative patients receiving peginterferon alfa-2a. HBsAg (Architect from Abbott) was quantified at the baseline and during treatment (weeks 4, 8, 12, 24, 36, and 48) and follow-up (weeks 60 and 72) in the sera from 107 patients who participated in an international multicenter trial (peginterferon alfa-2a, n = 53, versus peginterferon alfa-2a and ribavirin, n = 54). Overall, 24 patients (22%) achieved SR [serum hepatitis B virus (HBV) DNA level < 10,000 copies/mL and normal alanine aminotransferase levels at week 72]. Baseline characteristics were comparable between sustained responders and nonresponders. From week 8 onward, serum HBsAg levels markedly decreased in sustained responders, whereas only a modest decline was observed in nonresponders. However, HBsAg declines alone were of limited value in the prediction of SR [area under the receiver operating characteristic curve (AUC) at weeks 4, 8, and 12 = 0.59, 0.56, and 0.69, respectively]. Combining the declines in HBsAg and HBV DNA allowed the best prediction of SR (AUC at week 12 = 0.74). None of the 20 patients (20% of the study population) in whom a decrease in serum HBsAg levels was absent and whose HBV DNA levels declined less than 2 log copies/mL exhibited an SR (negative predictive value = 100%). Conclusion: At week 12 of peginterferon alfa-2a treatment for HBeAg-negative CHB, a solid stopping rule was established with a combination of declines in serum HBV DNA and HBsAg levels from the baseline. Quantitative serum HBsAg in combination with HBV DNA enables on-treatment adjustments of peginterferon therapy for HBeAg-negative CHB. (HEPATOLOGY 2010;52:454-461)