Prognostic Value of Liver and Spleen Stiffness in Patients with Fontan Associated Liver Disease (FALD): A Case Series with Histopathologic Comparison

Abstract

The Fontan operation is the current surgical procedure to treat single-ventricle congenital heart disease, by splitting the systemic and pulmonary circulations and thus permitting lifespan to adulthood for the majority of newborns. However, emerging data are showing that Fontan-associated liver disease (FALD) is an increasing related cause of morbidity and mortality in patients with the Fontan circuit. We described the clinical, laboratory, and transient elastography (TE) findings in a case series of adults with the Fontan circuit, and also correlated data with post-mortem histological features, aimed to define the prognostic value of TE in the staging of FALD. All patients presented signs of a long-standing Fontan failure, characterized by reoperation need, systemic ventricle dysfunction, and FALD stigmata (liver and spleen enlargement, portal vein and inferior vena cava dilation, and abnormal liver function tests). Liver and spleen stiffness (LS and SS) values were indicative of significant liver fibrosis/cirrhosis and the presence of suggestive portal hypertension (LS mean 35.9; range 27.3–44.7 kPa; SS mean 42.1, range 32.2–54.5 kPa). Post-mortem evaluations confirmed a gross hepatic architecture distortion in all cases. All patients died from severe complications related to liver dysfunction and bleeding. TE correlated well with pathological findings and FALD severity. We propose this validated and harmless technique to monitor liver fibrosis extension and portal hypertension over time in Fontan patients, and to identify the optimal timing for surgical reoperations or orthotopic-heart transplantation (OHT), avoiding a higher risk of morbidity and mortality in cases with severe FALD.

Cardiac and Liver Fibrosis Assessed by Multiparametric MRI in Patients with Fontan Circulation

“…The sample was relatively small, due to the rarity of the disease, and we did not perform liver biopsy in our patients. However, MRE has been validated as an effective method to assess liver stiffness and prior research has indicated an association between hepatic stiffness and histological fibrosis in different diseases, including patients with Fontan [40,52,53]. Although we did not have age-matched controls; we could demonstrate increased myocardial and liver fibrosis in patients despite their younger age compared to controls.…”

A Novel Strategy for the Mechanical Subpulmonary Support in Failing Fontan Patients

“… 19 Liver stiffness as determined by transient elastography correlates with the presence of fibrosis and allows for patient staging without the need for invasive biopsies 19 and for monitoring of FALD progression. 28 Murtuza et al 29 showed that patients with preserved ventricular function and moderate-to-severe liver fibrosis or VAST ≥ 2 were at higher risk of death.…”

Role of Transient Elastography to Stage Fontan-Associated Liver Disease (FALD) in Adults with Single Ventricle Congenital Heart Disease Correction

“…Thus, the FALD is assuming a novel clinical entity, characterized by a condition influencing both the general state (i.e., fatigue, cyanosis, short-breath, intolerance to effort, poor growth, sarcopenia) and systemic organs function (i.e., heart, lungs, kidney, gut) and both the subject risk of complications related to liver disfunction (i.e., ascites, spontaneous peritonitis, hepatic-renal syndrome, hepatocellular carcinoma, GE varices bleeding and encephalopathy) or to failing Fontan (i.e., pulmonary hypertension, PLE, arrythmias, plastic bronchitis, reduced heart output, dots blood) that significantly compromises the patient's life expectancy [16,22].…”

“…Nevertheless, this tool is not a standardized method, considering the congestive liver status in Fontan patients with possible overestimation of LS measurement [10,14]. Certain predictive scores based on serum markers were also developed for staging liver disease in different patient categories (i.e., with significant fibrosis or cirrhosis and with portal hypertension), but these models have been never applied or tested for FALD staging [15,16].…”