Analysis of risk factors of cholangiocarcinoma, role of diabetes mellitus and hepatitis B virus infection in the intrahepatic and extrahepatic cholangiocarcinoma: a retrospective case-based study in China.

BACKGROUND

The cause and carcinogenesis of cholangiocarcinoma (CCA) remain unclear. In this study, we conducted a population-based case-control study in China to evaluate the effects of diabetes mellitus (DM), hepatitis B virus (HBV) infection, and other potential risk factors for cholangiocarcinoma (CCA).

METHODS

A hospital-based, case-control study was conducted, including 245 CCA patients (168 with extrahepatic cholangiocarcinoma (eCCA) and 77 with intrahepatic cholangiocarcinoma (iCCA), diagnosed at The Second Affiliated Hospital of Harbin Medical University in China between January 2019 and June 2024, along with 490 healthy controls matched in a 2:1 ratio. Conditional logistic regression and the synergism index were used to analyze risk factors for cholangiocarcinoma and their potential correlations.

RESULTS

There was an association between DM, HBV infection, cholelithiasis, choledocholithiasis, hepatolithiasis, and thyroid diseases were significantly and positively correlated with CCA, with adjusted odds ratios (AOR = 1.53; 95% CI = 1.26-1.85; P < 0.001), (AOR = 2.55; 95% CI = 1.25-5.20; P < 0.010), (AOR = 1.71; 95% CI = 1.14-2.58; P < 0.009), (AOR = 4.67; 95% CI = 1.76-12.37; P < 0.002), (AOR = 3.00; 95% CI = 1.24-7.25; P < 0.015), and (AOR = 5.46; 95% CI = 2.04-14.60; P < 0.001) respectively. A synergistic interaction between HBV infection and DM was investigated using an interactive bar chart. In the subgroup analyses, the results for eCCA included DM (AOR = 1.40; 95% CI = 1.10-1.78; P < 0.006), cholelithiasis (AOR = 1.60; 95% CI = 1.14-2.31; P < 0.013), CBD stones (AOR = 4.05; 95% CI = 1.47-11.12; P < 0.007), hepatolithiasis (AOR = 5.80; 95% CI = 1.50-22.40; P < 0.010), and thyroid diseases (AOR = 11.18; 95% CI = 2.57-48.5; P < 0.001), all of which were significant for eCCA. Whereas DM (AOR = 2.61; 95%CI = 1.52-4.48; P < 0.001), cholelithiasis (AOR = 4.34; 95%CI = 1.53-12.34; P < 0.006), hepatolithiasis (AOR = 3.55; 95%CI = 1.05-12.00; P < 0.042), and HBV infection (AOR = 3.55; 95%CI = 1.55-8.15; P < 0.003) were significant risk factors for iCCA. Synergistic interaction between HBV infection and DM was also observed, resulting in a stronger association. Furthermore, a history of cholecystectomy (AOR = 0.39; 95%CI = (0.15-0.99); p < 0.048) demonstrates a protective function.

CONCLUSION

This Chinese study found that DM is an independent risk factor for CCA, particularly iCCA, and also increases the risk of eCCA. HBV infection is exclusively associated with iCCA, whereas choledocholithiasis, hepatolithiasis, and DM can cause both eCCA and iCCA. CBD stones enhance CCA risk, especially eCCA. By understanding this synergy, effective prevention methods for high-risk CCA may be established.