History and exam

Key diagnostic factors

common

Key risk factors include age >50 years, cholangitis, choledocholithiasis, cholecystolithiasis, other structural disorders of the biliary tract, ulcerative colitis, primary sclerosing cholangitis, liver fluke infection, non-specific cirrhosis, alcoholic liver disease, hepatitis C virus, HIV infection, hepatitis B virus, chronic typhoid carrier, and exposure to thorium dioxide.

Occurs in around 90% of patients.[6]

uncommon

Occurs in around 35% of patients.[39]

Approximately 35% of patients may experience abdominal pain.[39]

Other diagnostic factors

uncommon

Occurs in approximately 26% of patients.[39]

Features of acute cholangitis. Occurs in 10% of patients.[39]

Rare.

Rare.

If obstructive jaundice is present.

If obstructive jaundice is present.

Intrahepatic cholangiocarcinoma may be an incidental finding and may be detected during surveillance imaging in patients with cirrhosis. One study reported that 28% of intrahepatic cholangiocarcinomas, and 4% of extrahepatic cholangiocarcinomas, presented incidentally.[40]​ Symptoms are typically associated with more advanced disease.[7]

Risk factors

strong

Approximately two-thirds of cholangiocarcinomas occur in patients aged between 50 and 70 years.[4]

Cholangitis increases the likelihood of intrahepatic cholangiocarcinoma, with an adjusted odds ratio (OR) of 8.8 and 95% confidence interval (CI) of 4.9 to 16.0.[12][13]

Although, historically, cholangitis has been related to an increased risk of extrahepatic cholangiocarcinoma, data are lacking on the strength of this association.

Choledocholithiasis increases the risk of intrahepatic cholangiocarcinoma, with an adjusted OR of 4.0, 95% CI of 1.9 to 8.5.[13]

Limited data are available with regard to the association with extrahepatic cholangiocarcinoma, but a historical association exists.

Cholecystolithiasis increases the risk of intrahepatic cholangiocarcinoma, with an OR of 4.0, 95% CI of 2.0 to 7.99.[12]

Limited data are available with regard to the association with extrahepatic cholangiocarcinoma, but a historical association exists.

Examples include bile duct adenoma, biliary papillomatosis, choledochal cyst, and Caroli's disease (non-obstructive dilation of the biliary tract).[8][21]​​

UC increases the risk of intrahepatic cholangiocarcinoma, with an OR of 2.3, 95% CI of 1.4 to 3.8.[13]

Data are lacking with regard to the association with extrahepatic cholangiocarcinoma, but a historical association exists.

PSC has been associated with high risk of cholangiocarcinoma, with its prevalence in patients with PSC ranging from 7% to 13%.[14] The risk of cholangiocarcinoma in patients with PSC increases with older age.[7]​ PSC also has a strong association with UC, another risk factor of cholangiocarcinoma; between 60% and 80% of all patients with PSC have a co-existing UC. The incidence of cholangiocarcinoma may be higher in patients with both conditions.[22]​ The American Association for the Study of Liver Diseases recommends that cholangiocarcinoma surveillance should be performed annually in adult patients with PSC (although not in those with small-duct PSC).[7]

Non-specific cirrhosis has a stronger association with intrahepatic cholangiocarcinoma, with an OR of 27.2, 95% CI of 19.9 to 37.1.[13]

Alcoholic liver disease increases the risk of intrahepatic cholangiocarcinoma, with an OR of 7.4, 95% CI of 4.3 to 12.8.[13]

Heavy drinking (>80 g of ethanol per day) has a strong association with intrahepatic cholangiocarcinoma (OR of 6.0, 95% CI of 2.3 to 16.7) and extrahepatic cholangiocarcinoma (OR of 4.0, 95% CI of 1.7 to 10.2).[23]

Clonorchis sinensis increases the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, with a relative risk (RR) of 2.7, 95% CI of 1.1 to 6.3.[9]

Clonorchis sinensis and Opisthorchis viverrini infestation have been related in East Asian countries with higher incidence of cholangiocarcinoma; the activation of the host immune system and the chronic inflammatory state are proposed as the initial factors in the epithelial transformation to cancer.

In South-East Asia, where incidence of cholangiocarcinoma is increased, chronic typhoid carriers have a sixfold risk of developing a hepatobiliary malignancy.[24]​​

HCV infection has a strong association with intrahepatic cholangiocarcinoma. In one study, the association showed an OR of 6.1, 95% CI of 4.3 to 8.6, while no association was found with extrahepatic cholangiocarcinoma, with an OR of 4.5, 95% CI of 0.8 to 45.7.[13]

HIV infection has been related to intrahepatic cholangiocarcinoma, with an OR of 5.9, 95% CI of 1.8 to 18.8.[13] HIV infection is known to increase the prevalence of cholangitis either directly or via other opportunistic infections (e.g., cytomegalovirus).[25]

HIV-related cholangitis could lead to changes similar to those induced by other inflammatory conditions of the bile duct that eventually result in cancer; it could be a confounding factor because HIV tends to co-occur with HCV infection.

HBV-infected patients have been found to have a higher prevalence of intrahepatic cholangiocarcinoma in several studies.[9][26][27]

Other studies have not found any association between intrahepatic cholangiocarcinoma and HBV infections; however, the number of patients studied was small.[13]

Exposure to thorium dioxide, such as thorotrast, a radioactive contrast agent used until the 1950s, results in an increased incidence of cholangiocarcinoma.[18]

weak

No clear association has been found.[12][13]

No clear association has been found.[12][13] Smoking may increase the risk of cholangiocarcinoma in patients with PSC.[28]

Occupational exposure to polychlorinated biphenyls (PCBs), isoniazid, oral contraceptives, and chronic typhoid carriers poses an increased risk of cholangiocarcinoma.[15][16][17][29]​​

There is a slight male predominance.[4]

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