Tung-Hung Su1,2, Tsung-Hui Hu3, Chi-Yi Chen4, Yi-Hsiang Huang5,6, Wan-Long Chuang7, Chun-Che Lin8, Chia-Chi Wang9, Wei-Wen Su10, Ming-Yao Chen11, Cheng-Yuan Peng12, Rong-Nan Chien13, Yi-Wen Huang14, Horng-Yuan Wang15, Chih-Lin Lin16, Sheng-Shun Yang17, Tsung-Ming Chen18, Lein-Ray Mo19, Shih-Jer Hsu20, Kuo-Chih Tseng21, Tsai-Yuan Hsieh22, Fat-Moon Suk23, Chi-Tan Hu24, Ming-Jong Bair25, Cheng-Chao Liang26, Yung-Chao Lei27, Tai-Chung Tseng28, Chi-Ling Chen2, Jia-Horng Kao1,2. 1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 2. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 3. Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 4. Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan. 5. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 6. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 7. Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 8. Division of Gastroenterology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan. 9. Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, the Buddhist Tzuchi Medical Foundation, Taipei, Taiwan. 10. Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan. 11. Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan. 12. Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. 13. Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan. 14. Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan. 15. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. 16. Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan. 17. Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. 18. Division of Hepato-Gastroenterology, Department of Internal Medicine and Department of Medical Research, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan. 19. Department of Internal Medicine, Tainan Municipal Hospital, Tainan, Taiwan. 20. Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan. 21. Department of Hepatology, Buddhist Tzu Chi General Hospital, Da-Lin Branch, Chiayi, Taiwan. 22. Department of Gastroenterology, Tri-service General Hospital, Taipei, Taiwan. 23. Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 24. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital and University, Hualien, Taiwan. 25. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung, Taiwan. 26. Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan. 27. Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan. 28. Department of Internal Medicine, National Taiwan University Hospital, Jin-Shan Branch, New Taipei City, Taiwan.
Abstract
BACKGROUND & AIMS: Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB-related cirrhosis patients. METHODS: The C-TEAM (Cirrhosis-Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective-prospective cohort study in Taiwan. We enrolled treatment-naïve patients with CHB-related cirrhosis and baseline HBV-DNA≥2000 IU/mL receiving long-term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort. RESULTS: In total, 1315 entecavir-treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow-up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction [hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28-0.57]. Additionally, an older age, the male gender, HBeAg positivity, alpha-fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver-related and all-cause mortality. These findings were confirmed by propensity score-matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1-year virological response were predictive of HCC development. CONCLUSIONS: Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.
BACKGROUND & AIMS: Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB-related cirrhosispatients. METHODS: The C-TEAM (Cirrhosis-Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective-prospective cohort study in Taiwan. We enrolled treatment-naïve patients with CHB-related cirrhosis and baseline HBV-DNA≥2000 IU/mL receiving long-term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort. RESULTS: In total, 1315 entecavir-treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow-up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction [hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28-0.57]. Additionally, an older age, the male gender, HBeAg positivity, alpha-fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver-related and all-cause mortality. These findings were confirmed by propensity score-matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1-year virological response were predictive of HCC development. CONCLUSIONS: Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.
Authors: Anna S Lok; Robert Perrillo; Christina M Lalama; Michael W Fried; Steven H Belle; Marc G Ghany; Mandana Khalili; Robert J Fontana; Richard K Sterling; Norah Terrault; Jordan J Feld; Adrian M Di Bisceglie; Daryl T Y Lau; Mohamed Hassan; Harry L A Janssen Journal: Hepatology Date: 2021-05-21 Impact factor: 17.425