title: Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Tung-Hung
authors.initials: TH
authors.lastname: Su
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.affiliation: Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan.
authors.forename: Chi-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Che
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, the Buddhist Tzuchi Medical Foundation, Taipei, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Su
authors.affiliation: Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Yao
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Chien
authors.affiliation: Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Horng-Yuan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Chih-Lin
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Sheng-Shun
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Division of Hepato-Gastroenterology, Department of Internal Medicine and Department of Medical Research, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
authors.forename: Tsung-Ming
authors.initials: TM
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Tainan Municipal Hospital, Tainan, Taiwan.
authors.forename: Lein-Ray
authors.initials: LR
authors.lastname: Mo
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan.
authors.forename: Shih-Jer
authors.initials: SJ
authors.lastname: Hsu
authors.affiliation: Department of Hepatology, Buddhist Tzu Chi General Hospital, Da-Lin Branch, Chiayi, Taiwan.
authors.forename: Kuo-Chih
authors.initials: KC
authors.lastname: Tseng
authors.affiliation: Department of Gastroenterology, Tri-service General Hospital, Taipei, Taiwan.
authors.forename: Tsai-Yuan
authors.initials: TY
authors.lastname: Hsieh
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Fat-Moon
authors.initials: FM
authors.lastname: Suk
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital and University, Hualien, Taiwan.
authors.forename: Chi-Tan
authors.initials: CT
authors.lastname: Hu
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung, Taiwan.
authors.forename: Ming-Jong
authors.initials: MJ
authors.lastname: Bair
authors.affiliation: Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Cheng-Chao
authors.initials: CC
authors.lastname: Liang
authors.affiliation: Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yung-Chao
authors.initials: YC
authors.lastname: Lei
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Jin-Shan Branch, New Taipei City, Taiwan.
authors.forename: Tai-Chung
authors.initials: TC
authors.lastname: Tseng
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chi-Ling
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D004932:Esophageal and Gastric Varices / Q000453:epidemiology; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000401:mortality*; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012189:Retrospective Studies; D013624:Taiwan; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D000509:alpha-Fetoproteins; C413685:entecavir; D006147:Guanine
keywords: antiviral therapy; liver cancer; nucleos(t)ide analogue; spontaneous bacterial peritonitis; variceal bleeding