부산대학교 도서관

Simple Summary: Fontan-associated liver disease (FALD) is a late sequela of single ventricle palliation. The long-term consequences of Fontan's physiology have a spectrum of outcomes resulting in chronic hepatic venous congestion, liver cirrhosis, hyperplastic nodules, and liver neoplasms that are both benign, such as hepatic adenoma (HA), and malignant, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). To date, genetic and molecular studies of HCC/CC contextual to FALD are lacking. We report the molecular profile of the heterogeneous group of tumors observed in the FALDs (HA, HCC, and CC) we studied with the aim of comparing any differences with the same tumors without FALD and identifying possible recurrent variables, such as molecular alterations, that could be predictive of clinical outcome. Purpose: Univentricular heart is corrected with the Fontan procedure (FP). In the long term, so-called Fontan-associated liver diseases (FALDs) can develop. The aim of this study is to analyze the molecular profile of FALDs. Methods: FALDs between January 1990 and December 2022 were reviewed for histology and immunohistochemistry, laboratory data, and images. Targeted next generation sequencing (NGS), performed on the DNA and RNA of both neoplastic and non-lesional liver tissue, was applied. Results: A total of 31/208 nodules > 1 cm in diameter were identified on imaging, but a liver biopsy was available for five patient demonstrating the following: one hepatocellular adenoma (HA), two hepatocellular carcinomas (HCCs), one fibrolamellar carcinoma (FLC), and one intrahepatic cholangiocarcinoma (ICC). Molecular analysis showed a copy number alteration involving FGFR3 in three cases (two HCCs and one ICC) as well as one HCC with a hotspot mutation on the CTNNB1 and NRAS genes. Tumor mutational burden ranged from low to intermediate. A variant of uncertain significance in GNAS was present in two HCCs and in one ICC. The same molecular profile was observed in a non-lesional liver. A DNAJB1-PRKACA fusion was detected only in one FLC. Conclusions: Neoplastic FALDs show some unusual molecular profiles compared with non-Fontan ones. The presence of the same alterations in non-lesional cardiac cirrhosis could contribute to the development of FALD. [ABSTRACT FROM AUTHOR]