Abstract 4372594: Cholate clearance as assessed by HepQuant-SHUNT is predictive of clinical outcomes in individuals with Fontan circulation

Introduction: 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, and is abnormal in those with FC. We aim to explore the association between cholate clearance and clinical outcomes in this population. Hypothesis: Higher SHUNT% (systemic hepatic filtration rate [HFR]/portal HFR, an estimate of porto-systemic shunting) is associated with increased risk of death/transplant and is predictive of adverse clinical events. Methods: Two center prospective study of Fontan patients ≥ 18 years from University of Pennsylvania [Penn] and Northwestern University [NW]. Hepatic clearance of orally administered d4-cholate and intravenously administered 13C-cholate were measured in peripheral venous samples and calculated as portal HFR, systemic HFR, and SHUNT%. Primary outcome was transplant-free survival. Association between SHUNT% and transplant-free survival was assessed by Kaplan-Meier curves and the log-rank test for elevated SHUNT (>30%) and Cox regression for continuous SHUNT%. Secondary outcome was composite of death, transplant, new onset heart failure, ascites, protein losing enteropathy, or hepatocellular carcinoma. Logistic regression was used to evaluate the association between continuous SHUNT% and composite outcome. Sensitivity, specificity, and AUC were calculated. Results: Fifty participants (35 Penn, 15 NW) were enrolled. The Penn cohort was younger (median age 30 [IQR 25 – 37] vs 36 [IQR 30 – 41] years; p= 0.075) with shorter median follow-up (4.0 [IQR 3.4 – 4.8] vs 7.1 [IQR 5.0 – 8.9] years; p = 0.006). The composite outcome was reached in 14/50 (29%) including death (n=4), combined heart-liver transplant (n=4), or both (n=2). Unadjusted 1-year, 3-year, and 5-year transplant-free survival was 96%, 94%, and 79%, respectively. Figure 1 shows survival probability by SHUNT%. For every 10% incremental increase in SHUNT%, there was a 60% higher risk of death/transplant (95% CI 1.14 – 2.27; p = 0.006) and 70% higher odds of composite outcome (95% CI 1.05 – 3.03; p=0.045), adjusted for institution. SHUNT% >30% and institution identified those with composite outcome with sensitivity 64%, specificity 91%, and accuracy 83% (Figure 1). Conclusions: Higher SHUNT% is associated with lower transplant-free survival in individuals with FC and has modest discrimination in identifying those who experience future adverse clinical events.