Prevalence, Risk Factors, and Prognosis for Fontan-Associated Liver Disease: A Systematic Review and Exploratory...

Patients with Fontan circulation are at risk of progressive liver disease, but the prevalence and risk factors for Fontan-associated liver disease (FALD) remain unclear.

The aim of the study was to review unbiased data on FALD prevalence, diagnostic methods, risk factors, and prognostic significance, and to undertake exploratory meta-analysis on available data.

This systematic review included studies with unselected FALD screening. Outcomes were imaging or biopsy-proven cirrhosis, advanced fibrosis, portal hypertension, and hepatocellular carcinoma. Exploratory meta-analysis was performed, as well as subgroup analyses and meta-regression to explore contributors towards outcome heterogeneity.

Thirty-seven studies comprising 5,701 patients were included, with a median of 17 years of follow-up post-Fontan completion. All estimates of FALD were highly heterogeneous, reflecting variable patient factors and institutional practices. Cirrhosis was diagnosed in 21% of patients, but ranged from 0% to 76%. Advanced fibrosis without cirrhosis was noted in 30%, portal hypertension in 17%, and hepatocellular carcinoma in 2%, also with significant heterogeneity. Subgroup analysis and meta-regression highlighted several factors that contributed to such heterogeneity. It was found that cirrhosis was less commonly diagnosed by biopsy than by imaging (10% vs 26%). Other risk factors for cirrhosis included years post-Fontan completion, atriopulmonary Fontan, moderate or greater ventricular dysfunction, and higher pulmonary capillary wedge pressure. Qualitative synthesis noted FALD to be associated with elevated risk of cardiovascular and all-cause mortality.

Liver disease is common post-Fontan completion, though prevalence varies widely. Several risk factors should guide patient screening. A universal, prognostically meaningful FALD definition is needed to advance research and clinical care.