Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline

Abstract

Serum hepatitis B surface antigen (HBsAg) levels may reflect the immunomodulatory efficacy of pegylated interferon (PEG‐IFN). We investigated within a large randomized trial whether quantitative HBsAg levels predict response to PEG‐IFN in patients with hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B. Serum HBsAg was measured in samples taken at baseline and weeks 4, 8, 12, 24, 52, and 78 of 221 patients treated with PEG‐IFN alfa‐2b with or without lamivudine for 52 weeks. HBsAg decline was compared between treatment arms and between responders and nonresponders. Response was defined as HBeAg loss with HBV DNA < 10,000 copies/mL at 26 weeks after treatment (week 78); 43 of 221 (19%) patients achieved a response. One year of PEG‐IFN with or without lamivudine resulted in a significant decline in serum HBsAg, which was sustained after treatment (decline 0.9 log IU/mL at week 78, P < 0.001). Patients treated with combination therapy experienced a more pronounced on‐treatment decline, but relapsed subsequently. Responders experienced a significantly more pronounced decline in serum HBsAg compared to nonresponders (decline at week 52: 3.3 versus 0.7 log IU/mL, P < 0.001). Patients who achieved no decline at week 12 had a 97% probability of nonresponse through posttreatment follow‐up and no chance of HBsAg loss. In a representative subset of 149 patients similar results were found for prediction through long‐term (mean 3.0 years) follow‐up. Conclusion: PEG‐IFN induces a significant decline in serum HBsAg in HBeAg‐positive patients. Patients who experience no decline from baseline at week 12 have little chance of achieving a sustained response and no chance of HBsAg loss and should be advised to discontinue therapy with PEG‐IFN. (HEPATOLOGY 2010)