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

Background: 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. Methods: 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. Results: 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). Conclusions: 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.