Non-invasive biomarkers of liver disease as prognostic indicators in patients with Fontan circulation

BACKGROUND: The Fontan procedure is associated with long-term cardiac and non-cardiac complications and early mortality. Recent data suggest that some fibrosis scores may offer prognostic insight for individuals with Fontan circulation. This study aimed to investigate whether biomarkers of liver fibrosis can predict transplant-free survival in Fontan circulation. METHODS: This was a retrospective observational cohort study of 334 adults with Fontan circulation who had FibroSURE testing between 2008 and 2022 at a large-volume adult congenital heart disease centre. FibroSURE score, Aminotransferase-to-Platelet Ratio Index (APRI), fibrosis-4 (FIB-4) and Model for End-stage Liver Disease eXcluding INR (international normalised ratio) (MELD-XI) were recorded and analysed against clinical outcomes. RESULTS: There were 664 FibroSURE results during the study period with 83 (13%) above the nominal cut-off predicting cirrhosis (>0.74). There were 37 deaths (11%) and four transplants (1%) over a median follow-up of 5.6 years (IQR 2.7-9.9). After adjusting for age at FibroSURE and history of hepatitis C, each 0.1 increase in FibroSURE score remained associated with a 1.19-fold increased hazard of death or transplant (95% CI 1.02 to 1.40, p=0.032), and FibroSURE >0.74 remained associated with a 3.26-fold increased hazard of death or transplant (95% CI 1.62 to 6.59, p=0.001). In 314 patients where FibroSURE, APRI, FIB-4 and MELD-XI were all available, FibroSURE >0.74 (HR 5.11, 95% CI 2.66 to 9.83, p0.5 (HR 2.56, 95% CI 1.36 to 4.81, p=0.004), FIB-4 >1.45 (HR 5.07, 95% CI 2.67 to 9.64, p18 (HR 24.1, 95% CI 5.51 to 106, p