Predictive value of biomarkers of hepatic fibrosis in adult Fontan patients

https://doi.org/10.1016/j.healun.2016.07.011Get rights and content

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.

Section snippets

Study design

A total of 241 subjects consented to participate in the Alliance for Adult Research in Congenital Cardiology Fontan liver health study from all eligible individuals who presented to 1 of 6 United States adult congenital heart disease centers for evaluation from September 2009 through April 2012. Subjects were eligible for enrollment if they were aged ≥16 years and had previously undergone Fontan surgery. Exclusion criteria included a history of cardiac transplantation, known inherited forms of

Baseline characteristics

We identified 27 patients who had a liver biopsy and FibroSure or HA testing (25 with FibroSure and 17 with HA). The liver biopsy in 23 of 27 patients was performed through a transjugular approach, and 3 were performed percutaneously. One patient died during the data collection period and underwent liver evaluation at autopsy. The median age was 26.8 years (range, 17.4–59.8 years), and the median time since initial Fontan surgery was 20.4 years (range, 12.0–31.3). The most common congenital

Discussion

This study investigated the correlation between direct and indirect biomarkers of liver fibrosis and histologic fibrosis in patients with Fontan physiology. In our cohort of patients with a high prevalence of advanced-stage hepatic fibrosis, FibroSure and HA are inaccurate predictors for such.

The histologic features of liver disease typically seen in patients with Fontan circulation are dilated sinusoids; congestion, atrophy, and necrosis of the centrilobular hepatocytes; sinusoidal fibrosis;

Disclosure statement

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript. C.U. currently employed by Novartis.

The authors acknowledge the clinical and administrative staff of the Boston Adult Congenital Heart (BACH) and Pulmonary Hypertension Program for their support in the preparation of this manuscript.

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