Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a case-control study in China

The risk factors for cholangiocarcinoma are incompletely defined in China, especially for intrahepatic cholangiocarcinoma (ICC). We evaluated the risk factors for both ICC and extrahepatic cholangiocarcinoma (ECC).

A case-control study in which cases were cholangiocarcinoma patients referred to Peking Union Medical College Hospital (PUMCH) between 1998 and 2008 and controls were healthy individuals. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of PUMCH. Data on liver disease, family history, diabetes, smoking and drinking were collected by a retrospective review of the patients' records and health examination reports or by interview.

A total of 190 patients (61 ICC; 129 ECC) and 380 age- and sex-matched controls were enrolled. HBsAg (P<0.001) and anti-HBc without HBsAg (P=0.001) were significantly related to ICC. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were 18.1 (95% CI: 7.5-44.0) and 3.6 (95% CI: 1.7-7.6) respectively. Diabetes mellitus (P=0.007), cholecystolithiasis (P=0.004) and previous cholecystectomy (P<0.001) were significantly associated with ECC. The prevalence of cirrhosis was higher in ICC than that in ECC (P<0.001). Furthermore, on excluding the ICC patients with cirrhosis, ICC patients showed significant independent associations with HBsAg (OR: 7.3; 95% CI: 3.1-17.2) and anti-HBc without HBsAg (OR: 2.4; 95% CI: 1.1-5.2).

Cirrhosis and chronic hepatitis B virus infection are risk factors for ICC, while cholecystolithiasis, diabetes and previous cholecystectomy are risk factors for ECC.