P Hu1, J Shang2, W H Zhang3, G Z Gong4, Y G Li5, X Y Chen6, J N Jiang7, Q Xie8, X G Dou9, Y T Sun10, Y F Li11, Y X Liu12, G Z Liu13, D W Ma14, X L Chi15, H Tang16, X O Li17, Y Xie18, X P Chen19, J J Jiang20, P Zha21, J L Hou22, Z L Gao23, H M Fan24, J G Ding25, D Z Zhang1, H Ren1. 1. Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. 2. Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou 450003, China. 3. Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. 4. Department of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha 410011, China. 5. Department of Infectious Diseases, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. 6. International Medical Department, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China. 7. Department of Infectious Diseases, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China. 8. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. 9. Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110004, China. 10. Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China. 11. Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan 750004, China. 12. Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen 518035, China. 13. Department of Infectious Diseases, Xiangya Hospital Central South University, Changsha 410008, China. 14. Liver Disease Department, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China. 15. Liver Disease Department, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou 510120, China. 16. Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China. 17. Liver Disease Department, The Sixth People's Hospital of Hangzhou, Hangzhou 310007, China. 18. Liver Disease Department, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China. 19. Department of Infectious Diseases, Guangdong General Hospital, Guangzhou 510010, China. 20. Center of Liver Diseases, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China. 21. International Center for Liver Disease Treatment, 302 Hospital of PLA, Beijing 100039, China. 22. Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. 23. Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China. 24. Hepatology Unit, Guangzhou Eighth People's Hospital, Guangzhou 510060, China. 25. Hepatology Unit, Ruian People's Hospital, Ruian 325200, China.
Abstract
Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.
RCT Entities:
Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis Bpatients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis Bpatients with partial response to a previous NA. Methods:Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.