Hepatic cholate clearance as assessed by HepQuant-SHUNT is associated with clinical outcomes in individuals with Fontan circulation

Fontan-associated liver disease [FALD] is universal in individuals with Fontan circulation [FC]. The dual cholate clearance test is a noninvasive, flow-dependent measure of liver function. We aim to explore the association between cholate clearance and clinical outcomes in this population. Prospective study of adults with FC ≥ 18 years from University of Pennsylvania [Penn] and Northwestern University [NU]. Hepatic clearance of oral d4-cholate and intravenous 13C-cholate were measured from peripheral venous blood and calculated as portal hepatic filtration rate [HFR], systemic HFR, and SHUNT% with elevated SHUNT% being >30%. Primary outcome was transplant-free survival. Association between SHUNT% and primary outcome was assessed using Kaplan-Meier curves and log-rank test or Cox regression. Secondary outcome was composite of death, transplant, new onset heart failure, ascites, protein losing enteropathy, or hepatocellular carcinoma. Association between SHUNT% and composite outcome was analyzed by logistic regression. Fifty participants (35 Penn, 15 NU) were enrolled. Unadjusted 1-, 3-, and 5-year transplant-free survival was 96%, 94%, and 79%, respectively. Individuals with elevated SHUNT% had significantly lower transplant-free survival at 5-years. The composite outcome was reached in 14/50 (29%), including death (n=4), combined heart-liver transplant (n=4), or both (n=2). Elevated SHUNT% was associated with 3.9-fold increase odds of composite outcome (95% CI 1.02 – 15.3; p=0.048). An increase in shunting of portal blood into the systemic circulation as quantified by SHUNT% is associated with decreased transplant-free survival in individuals with FC and has excellent discrimination in identifying those at risk for mid-term adverse clinical events. • Clinical Perspectives • Cholate clearance by the liver is decreased in Fontan-associated liver disease (FALD), a complication of palliated single ventricle disease after the Fontan operation. • Increased shunting of portal blood into the systemic circulation as quantified by a measure of cholate clearance, SHUNT%, is associated with decreased transplant-free survival and adverse clinical events in this population including new onset heart failure, protein-losing enteropathy, or hepatocellular carcinoma. • If validated, SHUNT% would be the first measure of liver function in FALD prognostic of survival and could help clinicians risk stratify individuals with Fontan circulation at risk for untoward outcomes.