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

Background: 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.Methods: We performed a retrospective review of 32 consecutive adults undergoing exercise catheterisation at the Mayo Clinic, Minnesota. Invasive hemodynamics were correlated with aspartate trans-aminase to platelet ratio index (APRI) and the Fibrosis-4 (Fib-4) score, well validated surrogates of liver fibrosis.Results: 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(2) saturation. Fib-4 inversely correlated with O-2 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 O-2 arterial saturation.Conclusions: APRI and Fib-4 score correlated with resting and exercise Fontan pressure and PAWP. In addition, Fib-4 scores were inversely related to O-2 delivery indices. These findings support a role played by hepatic venous hypertension and reduced O-2 supply in patients with FALD.