title: Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma.
abstract: OBJECTIVE
  Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions.
  
  
  METHODS
  We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated.
  
  
  RESULTS
  Eleven studies from both high and low prevalence regions were identified. All studies except those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26-1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82), and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias.
  
  
  CONCLUSIONS
  Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers.
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Palmer
authors.forename: Tushar
authors.initials: T
authors.lastname: Patel
mesh_terms: D001650:Bile Duct Neoplasms / Q000453:epidemiology*; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000453:epidemiology*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology*; D012307:Risk Factors