Response to peginterferon alfa-2a (40KD) in HBeAg-negative CHB: On-treatment kinetics of HBsAg serum levels vary by HBV genotype

Background & Aims: We investigated whether HBV genotype influences on-treatment HBsAg kinetics and/or the end-of-treatment HBsAg levels associated with long-term virological response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a +/- lamivudine in the Phase III trial. Methods: All patients (n = 230) who participated in long-term follow-up were included according to the availability of HBsAg level measurements. Long-term virological response was defined as HBV DNA <= 10,000 cp/ml (1786 IU/ml) at 5 years post-treatment. Genotype-specific end-of-treatment HBsAg levels associated with long-term virological response (identified by ROC analysis) were assessed in 199 patients with HBsAg measurements available at baseline and end-of-treatment. HBsAg kinetics according to genotype and long-term virological response were investigated in the 117 patients with additional samples available at weeks 12, 24, and 72. Results: Baseline HBsAg levels were significantly higher for A than B, C, and D genotypes (p <0.05). On-treatment HBsAg kinetics varied according to HBV genotype. The difference between responders and non-responders was greatest for genotype A from weeks 12-24; for genotypes B and D from baseline to week 12; there was no significant difference over any timeframe for genotype C. High positive predictive values for long-term virological response could be obtained by applying end-of-treatment genotype-specific cut-offs: 75%, 47%, 71%, and 75% for genotypes A (<400 IU/ml), B (<50 IU/ml), C (<75 IU/ml), and D (<1000 IU/ml), respectively. Conclusions: On-treatment HBsAg kinetics vary between HBV genotypes. Genotype-specific monitoring timeframes and end-of-treatment thresholds could ameliorate response-guided treatment of HBeAg-negative chronic hepatitis B. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.