Evaluation of Fontan-associated liver disease by a novel predictive index. Data from the prospective Fontan cohort monitored in a liver centre

Background The Fontan procedure restores survival from infancy to adulthood in those born with univentricular hearts (UH). Unfortunately, these patients can develop complications, including FALD with the onset of liver cirrhosis and portal hypertension (PH), which can lead to major events and Fontan-failure (Ff) also affecting life expectancy of patients. Purpose We aimed: 1) to identify cases with advanced FALD (a-FALD) or cardiogenic cirrhosis (CC) and PH by dynamic monitoring of liver (LS) and spleen (SS) stiffness and other standard scores for non-invasive liver fibrosis estimation; 2) to validate a simple P-CC index for the prediction and prognosis ofmajor events onset. Methods 148 patients : 88 males (59.4%), mean age 28.5 + 9.0 years, with UH (25 HLHS; 67 TA; 29 DILV; 27 DORV) and Fontan circuit (28 atrium-pulmonary, 41 lateral tunnel; 79 extracardiac), showing a mean time since Fontan of 22.5 ± 10.3 years. Patients underwent repeated evaluation of specific blood test (BT) panel and LS and SS by transient elastography (TE), ultrasound (US) and TC or RMN imaging, during study follow-up (FU) of 46,3 ± 19,6 months. Unfortunately, 7 patients were asplenic and therefore unfit to receive all the necessary measurements. Results Seven selective criteria (lymphocytes, PLTS and GGT, size of spleen, diameters of inferior cava vein, and LS and SS measurements) composed the P-CC index (ranging 0-10 points). In 141 cases with repeated BT and US and TE measures, two groups which obtained a P-CC index of 0-4 or 5-10 points at basal-time evaluation, identified 89 cases with a low/moderate (HR 0.41; 95%CI 0.18-0.90) and 52 with high-risk profile of major events (i.e., need of REDO Fontan or OHT, and HCC onset or death) (HR 2.47; 95%CI 1.12-5.42) respectively at 6-years FU (p<0.03). During FU, 10 patients (6.7%) died, 3 received OHT (2.0%), and 6 had HCC onset (4.0%). Dynamic TE and NIT evaluation (APRI, FORNS, FIB-4, MELD-XI, FONLIVER, significantly predicted the liver disease progression and clinical outcomes, in fact at FU, around 20 percent of patients showed a worsening of parameters and a progression of P-CC index (all, p <0.01). Conclusions The P-CC index can predict risk patients with a-FALD and could help to follow the most advanced profiles in relation to the risk class defined by the new and simple P-CC index. These tools applied routinely could become very interesting on the personalized clinical management of patients with UH and Fontan circuit.Cavalletto_abstract