Combined hepatocellular carcinoma (HCC) tumors have a distinct clinical course with worse overall survival compared to regular HCC, according to a population-based cohort study published in the Journal of Gastrointestinal and Liver Diseases

The histopathological identification of these cancers is therefore essential to further characterize them and to provide the right treatment to patients, a study found.

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There is currently no standardized treatment for combined HCC. The present study analyzed the clinical course, treatment, and outcome of 9144 patients with primary liver cancer in the Clinical Cancer Registry of Baden-Württemberg in Germany.

Of these, 6622 had HCC, 2356 had intrahepatic cholangiocarcinoma (iCCA), and 166 had combined HCC. In all 3 groups patients were predominantly male. Around half (48%) of patients with combined HCC were diagnosed as stage 4 cancers while only around a third (31%) of those with HCC were diagnosed as stage 4 cancer. On the contrary, the majority (64%) of those with iCCA were diagnosed as stage 4 cancer. 

The overall median survival of patients with combined HCC was worse at 9 to 13 months compared to those with regular HCC which was 15.5 months but comparable to those with iCCA, which was 11.8 months.

“Our large retrospective population-based study demonstrated that [combined HCC tumors appear to have a distinct clinical course with worse overall survival compared to HCC,” the researchers concluded. Our data support more frequent histological diagnosis to exclude or confirm [combined HCC] as a basis for a more adequate therapy assignment”. 

Combined HCC is a type of tumor that displays features of hepatocytic and cholangiocytic differentiation. This type of tumor is much rarer with an estimated incidence of 1 to 5% of primary liver cancers. CCA is the second most common primary malignancy of the liver, following HCC and is responsible for about 15% of all primary liver tumors.


Teufel A, Rodriguez I, Winzler C, et al. Clinical characterization of HCC/CCA mixed cancers in a population-based cohort. J Gastrointestin Liver Dis. Published online June 30, 2023. doi:10.15403/jgld-4893