Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B

BACKGROUND: Various treatment combinations of peginterferon (PEG-IFN) and nucleos(t)ide analogues have been evaluated for chronic hepatitis B (CHB), but the optimal regimen remains unclear. AIMS: To study whether PEG-IFN add-on increases response compared to entecavir (ETV) monotherapy, and whether the duration of ETV pretreatment influences response. METHODS: Response was evaluated in HBeAg positive patients previously treated in two randomized controlled trials. Patients received ETV pretreatment for at least 24 weeks and were then allocated to 24-48 weeks of ETV+PEG-IFN add-on, or continued ETV monotherapy. Response was defined as HBeAg loss combined with HBV DNA <200 IU/mL 48 weeks after discontinuing PEG-IFN. RESULTS: Of 234 patients, 118 were assigned PEG-IFN add-on and 116 continued ETV monotherapy. Response was observed in 38/118 (33%) patients treated with add-on therapy and in 23/116 (20%) with monotherapy (P = 0.03). The highest response to add-on therapy compared to monotherapy was observed in PEG-IFN naive patients with HBsAg levels below 4000 IU/mL and HBV DNA levels below 50 IU/mL at randomization (70% vs 34%; P = 0.01). Above the cut-off levels, response was low and not significantly different between treatment groups. Duration of ETV pretreatment was associated with HBsAg and HBV DNA levels (both P < 0.005), but not with response (P = 0.82). CONCLUSIONS: PEG-IFN add-on to ETV therapy was associated with higher response compared to ETV monotherapy in patients with HBeAg positive CHB. Response doubled in PEG-IFN naive patients with HBsAg below 4000 IU/mL and HBV DNA below 50 IU/mL, and therefore identifies them as the best candidates for PEG-IFN add-on (Identifiers: NCT00877760, NCT01532843).