Non-invasive Investigations for the Diagnosis of Fontan-Associated Liver Disease in Pediatric and Adult Fontan Patients

Abstract

Fontan-associated liver disease (FALD) is a serious complication related to the chronically elevated venous pressure and low cardiac output of this abnormal circulation. However, diagnostic markers for this condition are limited. We hypothesized that specific tests for fibrosis developed for other chronic liver diseases would identify a higher prevalence of FALD than ultrasound and standard laboratory tests and that identified abnormalities would correlate with time post-Fontan. In this cross-sectional study, we assessed 19 children (average age 8.4 ± 4.3 and 5.4 ± 4.1 years post-Fontan) and 8 adults (average age 31.5 ± 8.9 and 21.1 ± 4 years post-Fontan) using standard serum laboratory investigations assessing hepatic integrity and function, the FibroTest, liver ultrasound, and transient elastography (FibroScan). In adult Fontan patients, hemoglobin, C-reactive protein, and gamma-glutamyl transpeptidase were significantly increased, and white blood cell and platelet counts were significantly decreased in comparison to the pediatric cohort. International normalized ratio was mildly elevated in both children and adults. FibroTest results were suggestive of fibrosis regardless of time post-Fontan. FibroScan measurements were significantly correlated with time post-Fontan, but the incidence of ultrasound-detected liver abnormalities was variable. No cases of hepatocellular carcinoma were identified. Abnormalities suggestive of FALD occur in both children and adults post-Fontan. Select laboratory tests, and possibly ultrasound and FibroScan in some patients, appear to have the most promise for the non-invasive detection of FALD.

Liver abnormalities and post‐transplant survival in pediatric Fontan patients

“…Recently, Friedrich‐Rust et al demonstrated that the peripheral biomarkers Fibrotest/Fibrosure and Actitest (Biopredictive, Paris, France) successfully detected the presence of liver fibrosis and correlated with disease progression in Fontan patients. Fidai et al reported similar results in a study that included pediatric and adult Fontan patients. However, a recent report by Wu et al showed that Fibrosure (LabCorp, Burlington, NC, USA) and hyaluronic acid did not correlate with the degree of hepatic fibrosis and did not predict cirrhosis in a population of adult Fontan patients.…”

“…Along with ultrasound, computed tomography and magnetic resonance imaging have been evaluated. More recently, measures of liver stiffness have been utilized to identify liver fibrosis in Fontan patients, including transient elastography, ARFI, and SWE . Although liver imaging and measures of liver stiffness have been shown to accurately identify abnormal liver architecture, these findings often do not correlate with clinical features and synthetic liver function in Fontan patients.…”

A composite noninvasive index correlates with liver fibrosis scores in post-Fontan patients: Preliminary findings

“…Also, we previously reported a significant correlation in Fontan patients between TFS and MELD‐XI scores . Additionally, past reports, by others and by us, had noted increasing fibrosis scores with time post‐Fontan . Nevertheless, time data had significant variability.…”

FibroSURE and elastography poorly predict the severity of liver fibrosis in Fontan‐associated liver disease

“…Fidai et al used both TE with FibroSURE to assess for signs of FALD in a group of children and adults. They noted a significant correlation between the degree of liver stiffness and time post‐Fontan.…”