Metabolic Syndrome Increases Cholangiocarcinoma Risk- Hepatology Feb.26

This large population-based cohort study evaluated the relationship between metabolic syndrome (MetS) and the risk of cholangiocarcinoma (CCA), including both intrahepatic and extrahepatic subtypes.

The study included nearly 4.9 million adults aged ≥40 years who underwent national health screening between 2012 and 2017, with follow-up through 2021. Over 35.9 million person-years, 6,117 cases of CCA were identified.

Individuals with metabolic syndrome had a 20% higher risk of cholangiocarcinoma compared with those without MetS (adjusted HR 1.20). The increased risk was consistent across subgroups defined by age, sex, liver enzyme levels, and comorbidities. Importantly, the association applied to both intrahepatic and extrahepatic CCA.

A clear dose–response relationship was observed: the more metabolic components present (central obesity, hypertension, hyperglycemia, dyslipidemia), the higher the CCA risk. Individuals with five metabolic components had a 67% increased risk compared with those without metabolic abnormalities. These findings remained robust after accounting for the competing risk of all-cause mortality.

Clinical implication: Metabolic syndrome is not only a cardiovascular and hepatometabolic concern but also an independent risk factor for biliary tract malignancy. Aggressive management of metabolic risk factors may have potential implications for reducing cholangiocarcinoma incidence.