title: Diabetes, hepatocellular carcinoma, and mortality in hepatitis C-infected patients: A population-based cohort study.
abstract: OBJECTIVE
  The effect of diabetes mellitus (DM) on the development of hepatocellular carcinoma (HCC) and all-cause mortality after HCC development in chronic hepatitis C virus (HCV)-infected patients remains inconclusive. This cohort study aimed to investigate these issues using the Taiwanese National Health Insurance Research Database.
  
  
  METHODS
  We retrieved and enrolled newly diagnosed DM patients with HCV from the Longitudinal Cohort of Diabetes Patients database. Propensity score matching-including age, sex, alcohol-related liver disease, and baseline liver cirrhosis-was used to identify and enroll HCV patients without DM from the Longitudinal Health Insurance Database (n = 1686). A multi-state model was used to investigate transitions from "start-to-HCC," "start-to-death," and "HCC-to-death."
  
  
  RESULTS
  The multi-state model showed higher cumulative hazards for "start-to-HCC," "start-to-death," and "HCC-to-death" transitions in the DM (vs non-DM) cohort. The cumulative probability of death with or without HCC after 10 years of follow-up was higher in the DM cohort than in the non-DM cohort. Multivariable transition-specific Cox models demonstrated that DM significantly increased the risk for transition from "start-to-HCC" (adjusted hazard ratio [aHR] 1.36; 95% confidence interval [CI] 1.16-1.59; P < 0.001), "start-to-death" (aHR 2.61; 95% CI: 2.05-3.33; P < 0.001), and "HCC-to-death" (aHR 1.36; 95% CI 1.10-1.68; P = 0.005). The effect of liver cirrhosis on "start-to-HCC" and "start-to-death" transitions decreased over time, particularly within 2 years.
  
  
  CONCLUSIONS
  Diabetes mellitus increased the risk of HCC development in HCV-infected patients and the risk of all-cause mortality in patients with or without HCC.
authors.affiliation: Department of General Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan.|Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Ting-Shuo
authors.initials: TS
authors.lastname: Huang
authors.affiliation: Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.|Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chih-Lang
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Mu-Jie
authors.initials: MJ
authors.lastname: Lu
authors.affiliation: College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan.|Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Kung-Hao
authors.initials: KH
authors.lastname: Liang
authors.affiliation: Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Chi-Chin
authors.initials: CC
authors.lastname: Sun
authors.affiliation: Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.|Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Yu-Chiau
authors.initials: YC
authors.lastname: Shyu
authors.affiliation: Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.|Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Chien
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000401:mortality*; D015331:Cohort Studies; D048909:Diabetes Complications / Q000150:complications*; D003920:Diabetes Mellitus; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000401:mortality*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D012306:Risk; D013997:Time Factors
keywords: death; diabetes mellitus; hepatitis C virus; liver cancer