Predictive value of biomarkers of hepatic fibrosis in adult Fontan patients

J Heart Lung Transplant. 2017 Feb;36(2):211-219. doi: 10.1016/j.healun.2016.07.011. Epub 2016 Jul 27.


Background: Hepatic fibrosis is highly prevalent in individuals with Fontan circulation. FibroSure (LabCorp, Burlington, NC) and hyaluronic acid (HA) have been validated for assessment of hepatic fibrosis in several forms of liver disease. We sought to determine whether these tests could identify Fontan patients with advanced hepatic fibrosis or cirrhosis.

Methods: Subjects who had liver biopsy and FibroSure or HA testing within 6 months of biopsy were identified from the Alliance for Adult Research in Congenital Cardiology Fontan Liver Health study. Biopsy specimens were scored for degree of sinusoidal and portal fibrosis on a 3- and 5-point scale, respectively. Histologic findings were correlated with FibroSure and HA results.

Results: The study included 27 subjects. Median age was 26.8 years (range, 17.4-59.8 years), and the median time since the Fontan surgery was 20.4 years (range, 12.0-31.3 years). FibroSure scores were elevated (>0.21) in 21 of 23 subjects (91%), and the scores for 3 (13%) suggested cirrhosis (>0.74). HA suggested cirrhosis (>46 ng/mL) in 3 of 17 subjects (18%). One subject died during the collection period. Eleven of 26 subjects (42%) had 4/5 or 5/5 portal fibrosis, consistent with cirrhosis; 17 (63%) had 3/3 sinusoidal fibrosis involving >66% of sinusoids. The FibroSure score and HA levels did not correlate with the degree of hepatic fibrosis and did not predict cirrhosis.

Conclusions: Abnormal biomarkers of hepatic fibrosis and specimen-proven hepatic fibrosis are common in adults with Fontan circulation. However, FibroSure and HA do not accurately predict the degree of histologic hepatic fibrosis. Further studies are needed to guide strategies for surveillance of liver disease in this population.

Keywords: FibroSure; Fontan; cirrhosis; congenital heart disease; congestive hepatopathy; hyaluronic acid.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Biopsy, Needle
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Fontan Procedure / adverse effects*
  • Fontan Procedure / methods
  • Heart Defects, Congenital / diagnosis
  • Heart Defects, Congenital / surgery
  • Humans
  • Hyaluronic Acid / blood*
  • Immunohistochemistry
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / pathology*
  • Liver Function Tests
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Assessment
  • Young Adult


  • Biomarkers
  • Hyaluronic Acid