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Original research
Haemodynamic and prognostic associations of liver fibrosis scores in Fontan-associated liver disease
  1. Irene Martin de Miguel1,
  2. Patrick S Kamath2,
  3. Alexander C Egbe1,
  4. C Charles Jain1,
  5. Frank Cetta3,
  6. Heidi M Connolly1,
  7. William R Miranda1
  1. 1 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
  2. 2 Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
  3. 3 Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr William R Miranda, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA; miranda.william{at}


Objectives Fontan-associated liver disease (FALD) is universal post-Fontan palliation; however, its impact on survival remains controversial and current diagnostic tools have limitations. We aimed to assess the prognostic role of liver fibrosis scores (aminotransferase to platelet ratio [APRI] and fibrosis-4 [FIB-4]) and their association with haemodynamics and other markers of liver disease.

Methods 159 adults (age ≥18 years) post-Fontan undergoing catheterisation at Mayo Clinic, Minnesota, between 1999 and 2017 were included. Invasive haemodynamics and FALD-related laboratory, imaging and pathology data were documented.

Results Mean age was 31.5±9.3 years, while median age at Fontan procedure was 7.5 years (4–14). Median APRI score (n=159) was 0.49 (0.33–0.61) and median FIB-4 score (n=94) was 1.12 (0.71–1.65). Correlations between APRI and FIB-4 scores and Fontan pressures (r=0.30, p=0.0002; r=0.34, p=0.0008, respectively) and pulmonary arterial wedge pressure (r=0.25, p=0.002; r=0.30, p=0.005, respectively) were weak. Median average hepatic stiffness by magnetic resonance elastography was 4.9 kPa (4.3–6.0; n=26) and 24 (77.4%) showed stage 3 or 4 liver fibrosis on biopsy; these variables were not associated with APRI/FIB-4 scores. On multivariable analyses, APRI and FIB-4 scores were independently associated with overall mortality (HR 1.31 [1.07–1.55] per unit increase, p=0.003; HR 2.15 [1.31–3.54] per unit increase, p=0.003, respectively).

Conclusions APRI and FIB-4 scores were associated with long-term all-cause mortality in Fontan patients independent of other prognostic markers. Correlations between haemodynamic status and liver scores were weak; furthermore, most markers of liver fibrosis failed to correlate with non-invasive indices, underscoring the complexity of FALD.

  • fontan procedure
  • biomarkers
  • cardiac catheterisation
  • congenital abnormalities

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • Contributors IMdM and WRM: study design, data abstraction/analysis and drafting of the manuscript. PSK, ACE, CCJ, FC, HMC: critical review of the manuscript. Guarantor: WRM.

  • Funding Dr Egbe is supported by National Heart, Lung, and Blood Institute (NHLBI) grants (R01 HL158517 and K23 HL141448).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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