September 18, 2019
2 min read

Several significant cholangiocarcinoma risk factors identified

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Results from a systematic review and meta-analysis revealed 13 risk factors for intrahepatic and extrahepatic cholangiocarcinoma, the most significant of which included biliary cysts and stones, cirrhosis, hepatitis B and hepatitis C.

Additionally, although diabetes was not among the strongest risk factors, increasing global rates of diabetes may be contributing to rising rates of cholangiocarcinoma (CCA).

“CCA typically presents late with non-specific symptoms,” Oliver Clements, MD, from Imperial College London in the United Kingdom, and colleagues wrote. “This is compounded by the lack of knowledge of risk factors in most cases and inaccurate screening tools to make the diagnosis of early, resectable disease uncommon. Beyond this stage, CCA is one of the most fatal cancers with a 5-year survival of approximately 5%.”

Their analysis comprised 25 studies published between 2007 and 2017 that contained data on patients who developed either intrahepatic CCA (iCCA) or extrahepatic CCA (eCCA). Results showed that choledochal cysts inferred the greatest risk for both iCCA (OR = 26.71; 95% CI, 15.8-45.16) and eCCA (OR = 34.94, 95% CI, 24.36-50.12).

The other risk factors for iCCA included cirrhosis (OR = 15.32; 95% CI, 9.33-25.15), cholelithiasis (OR = 3.38; 95% CI, 1.93-5.92), HBV (OR = 4.57; 95% CI, 3.43-6.09), HCV (OR = 4.28; 95% CI, 2.98-6.16), alcohol use (OR = 3.15; 95% CI, 2.24-4.41), cholecystocholithiasis (OR = 1.75; 95% CI, 1.97-3.16), inflammatory bowel disease (OR = 2.68; 95% CI, 1.79-4.01), type 2 diabetes (OR = 1.73; 95% CI, 1.47-2.04), smoking (OR = 1.25; 95% CI, 1.05-1.49), hypertension (OR = 1.1; 95% CI, 0.89-1.37), and obesity (OR = 1.14; 95% CI, 0.93-1.39).

The researchers observed the same risk factors for eCCA with some differing significance, including cirrhosis (OR = 3.82; 95% CI, 2.58-5.65), cholelithiasis (OR = 5.92; 95% CI, 3.09-11.32), HBV (OR = 2.11; 95% CI, 1.64-2.73), HCV (OR = 1.51; 95% CI, 0.96-2.36), alcohol use (OR = 1.75; 95% CI, 1.2-2.55), cholecystocholithiasis (OR = 2.95; 95% CI, 2.11-4.12), IBD (OR = 2.37; 95% CI, 1.34-4.22), type 2 diabetes (OR = 1.5; 95% CI, 1.31-1.71), smoking (OR = 1.69; 95% CI, 1.28-2.22), hypertension (OR = 1.21; 95% CI, 0.77-1.9), and obesity (OR = 1.2; 95% CI, 0.84-1.7).

Comparison between studies from Western countries such as the U.S., Denmark, and Italy, and Eastern countries including China, Taiwan, Japan, and South Korea, revealed a marginal difference for cirrhosis (c = –0.077; 95% CI, –0.168 to –0.015) and HBV (c = –0.151; 95% CI, –0.278 to –0.025) as risk factors for iCCA, but no difference for HCV and alcohol use.


“These geographical differences are interesting to observe and may be explained by the difference of risk exposure from both genetic variations and environmental factors,” Clements and colleagues wrote. They also noted the key finding in the degree of difference to which each risk factors correlated with either iCCA or eCCA.

“The findings are concordant with the primary locations that are targeted by the specific factors. Viral hepatitis and cirrhosis primarily affect the intrahepatic bile ducts, whereas cholelithiasis, choledocholithiasis and cholecystolithiasis affect the extrahepatic bile ducts,” they wrote. “The risk factors associated with both iCCA and eCCA are [type 2 diabetes], alcohol and smoking, which are likely to be general risk factors for malignancy; while [choledochal cysts] develops in both the intrahepatic and extrahepatic bile ducts.” – by Talitha Bennett

Disclosures: The authors report no relevant financial disclosures.