Hepatic Fibrosis Is Universal Following Fontan Operation, and Severity is Associated With Time From Surgery: A Liver Biopsy and Hemodynamic Study

Abstract

BackgroundCongestive hepatopathy is a recognized complication of Fontan physiology. Data regarding the incidence of hepatopathy and risk factors are lacking.Methods and ResultsLiver biopsies and cardiac catherizations were performed as part of an evaluation offered to all patients ≥10 years after Fontan. Quantitative determination of hepatic fibrosis was performed using Sirius red staining with automated calculation of collagen deposition per slide (%CD). Biopsies from included subjects were compared to stained specimens from controls without known fibrotic liver disease. Patient characteristics, echocardiographic findings, and hemodynamic measures were evaluated as potential risk factors. The cohort consisted of 67 patients (31 female) at mean age of 17.3±4.5 years and mean time from Fontan of 14.9±4.5 years. Right ventricular morphology was present in 37 subjects. Median %CD by Sirius red staining was 21.6% (range 8.7% to 49.4%) compared to 2.6% (range 2.2% to 3.0%) in controls. There was a significant correlation between time from Fontan and degree of Sirius red staining (r=0.33, P<0.01). Serum liver enzymes and platelet count did not correlate with %CD. The median inferior vena cava pressure was 13 mm Hg (range 6‐24 mm Hg) and did not correlate with %CD. There was no difference in %CD based on ventricular morphology or severity of atrioventricular valve insufficiency.ConclusionsIn this cohort of predominantly asymptomatic children and adolescents electively evaluated after a Fontan operation, all exhibited evidence for hepatic fibrosis as measured by collagen deposition in the liver. Time from Fontan was the only factor significantly associated with collagen deposition. These findings demonstrate that liver fibrosis is an inherent feature of Fontan physiology and that the degree of fibrosis increases over time.

Late outcomes after the Fontan procedure in patients with single ventricle: a meta-analysis

“…It is known that Fontan configuration results in central venous congestion and reduced cardiac output. Some of the complications, such as PLE and hepatic dysfunction have been associated with the abnormal physiology offered by the Fontan circuit 27. Therefore, some argue that delaying the Fontan operation may help with postponing the onset of these complications.…”

Liver Cirrhosis and/or Hepatocellular Carcinoma Occurring Late After the Fontan Procedure ― A Nationwide Survey in Japan ―

“…A recent study confirmed that time after the Fontan procedure was the only factor significantly associated with collagen deposition, which suggested that liver fibrosis was an inherent feature of Fontan physiology. 20 However, no inflammation or hepatocellular damage was evident in patients undergoing the Fontan procedure, suggesting that fibrosis may be mediated by a non-inflammatory mechanism. 21 We could not determine the most reliable marker for the detection of liver disease in patients undergoing the Fontan procedure in the present study.…”

Short‐term outcomes of en bloc combined heart and liver transplantation in the failing Fontan

“…Post-operatively six patients were extubated at a median of 3 days (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), and the other three required tracheostomy at a median of 17 days (14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Post-operatively six patients were extubated at a median of 3 days (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), and the other three required tracheostomy at a median of 17 days (14)(15)…”

“…1 Fontan failure occurs due to systolic or diastolic dysfunction, atrioventricular valve regurgitation, arrhythmia, and/or lymphatic abnormalities. 4 Orthotopic heart transplantation (OHT) is a valuable treatment for Fontan failure. The pathophysiology of liver injury likely starts in utero and includes ischemia and tissue hypoxia associated with staged surgical palliation and the increased central venous pressure from total cavopulmonary anastomosis.…”