Alterations in Liver Perfusion in Adults With Fontan Circulation as Assessed by Dual Cholate Clearance

Fontan circulation (FC) in complex congenital heart disease is characterized by altered hemodynamics and associated with Fontan-associated liver disease. Patients with FC may exhibit abnormalities in cholate clearance due to abnormal perfusion. We aimed to compare cholate clearance in adults with FC to healthy controls and explore associations between cholate clearance and clinical features.

This is a prospective cohort study of patients with FC ≥18 years of age between 2019 and 2022. Systemic and portal hepatic clearance of cholate was assessed using a dual cholate clearance assay (HepQuant Shunt), measuring systemic and portal hepatic filtration rates (HFRs). Systemic HFR/portal HFR ratio (SHUNT%) was calculated. Participants with FC and healthy controls were compared using the Fisher exact test and Wilcoxon test. Univariable regression and multivariable analyses determined associations with clinical variables. There were 35 participants with FC (54% women; median age 29.0 years [interquartile range, 24.0-36.0], 91% White) and 26 controls. In addition to lower platelet counts and higher aspartate aminotransferase to platelet ratio index, and Fibrosis-4 indices, FC participants had lower systemic HFR and portal HFR. SHUNT% was comparable with controls but ranged from 8% to 76%, with 8 (23%) having SHUNT% >30%. In those with FC, increase in SHUNT% was associated with elevated Fontan pressure, higher aortopulmonary collateral flow, decreased oxygen saturation, elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, thrombocytopenia, and Fibrosis-4 ≥1.45.

Cholate clearance, as defined by systemic and portal HFR, is impaired in those with FC. Features of worse Fontan physiology correlate with higher SHUNT%, supporting the hypothesis that hemodynamic derangements play a role in progression of Fontan-associated liver disease.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03726229.