title: Metformin confers risk reduction for developing hepatocellular carcinoma recurrence after liver resection.
abstract: Hepatocellular carcinoma recurrence following liver resection remains a great concern. The study aims to examine the chemopreventive effect of metformin in patients undergoing liver resection for hepatocellular carcinoma from a population-based study.
  
  
  
  All patients registered as having hepatocellular carcinoma between January 1995 and December 2011 in a nationwide database were retrospectively analysed. Outcomes related to liver resection and the presence of diabetes mellitus were assessed. Prognosis in terms of the use of metformin was further explored, in which only patients in the long-term follow-up starting at 2 years were included for analysis.
  
  
  
  Patients with diabetes mellitus had a significantly poorer outcome than patients without diabetes mellitus. Among diabetes mellitus patients, metformin users had significantly better survival curves in both recurrence-free survival (P<.0001) and overall survival (P<.0001) after liver resection. The hazard ratio of metformin use in hepatocellular carcinoma patients with diabetes mellitus was 0.65 (P<.05, 95% CI=0.60-0.72) for hepatocellular carcinoma recurrence and 0.79 (P<.05, 95% CI=0.72-0.88) for overall survival after liver resection. The risk reduction in hepatocellular carcinoma recurrence after liver resection was significantly associated with a dose/duration dependent of accumulated metformin usage.
  
  
  
  Diabetes mellitus has an adverse effect on patients with hepatocellular carcinoma regardless of treatment modality. The use of metformin significantly reduces the risk of hepatocellular carcinoma recurrence and improves the overall outcome of patients after liver resection if patients survives the initial 2 years. Nonetheless, a prospective controlled study is recommended for validating the metformin use on preventing postoperative hepatocellular carcinoma recurrence.
authors: Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Kun-Ming
authors: KM
authors: Chan
authors: Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.|Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.
authors: Chang-Fu
authors: CF
authors: Kuo
authors: Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Jun-Te
authors: JT
authors: Hsu
authors: Office for Big Data Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors: Meng-Jiun
authors: MJ
authors: Chiou
authors: Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Yu-Chao
authors: YC
authors: Wang
authors: Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Tsung-Han
authors: TH
authors: Wu
authors: Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Chen-Fang
authors: CF
authors: Lee
authors: Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Ting-Jung
authors: TJ
authors: Wu
authors: Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Hong-Shiue
authors: HS
authors: Chou
authors: Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Wei-Chen
authors: WC
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000601:surgery*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009313:National Health Programs; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D013624:Taiwan / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: diabetic mellitus; hepatocellular carcinoma; liver resection; metformin