Young-onset hepatocellular carcinoma following double outlet right ventricle surgery without liver congestion: a case report with genetic analysis.

AIM: Congenital heart disease (CHD) can lead to liver dysfunction and HCC, typically through congestion, hypoxia, or low cardiac output. However, HCC development without these factors is not well understood.

METHODS

We report a 16-year-old girl with a history of double outlet right ventricle surgery in infancy, without Fontan procedure. Imaging and histology confirmed HCC without liver fibrosis, inflammation, or congestion. Whole exome sequencing was performed on tumor and non-tumor liver tissue. Genes associated with both CHD and HCC were identified from public databases, and protein expression was assessed by immunohistochemistry.

RESULTS

Among 589 genes associated with both CHD and HCC, 55 showed high-priority mutations in this case. The tumor carried mutations in known HCC-related genes, including MUC16 (CA125) and PABPC1. Immunostaining showed decreased expression of both proteins in tumor and non-tumor regions. Additional tumor-specific mutations in MAP3K1 and HNF1A were found, though protein expression was low.

CONCLUSION

This case suggests that non-cirrhotic, early-onset HCC may arise in congenital heart disease patients even without hepatic congestion, implying a different mechanism from post-Fontan hepatocarcinogenesis. Genetic factors may contribute, and screening should be considered in high-risk cases regardless of liver function.