Liver Fibrosis Scores Are Associated With Resting and Exercise Fontan and Pulmonary Artery Wedge Pressures: Insights Into FALD.

Abstract

Alterations in liver perfusion and venous hypertension have been implicated in the pathophysiology of Fontan-associated liver disease (FALD). However, the correlation between exercise hemodynamics and markers of FALD have not been studied. We performed a retrospective review of 32 consecutive adults undergoing exercise catheterisation at the Mayo Clinic, Minnesota. Invasive hemodynamics were correlated with aspartate transaminase to platelet ratio index (APRI) and the Fibrosis-4 (Fib-4) score, well validated surrogates of liver fibrosis. The mean age was 30.9 ± 7 years. The mean APRI was 0.5±0.2 and the mean Fib-4 score 1.3 ± 0.8. Fib-4 scores correlated with spleen size on abdominal imaging (r= 0.40; P= 0.03). Resting Fontan pressure was 13.9 ± 3.9 mm Hg and pulmonary artery wedge pressure (PAWP) 10.0 ± 3.5 mm Hg. At peak exercise (69.4 ± 23.2 W), Fontan pressures increased to 26.5 ± 6.2 mm Hg and PAWP to 22.4±7.1 mm Hg. APRI and Fib-4 score were directly related to Fontan pressure and PAWP at rest and during exercise, and inversely related to exercise arterial O2 saturation. Fib-4 inversely correlated with O2 delivery indices. Similarly, when categorising patients according to high APRI (>0.5 vs ≤ 0.5) or Fib-4 score (≥ 1.45 vs < 1.45) according to previously proposed cutoffs for diagnosis of liver fibrosis, those with elevated scores had higher resting and exercise Fontan and PAWP pressure with lower O2 arterial saturation. ARPI and Fib-4 score correlated with resting and exercise Fontan pressure and PAWP. In addition, Fib-4 scores were inversely related to O2 delivery indices. These findings support a role played by hepatic venous hypertension and reduced O2 supply in patients with FALD.