Non-invasive assessment of severe liver fibrosis in patients with Fontan-associated liver disease: The VALDIG-EASL FONLIVER cohort

Background & aims: Fontan-type surgery is a palliative procedure for congenital heart disease with univentricular physiology that may, in the long term, lead to advanced chronic liver disease. Herein, we assessed the accuracy of conventional non-invasive models for assessing liver fibrosis in the context of Fontan circulation and developed a new risk score employing non-invasive tools.

Methods: A prospective, cross-sectional, observational study was conducted across five European centers and encompassing all consecutive adult patients with Fontan circulation, liver biopsy and non-invasive tests (e.g. elastography, APRI, and FIB-4). The primary outcome was the identification of severe liver fibrosis on biopsy. Multivariable logistic regression identified non-invasive predictors of severe fibrosis, leading to the development and internal validation of a new scoring model named the FonLiver risk score.

Results: In total, 217 patients (mean [SD] age, 27.9 [8.9] years; 50.7% males) were included. Severe liver fibrosis was present in 47.9% (95% CI 41.2%-54.5%) and correlated with a lower functional class, protein-losing enteropathy, and compromised cardiopulmonary and systemic hemodynamics. The final FonLiver risk score incorporated liver stiffness measurement using transient elastography and platelet count and demonstrated strong discrimination and calibration (AUROC of 0.81). The FonLiver risk score outperformed conventional prediction models (e.g. APRI and FIB-4), which all exhibited worse performance in our cohort (AUROC <0.70 for all).

Conclusion: Severe liver fibrosis is prevalent in adults following Fontan-type surgery and can be effectively estimated using the novel FonLiver risk score. This scoring system can be easily incorporated into the routine assessment of patients with Fontan circulation.

Impact and implications: Fontan-type surgery is used as a palliative procedure for congenital heart disease with univentricular physiology that may, in the long term, lead to advanced chronic liver disease. The severity of liver fibrosis progression has been proposed as a surrogate for failing Fontan hemodynamics as well as worse outcomes after heart transplantation. The development of FALD screening protocols would facilitate the early detection of advanced fibrosis and anticipate interventions to optimize the Fontan circulation, thereby improving outcomes. In our international series, we have developed the FonLiver risk score to predict severe fibrosis, that can be easily incorporated into the routine assessment of patients with Fontan circulation.