Comparisons of global incidence and risk factor profiles of hepatocellular carcinoma and intrahepatic cholangiocarcinoma

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), the most prevalent primary liver cancer subtypes, present significant global health challenges. We aimed to comprehensively compare their incidence rates, risk factors, and potential preventability. MATERIALS AND METHODS: We analyzed liver cancer histological subtypes from Cancer Incidence in Five Continents Volume XII and assessed 85 modifiable risk factors for HCC and iCCA using the UK Biobank data. We calculated population attributable fraction to assess the population preventability of the cancers. RESULTS: Incidence data from 49 countries revealed a moderate positive correlation between the incidences of HCC and iCCA (ρ=0.41, P=0.003), with the highest rates observed in the Republic of Korea (15.6 vs 3.3 per 100,000, respectively). The global variation of HCC incidence was more pronounced than iCCA. After applying a Bonferroni correction for p-value, we identified 42 modifiable risk factors for HCC (n=470) and eight for iCCA (n=508). The effects of nearly all risk factors were more pronounced for HCC than for iCCA. Up to 83.3 % of HCC cases could be attributed to modifiable risk factors, although the preventable fraction varied across subpopulations. By contrast, only 37.7 % of iCCA cases were attributable to such factors, and the preventable fraction remained consistent across subgroups. CONCLUSIONS: Our findings reveal the distinct yet partly overlapping epidemiological characteristics of HCC and iCCA, emphasizing the urgent need to clarify risk factors for iCCA. However, these findings may not be globally applicable, as modifiable risk factors can differ across regions due to varying exposures.