Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients
Tung-Hung Su
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Search for more papers by this authorTsung-Hui Hu
Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorChi-Yi Chen
Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan
Search for more papers by this authorYi-Hsiang Huang
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
Search for more papers by this authorWan-Long Chuang
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorChun-Che Lin
Division of Gastroenterology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
Search for more papers by this authorChia-Chi Wang
Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, the Buddhist Tzuchi Medical Foundation, Taipei, Taiwan
Search for more papers by this authorWei-Wen Su
Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
Search for more papers by this authorMing-Yao Chen
Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorCheng-Yuan Peng
Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Search for more papers by this authorRong-Nan Chien
Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan
Search for more papers by this authorYi-Wen Huang
Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan
Search for more papers by this authorHorng-Yuan Wang
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
Search for more papers by this authorChih-Lin Lin
Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan
Search for more papers by this authorSheng-Shun Yang
Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
Search for more papers by this authorTsung-Ming Chen
Division of Hepato-Gastroenterology, Department of Internal Medicine and Department of Medical Research, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan
Search for more papers by this authorLein-Ray Mo
Department of Internal Medicine, Tainan Municipal Hospital, Tainan, Taiwan
Search for more papers by this authorShih-Jer Hsu
Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
Search for more papers by this authorKuo-Chih Tseng
Department of Hepatology, Buddhist Tzu Chi General Hospital, Da-Lin Branch, Chiayi, Taiwan
Search for more papers by this authorTsai-Yuan Hsieh
Department of Gastroenterology, Tri-service General Hospital, Taipei, Taiwan
Search for more papers by this authorFat-Moon Suk
Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorChi-Tan Hu
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital and University, Hualien, Taiwan
Search for more papers by this authorMing-Jong Bair
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung, Taiwan
Search for more papers by this authorCheng-Chao Liang
Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan
Search for more papers by this authorYung-Chao Lei
Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorTai-Chung Tseng
Department of Internal Medicine, National Taiwan University Hospital, Jin-Shan Branch, New Taipei City, Taiwan
Search for more papers by this authorChi-Ling Chen
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Search for more papers by this authorCorresponding Author
Jia-Horng Kao
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Correspondence
Jia-Horng Kao MD, PhD, FAASLD, National Chair Professor, Ministry of Education, and Distinguished Professor, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Email: [email protected]
Search for more papers by this authorthe C-TEAM study group and the Taiwan Liver Diseases Consortium
Search for more papers by this authorTung-Hung Su
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Search for more papers by this authorTsung-Hui Hu
Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Search for more papers by this authorChi-Yi Chen
Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan
Search for more papers by this authorYi-Hsiang Huang
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
Search for more papers by this authorWan-Long Chuang
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorChun-Che Lin
Division of Gastroenterology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
Search for more papers by this authorChia-Chi Wang
Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, the Buddhist Tzuchi Medical Foundation, Taipei, Taiwan
Search for more papers by this authorWei-Wen Su
Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
Search for more papers by this authorMing-Yao Chen
Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorCheng-Yuan Peng
Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Search for more papers by this authorRong-Nan Chien
Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan
Search for more papers by this authorYi-Wen Huang
Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan
Search for more papers by this authorHorng-Yuan Wang
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
Search for more papers by this authorChih-Lin Lin
Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan
Search for more papers by this authorSheng-Shun Yang
Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
Search for more papers by this authorTsung-Ming Chen
Division of Hepato-Gastroenterology, Department of Internal Medicine and Department of Medical Research, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan
Search for more papers by this authorLein-Ray Mo
Department of Internal Medicine, Tainan Municipal Hospital, Tainan, Taiwan
Search for more papers by this authorShih-Jer Hsu
Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
Search for more papers by this authorKuo-Chih Tseng
Department of Hepatology, Buddhist Tzu Chi General Hospital, Da-Lin Branch, Chiayi, Taiwan
Search for more papers by this authorTsai-Yuan Hsieh
Department of Gastroenterology, Tri-service General Hospital, Taipei, Taiwan
Search for more papers by this authorFat-Moon Suk
Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorChi-Tan Hu
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital and University, Hualien, Taiwan
Search for more papers by this authorMing-Jong Bair
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung, Taiwan
Search for more papers by this authorCheng-Chao Liang
Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan
Search for more papers by this authorYung-Chao Lei
Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorTai-Chung Tseng
Department of Internal Medicine, National Taiwan University Hospital, Jin-Shan Branch, New Taipei City, Taiwan
Search for more papers by this authorChi-Ling Chen
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Search for more papers by this authorCorresponding Author
Jia-Horng Kao
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Correspondence
Jia-Horng Kao MD, PhD, FAASLD, National Chair Professor, Ministry of Education, and Distinguished Professor, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Email: [email protected]
Search for more papers by this authorthe C-TEAM study group and the Taiwan Liver Diseases Consortium
Search for more papers by this authorAbstract
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.
Supporting Information
Additional Supporting Information may be found online in the supporting information tab for this article.
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