Jin-Lin Hou1, Wei Zhao2, Changhyeong Lee3, Hie-Won Hann4, Cheng-Yuan Peng5, Tawesak Tanwandee6, Viacheslav Morozov7, Hartwig Klinker8, Jose D Sollano9, Adrian Streinu-Cercel10, Hugo Cheinquer11, Qing Xie12, Yu-Ming Wang13, Lai Wei14, Ji-Dong Jia15, Guozhong Gong16, Kwang-Hyub Han17, Wukui Cao18, Mingliang Cheng19, Xiaoping Tang20, Deming Tan21, Hong Ren22, Zhongping Duan23, Hong Tang24, Zhiliang Gao25, Shijun Chen26, Shumei Lin27, Jifang Sheng28, Chengwei Chen29, Jia Shang30, Tao Han31, Yanyan Ji32, Junqi Niu33, Jian Sun34, Yongpeng Chen34, Elizabeth L Cooney35, Seng-Gee Lim36. 1. Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: jlhousmu@163.com. 2. Department of Infectious Diseases, 2nd Hospital Nanjing, Nanjing, China. 3. Daegu Catholic University Hospital, Daegu, Korea. 4. Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. 5. Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. 6. Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. 7. LLC Medical Company "Hepatolog," Samara, Russian Federation. 8. Department of Medicine II, Division of Hepatology, University of Würzburg Medical Center, Würzberg, Germany. 9. Department of Medicine, Cardinal Santos Medical Center, Manila, Philippines. 10. Department of Infectious Diseases I, Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases, "Prof. Dr. Matei Bals," Bucharest, Romania. 11. Gastroenterology and Hepatology Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. 12. Department of Infectious Diseases, Shanghai Rui Jin Hospital, Shanghai, China. 13. Institute for Infectious Diseases, Southwest Hospital, Chongqing, China. 14. Hepatology Department, Peking University People's Hospital, Beijing, China. 15. National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capitol Medical University, Beijing, China. 16. Department of Infectious Disease, The Second Xiangya Hospital of Central South University, Changsha, China. 17. Department of Internal Medicine, Institute of Gastroenterology and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. 18. Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin, China. 19. Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang, China. 20. Department of Infectious Diseases, Guangzhou No. 8 People's Hospital, Guangzhou, China. 21. Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China. 22. Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. 23. Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China. 24. Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China. 25. Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. 26. Hepatology Department, Jinan Infectious Disease Hospital, Jinan, China. 27. Department of Infectious Diseases, The First Affiliated Hospital of Xi'An Jiaotong University, Xi'An, China. 28. Department of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. 29. Hepatology Department, 85th Hospital of People's Liberation Army, Shanghai, China. 30. Department of Infectious Diseases, Henan Provincial People's hospital, Zhengzhou, China. 31. Department of Hepatology and Gastroenterology, Tianjin Third Central Hospital, Tianjin, China. 32. Hepatology Department, Shanghai Jing'an District Central Hospital, Shanghai, China. 33. Hepatobiliary Medical Ward, The First Hospital of Jilin University, Changchun, China. 34. Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China. 35. Bristol-Myers Squibb, Inc, Wallingford, Connecticut. 36. Division of Gastroenterology and Hepatology, National University Health System, National University of Singapore, Singapore.
Abstract
BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analoguefor up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS:Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.
RCT Entities:
BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS:Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.
Authors: Alnoor Ramji; Karen Doucette; Curtis Cooper; Gerald Yosel Minuk; Mang Ma; Alexander Wong; David Wong; Edward Tam; Brian Conway; David Truong; Philip Wong; Lisa Barrett; Hin Hin Ko; Sarah Haylock-Jacobs; Nishi Patel; Gilaad G Kaplan; Scott Fung; Carla S Coffin Journal: World J Gastroenterol Date: 2022-08-21 Impact factor: 5.374
Authors: Sung Won Lee; Jung Hyun Kwon; Hae Lim Lee; Sun Hong Yoo; Hee Chul Nam; Pil Soo Sung; Soon Woo Nam; Si Hyun Bae; Jong Young Choi; Seung Kew Yoon; Nam Ik Han; Jeong Won Jang Journal: Gut Date: 2019-10-31 Impact factor: 23.059