Risk factors of intrahepatic cholangiocarcinoma in the United States: A case-control study

Background & Aims: The incidence of intrahepatic cholangiocarcinoma has been recently increasing in the United States. In this case-control study, we used the Surveillance, Epidemiology, and End Results-Medicare database to evaluate the prevalence of known risk factors for intrahepatic cholangiocarcinoma and explore other potential risk factors. Methods: We identified all patients with intrahepatic cholangiocarcinoma aged 65 years and older diagnosed between 1993 and 1999 in the population-based Surveillance, Epidemiology, and End Results registries (14% of the US population). Controls were randomly chosen from individuals without any cancer diagnosis in the underlying population of the Surveillance, Epidemiology, and End Results regions. We obtained information on risk factors from Medicare claims (parts A and 13) for all cases and controls with at least 2 years of continuous Medicare enrollment. Unadjusted and adjusted odds ratios were calculated in logistic regression analysis. Results: A total of 625 cases and 90,834 controls satisfied the inclusion and exclusion criteria. Cases were older than controls (78.7 vs. 76.5 years; P = .02) and were more likely to be male (48.3% vs. 36.8%; P < .0001). The racial composition was similar between cases and controls. Several risk factors were significantly more prevalent among cases. These included nonspecific cirrhosis (adjusted odds ratio, 27.2; P < .0001), alcoholic liver disease (adjusted odds ratio, 7.4; P < .0001), hepatitis C virus infection (adjusted odds ratio, 6.1; P < .0001), human immunodeficiency virus infection (adjusted odds ratio, 5.9; P = .003), diabetes (adjusted odds ratio, 2.0; P < .0001), and inflammatory bowel diseases (adjusted odds ratio, 2.3; P = .002). Conclusions: This population-based study shows that in addition to previously well described risk factors, several others could be associated with intrahepatic cholangiocarcinoma. These include hepatitis C virus, human immunodeficiency virus, liver cirrhosis, and diabetes.