title: Increased risk of hepatocellular carcinoma in chronic hepatitis C patients with new onset diabetes: a nation-wide cohort study.
abstract: BACKGROUND
  The impact of diabetes for hepatocellular carcinoma (HCC) development in chronic hepatitis C (CHC) patients remains controversial.
  
  
  OBJECTIVE
  To investigate the risk of HCC in CHC patients who develop new onset diabetes.
  
  
  METHODS
  We conducted a nation-wide cohort study by using Taiwanese National Health Insurance Research Database, which comprised of data from >99% of entire population. Among randomly sampled one million enrollees, 6251 adult CHC patients were identified from 1997 to 2009. Diabetes was defined as new onset in the patient who was given the diagnosis in the years 1999-2009 but not in 1997-1998. The cohorts of CHC with new onset diabetes (n = 1100) and 1:1 ratio age-, gender-, and inception point (onset date of diabetes) matched nondiabetes (n = 1087) were followed up from the inception point until the development of HCC, withdrawal from insurance, or December 2009.
  
  
  RESULTS
  After adjustment for competing mortality, patients with new onset diabetes had a significantly higher cumulative incidence of HCC (Relative Risk = 1.544, 95% CI = 1.000-2.387, modified log-rank test, P = 0.047) as compared to those without. After adjustment for age, gender, cirrhosis, hyperlipidaemia, CHC treatment, diabetes treatment, comorbidity index, obesity and statins therapy by Cox proportional hazard model, diabetes was still an independent predictor for HCC (hazard ratio (HR) = 1.906, 95% CI = 1.102-3.295, P = 0.021). The risk for HCC was increased in those who were 40-59 years old, independent of other variables (HR = 3.086, 95% CI = 1.045-9.112, P = 0.041), and after adjustment for competing mortality (modified log-rank test, P = 0.009).
  
  
  CONCLUSIONS
  Chronic hepatitis C patients who develop diabetes are at an increased risk of hepatocellular carcinoma over time.
authors.affiliation: Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.|School of Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan.|Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Huang
authors.affiliation: Department of Medical Research, Cathay General Hospital Medical Center, Taipei, Taiwan.
authors.forename: T-C
authors.initials: TC
authors.lastname: Wang
authors.affiliation: Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.|School of Medicine, Fu-Jen Catholic University College of Medicine, Taipei, Taiwan.
authors.forename: S-S
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Department of General Medicine, School of Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.
authors.forename: S-C
authors.initials: SC
authors.lastname: Fu
authors.affiliation: Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.|School of Medicine, Fu-Jen Catholic University College of Medicine, Taipei, Taiwan.
authors.forename: J-T
authors.initials: JT
authors.lastname: Hu
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: C-J
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan.
authors.forename: J-H
authors.initials: JH
authors.lastname: Kao
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.|Genomics Research Center, Academia Sinica, Nankang, Taiwan.
authors.forename: D-S
authors.initials: DS
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000453:epidemiology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications / Q000453:epidemiology; D008113:Liver Neoplasms / Q000150:complications / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology