Fontan-associated Liver Disease Research Articles

Accuracy of elastography versus biopsy in assessing severity of liver fibrosis in young Fontan patients.

We performed a single-centre retrospective study comparing the accuracy of non-invasive elastography with liver biopsy in accurate assessment of Fontan-associated liver disease. Fontan patients who underwent combined assessment with a percutaneous liver biopsy and non-invasive elastography between January 2015 and December 2023 at our Children's hospital were included. Liver biopsies were classified using the Congestive Hepatic Fibrosis Score as early Fontan-associated liver disease (scores 1, 2) and advanced Fontan-associated liver disease (score 3/bridging fibrosis and score 4/cirrhosis). Elastography values were categorised as advanced Fontan-associated liver disease for liver elasticity >2.1 m/s by ultrasound and liver stiffness >5 KPa on magnetic resonance elastography. We included 130 patients (116 children, 89%, mean age at biopsy: 14.6 years ± 3.6) who underwent liver biopsy at a mean duration of 11.1 years (±0.3) following Fontan surgery. Advanced Fontan-associated liver disease was noted in 41 (31.5%) patients with 13 (10%) showing frank cirrhosis. Pre-biopsy ultrasound showed advanced liver fibrosis in 18/125 (14%), with low sensitivity (23%), high specificity (90%), and low accuracy (68%, k = 0.1) in diagnosing advanced Fontan-associated liver disease. Similarly, pre-biopsy magnetic resonance elastography showed advanced fibrosis in 23/86 (27%) of patients, with low sensitivity (30%), fair specificity (75%), and low accuracy (63%, k = 0.1). Interestingly, advanced Fontan-associated liver disease was missed by ultrasound in 29% and by magnetic resonance elastography in 25% of patients. Advanced Fontan-associated liver disease was associated with lower platelet count (p = 0.02) and higher Gamma-glutamyl Transferase levels (p = 0.02). Advanced hepatic fibrosis is common among paediatric Fontan patients. Non-invasive elastography may overestimate and underestimate the degree of liver fibrosis, and therefore, liver biopsy may be required for confirming disease severity.

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

The abnormal hemodynamics in Fontan circulation due to persistently increased systemic venous pressure results in hepatic venous congestion and Fontan-associated liver disease. Combined assessment of cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in this context have not been fully explored. To evaluate cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in patients who have undergone Fontan procedures. Thirty-eight patients and 23 controls underwent cardiac and liver MRI examinations in a 3.0-T scanner. Mann-Whitney, Fisher exact test, and Spearman's correlation were applied to evaluate myocardial volumes, function, native cardiac and liver T1 mapping, ECVs and liver stiffness. The mean native cardiac T1 value (p = 0.018), cardiac ECV (p < 0.001), liver native T1 (p < 0.001), liver ECV (p < 0.001), and liver stiffness (p < 0.001) were higher in patients than controls. The indexed end-diastolic volume (EDVi) correlated with the myocardial ECV (r = 0.356; p = 0.033), native liver T1 (r = 0.571; p < 0.001), and with liver stiffness (r = 0.391; p = 0.015). In addition, liver stiffness correlated with liver ECV (r = 0.361; p = 0.031) and native liver T1 (r = 0.458; p = 0.004). An association between cardiac remodeling and cardiac and liver fibrosis were found in this population. The usefulness of MRI to follow cardiac and liver involvement in these patients is critical to improve treatment strategies and to prevent the need for combined liver and heart transplantation.

A single-cell multiomics profile of Fontan-associated liver disease

A single-cell multiomics profile of Fontan-associated liver disease

Fontan-Associated Liver Disease and the Double Organ Transplant: Addressing the Heart of the Argument

Fontan-Associated Liver Disease and the Double Organ Transplant: Addressing the Heart of the Argument

Single-cell multiomics guided mechanistic understanding of Fontan-associated liver disease.

The Fontan operation is the current standard of care for single-ventricle congenital heart disease. Individuals with a Fontan circulation (FC) exhibit central venous hypertension and face life-threatening complications of hepatic fibrosis, known as Fontan-associated liver disease (FALD). The fundamental biology and mechanisms of FALD are little understood. Here, we generated a transcriptomic and epigenomic atlas of human FALD at single-cell resolution using multiomic snRNA-ATAC-seq. We found profound cell type-specific transcriptomic and epigenomic changes in FC livers. Central hepatocytes (cHep) exhibited the most substantial changes, featuring profound metabolic reprogramming. These cHep changes preceded substantial activation of hepatic stellate cells and liver fibrosis, suggesting cHep as a potential first "responder" in the pathogenesis of FALD. We also identified a network of ligand-receptor pairs that transmit signals from cHep to hepatic stellate cells, which may promote their activation and liver fibrosis. We further experimentally demonstrated that activins A and B promote fibrotic activation in vitro and identified mechanisms of activin A's transcriptional activation in FALD. Together, our single-cell transcriptomic and epigenomic atlas revealed mechanistic insights into the pathogenesis of FALD and may aid identification of potential therapeutic targets.

A multiple variable index and extracardiac-Fontan associated hepatic fibrosis

BackgroundThe serial follow-up of Fontan-associated liver disease is challenging, as laboratory values are frequently normal, especially with mild to moderate liver disease. ObjectiveWe investigated a composite index's correlation with hepatic biopsy total fibrosis scores in extracardiac Fontan patients. MethodsWe identified extracardiac Fontan patients undergoing cardiac catheterization and transvenous hepatic biopsies between June 2013 and September 2023 and liver shear wave elastography between January 2017 and July 2023. We developed a composite index from the following: 1) elastography values, 2) sex, 3) history of a neonatal aortopulmonary shunt for pulmonary flow obstruction, 4) pacemaker, 5) Fontan duration, 6) bilirubin values, 7) univentricular dysfunction, 8) atrioventricular valvar regurgitation, 9) mean Fontan pressures, and 10) venovenous collaterals presence. We correlated the index with hepatic total fibrosis scores (0–8), the sum of pathology grading (0 to 4) performed for sinusoidal and portal fibrosis. We defined a hepatic total fibrosis score of 0–3 as none to mild and 4–8 as moderate to severe fibrosis. ResultsWe identified 62 patients who underwent 92 transvenous liver biopsies, with 30 patients undergoing 2 biopsies. The average age at biopsy was 15 ± 2 years. We found a strong correlation (rho = 0.8, p = .00001) between liver total fibrosis scores and composite index values. A receiver operating characteristic analysis demonstrated that an index cut-off value of ≥26 predicted a total fibrosis score of ≥4 with a sensitivity of 71 % and a specificity of 75 % (AUC = 0.73, 95 % CI 0.63, 0.83, p = .0001). ConclusionsWe developed a composite index with a moderate predictive ability to discriminate none to mild from moderate to severe hepatic fibrosis. Nevertheless, additional data is needed to assist further validation and determine its clinical utility in the serial follow-up of Fontan associated liver disease.

Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study.

As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation. We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022. The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time>283 min (4.7h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis. Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

Epidemiology of Fontan-associated liver disease in Japan: Results from a nationwide survey in 2021.

Although the Fontan procedure has improved the survival of patients with single-ventricle heart disease, the long-term consequences of the procedure have been a concern. This study aimed to explore the patients' postoperative clinical characteristics, including a diagnosis of Fontan-associated liver disease (FALD). A nationwide Japanese epidemiological survey of post-Fontan patients was undertaken in 2021. The survey targets were selected from all departments of pediatrics, pediatric surgery, cardiology, cardiovascular surgery, and gastroenterology using stratified random sampling by the number of beds. Each department was asked to complete a mail-back questionnaire on the numbers of patients and their clinical characteristics. The diagnosis of FALD was made by each attending physician. The estimated number of post-Fontan patients was 7810 (95% confidence interval, 5430-10200) in 2020, with a period prevalence of 61.9 per million. During the follow-up of 13.8years after the Fontan procedure, 40% of patients were diagnosed with FALD. An elevated γ-glutamyl transpeptidase level was the most common finding leading to the FALD diagnosis (41%), and 45% of the patients also showed liver fibrosis. Compared with non-FALD patients, FALD patients were older, had longer duration since the Fontan procedure, and had more severe cardiac or liver conditions. However, more than half of the non-FALD patients had elevated liver enzyme levels, suggesting underestimation of the number of FALD patients. In 2020, approximately 40% of post-Fontan patients underwent follow-up with a diagnosis of FALD, although the lack of established diagnostic criteria for FALD could affect the reported prevalence of FALD.

Fontan-Associated Liver Disease: A Review.

Fontan-associated liver disease (FALD) is a chronic complication of the Fontan procedure, a palliative surgery for patients with congenital heart disease that results in a single-ventricle circulation. The success of the Fontan procedure has led to a growing population of post-Fontan patients living well into adulthood. For this population, FALD is a major cause of morbidity and mortality. It encompasses a spectrum of hepatic abnormalities, ranging from mild fibrosis to cirrhosis and hepatocellular carcinoma. The pathophysiology of FALD is multifactorial, involving hemodynamic and inflammatory factors. The diagnosis and monitoring of FALD present many challenges. Conventional noninvasive tests that use liver stiffness as a surrogate marker of fibrosis are unreliable in FALD, where liver stiffness is also a result of congestion due to the Fontan circulation. Even invasive tissue sampling is inconsistent due to the patchy distribution of fibrosis. FALD is also associated with both benign and malignant liver lesions, which may exhibit similar imaging features. There is therefore a need for validated diagnostic and surveillance protocols to address these challenges. The definitive treatment of end-stage FALD is also a subject of controversy. Both isolated heart transplantation and combined heart-liver transplantation have been employed, with the latter becoming increasingly preferred in the US. This article reviews the current literature on the epidemiology, pathophysiology, diagnosis, and management of FALD, and highlights knowledge gaps that require further research.

Shear-wave elastography for monitoring Fontan-associated liver disease: A prospective cohort study.

The spectrum of Fontan-associated liver disease (FALD) varies from abnormal liver function tests to fibrosis and even cirrhosis. In this prospective study, we evaluated the role of shear-wave elastography (SWE) in predicting the presence of advanced FALD. Forty-eight patients (30 males, 13.9 [6-21] years) with a Fontan circulation were evaluated at 8.3 (2.1-18.7) years since the Fontan surgery. The median liver stiffness measurement (LSM) value was higher than values in normal children at 15.4 (9.5-38.7) kPa. The LSMs had a weak but significant correlation with age at the time of LSM (r = 0.25, p = 0.01) and duration post-Fontan surgery (r = 0.31, p = 0.02). It had a poor correlation with the concomitant aspartate transaminase-to-platelet ratio index (r = 0.1, p = 0.39). No difference in the elastography values between children with and without ultrasound evidence of advanced liver disease (17.7 [interquartile range, IQR: 4] vs. 16.1 [IQR: 6], p = 0.62] was observed. Further studies are required to determine the precise role of SWE as a noninvasive marker of liver fibrosis in FALD.

"Fontan Conduit Stent-Angioplasty and Progression of Fontan-Associated Liver Disease".

Patients with Fontan circulation insidiously develop congestive hepatopathy related to chronically reduced cardiac output and central venous hypertension, also known as Fontan-associated liver disease (FALD). Fontan pathway obstruction is increasingly detected and may accelerate FALD. The impact of conduit stent angioplasty on FALD is unknown. Retrospective, single-center review of patients with Fontan circulation who underwent conduit stent angioplasty at cardiac catheterization over 5-year period. Demographics and cardiac histories were reviewed. Labs, liver ultrasound elastography, echocardiogram, hemodynamic and angiographic data at catheterization were recorded pre- and post-stent angioplasty. Primary outcome was change in hepatic function via MELD-XI scores and liver stiffness (kPa), with secondary outcomes of ventricular function, BNP, and repeat catheterization hemodynamics. 33 patients underwent Fontan conduit stent angioplasty, 19.3 ± 7.0years from Fontan operation. Original conduit diameter was 19.1 ± 1.9mm. Prior to angioplasty, conduit size was reduced to a cross-sectional area 132 (91, 173)mm2 and increased to 314 (255, 363)mm2 post-stent. Subjects' baseline median MELD-XI of 11 (9, 12) increased to 12 (9, 13) at 19 ± 15.5months post-angioplasty (n = 22, p = 0.053). There was no significant change in liver stiffness at 12.1 ± 8.9months post-angioplasty (n = 15, p = 0.13). Median total bilirubin significantly increased (1.4 [0.9, 1.8]), from baseline 1.1 [0.7, 1.5], p = 0.04), as did median BNP (41 [0, 148] from baseline 34 [15, 79]; p = 0.02). There were no significant changes in ventricular function or repeat invasive hemodynamics (n = 8 subjects). Mid-term follow-up of Fontan subjects post-conduit stent angioplasty did not show improvements in non-invasive markers of FALD.

Achieving Consensus: Severity-Graded Definitions of Fontan-Associated Complications to Characterize Fontan Circulatory Failure

BackgroundFontan physiology leads to chronic changes in other organ systems that may affect long-term survival and the success of heart transplantation. Inadequate assessment and treatment of the extra-cardiac effects of Fontan may contribute to poor outcomes. Severity-graded/ordinal consensus definitions of Fontan complications are lacking, which limits understanding of how Fontan-specific morbidity affects patients’ outcomes. Methods and ResultsA panel of Fontan patient and physiology experts, including pediatric, adult congenital, heart failure, and critical-care cardiology as well as pediatric nephrology, hepatology and psychology, convened to develop definitions of Fontan complications. Definitions were created by using a severity-graded ordinal scale: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, disabling or life threatening. Following definition creation, a second panel of 21 experts in Fontan circulatory failure used a modified Delphi methodology to modify and vote on definitions until consensus (> 90% agreement without recommended further modification) was reached on final definitions. After 3 rounds of modifications and voting, consensus agreement was achieved on all Fontan-specific definitions. The defined complications and morbidities of Fontan include: anatomic Fontan pathway obstruction, cyanosis, systemic venous abnormalities resulting from venous insufficiency, atrial arrhythmia, ventricular arrhythmia, bradycardia, chronic pleural effusions, chronic ascites, protein-losing enteropathy, plastic bronchitis, hemoptysis and pulmonary hemorrhage, sleep apnea, Fontan-associated liver disease, portal and hepatic variceal disease, acute kidney injury affecting clinical treatment, polycythemia, thrombotic disease, recurrent or severe bacterial infection, skin atrophy, adrenal insufficiency, physical impact of previous stroke, mood/behavior disorder, and neurodevelopmental disorder. ConclusionConsensus and severity-graded definitions of Fontan-specific cardiac and extra-cardiac complications were achieved and are available for use in research. They will allow future robust analyses of Fontan patient outcomes.

Intrahepatic Transcriptomics Differentiate Advanced Fibrosis and Clinical Outcomes in Adults With Fontan Circulation

BackgroundThe molecular mechanisms underlying Fontan-associated liver disease (FALD) remain largely unknown. ObjectivesThis study aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. MethodsThis retrospective cohort study included adults with the Fontan circulation. Baseline clinical, laboratory, imaging, and hemodynamic data as well as a composite clinical outcome (CCO) were extracted from medical records. Patients were classified into early or advanced fibrosis. RNA was isolated from formalin-fixed paraffin-embedded liver biopsy samples; RNA libraries were constructed with the use of an rRNA depletion method and sequenced on an Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were performed with the use of DESeq2 and Metascape. ResultsA total of 106 patients (48% male, median age 31 years [IQR: 11.3 years]) were included. Those with advanced fibrosis had higher B-type natriuretic peptide levels and Fontan, mean pulmonary artery, and capillary wedge pressures. The CCO was present in 23 patients (22%) and was not predicted by advanced liver fibrosis, right ventricular morphology, presence of aortopulmonary collaterals, or Fontan pressures on multivariable analysis. Samples with advanced fibrosis had 228 upregulated genes compared with early fibrosis. Samples with the CCO had 894 upregulated genes compared with those without the CCO. A total of 136 upregulated genes were identified in both comparisons and were enriched in cellular response to cytokine stimulus or oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-β signaling pathway, and vasculature development. ConclusionsPatients with FALD and advanced fibrosis or the CCO exhibited upregulated genes related to inflammation, congestion, and angiogenesis.

Histopathological Spectrum and Molecular Characterization of Liver Tumors in the Setting of Fontan-Associated Liver Disease.

Univentricular heart is corrected with the Fontan procedure (FP). In the long term, so-called Fontan-associated liver diseases (FALDs) can develop. The aim of this study is to analyze the molecular profile of FALDs. FALDs between January 1990 and December 2022 were reviewed for histology and immunohistochemistry, laboratory data, and images. Targeted next generation sequencing (NGS), performed on the DNA and RNA of both neoplastic and non-lesional liver tissue, was applied. A total of 31/208 nodules > 1 cm in diameter were identified on imaging, but a liver biopsy was available for five patient demonstrating the following: one hepatocellular adenoma (HA), two hepatocellular carcinomas (HCCs), one fibrolamellar carcinoma (FLC), and one intrahepatic cholangiocarcinoma (ICC). Molecular analysis showed a copy number alteration involving FGFR3 in three cases (two HCCs and one ICC) as well as one HCC with a hotspot mutation on the CTNNB1 and NRAS genes. Tumor mutational burden ranged from low to intermediate. A variant of uncertain significance in GNAS was present in two HCCs and in one ICC. The same molecular profile was observed in a non-lesional liver. A DNAJB1-PRKACA fusion was detected only in one FLC. Neoplastic FALDs show some unusual molecular profiles compared with non-Fontan ones. The presence of the same alterations in non-lesional cardiac cirrhosis could contribute to the development of FALD.

Percutaneous Liver Biopsy Adverse Events in Stable Fontan Patients

Background:In patients who have undergone a Fontan operation, altered cardiac circulation can lead to several organ pathologies, including Fontan-associated liver disease. Transjugular liver biopsies are the standard for assessing liver disease in these patients, however data for a percutaneous approach in these patients is limited. Percutaneous liver biopsies are the preferred method in the general population. The objective of this study was to compare the rate of adverse events for percutaneous liver biopsies in Fontan patients to the general pediatric population.&#x0D; Methods:A retrospective chart review was conducted on percutaneous liver biopsy patients over a five-year period. For each patient, a 90-day period post-biopsy was investigated to look for any indications of adverse events (pain, hemorrhage) and related work-up (imaging, hospital admission), scoring the severity of these events based on SIR adverse event classification. Patients were stratified based on if they underwent a cardiac catheterization procedure immediately prior to biopsy or not.&#x0D; Results:A total of 412 biopsies were reviewed, 367 without cardiac catheterization and 45 with catheterization. Across the entire population, 38 adverse events were found, giving an overall adverse event rate of 9.2%. Comparing populations, non-catheterized patients were found to have an adverse event rate of 9.0%, with a minor rate of 7.2% and a major rate of 1.8%. The catheterized group had an adverse event rate of 11.1%, with a minor rate of 8.8% and a major rate of 2.3%. There were no lethal events. These rates align with reported literature.&#x0D; Conclusion and Potential Impact:There was no significant difference in adverse event rates between Fontan patients and the general population after a percutaneous liver biopsy. This information can guide clinical decisions, as these biopsies are cheaper, less invasive, and do not expose patients to ionizing radiation.

Serum level of full-length connective tissue growth factor reflects liver fibrosis stage in patients with Fontan-associated liver disease.

Chronic liver disease leads to liver fibrosis, and an accurate diagnosis of the fibrosis stage is crucial for medical management. Connective tissue growth factor (CTGF) is produced by endothelial cells and platelets and plays a central role in inducing fibrosis in various organs. In the present study, we tested the validity of measuring the serum levels of two types of CTGF to estimate the biopsy-confirmed liver fibrosis stage. We used two detection antibodies targeting the N- and C-terminal of CTGF to measure the serum levels of two forms of CTGF consisting of its full length and its N-terminal fragment. We analyzed the level of CTGF (via enzyme-linked immunosorbent assay) and the liver fibrosis stage in 38 patients with Fontan-associated liver disease (FALD) (26 cases of which were diagnosed pathologically). Correlations were determined by multivariate analysis and the area under the receiver operating characteristic curve. The 65 patients with nonalcoholic fatty liver disease (NAFLD) were included as a disease control group for examination. Full-length CTGF was significantly inversely correlated with liver fibrosis in patients with FALD. Although the platelet count was also associated with the liver fibrosis stage, full-length CTGF was more closely correlated with the fibrosis stage. Furthermore, the level of full-length CTGF was inversely associated with high central venous pressure. Conversely, the serum level of CTGF was not correlated with the fibrosis stage in NAFLD. The serum level of full-length CTGF may be useful for estimating the liver fibrosis stage in patients with FALD.

Fontan Associated Liver Disease (FALD) - When Should We Consider Combined Heart-lung Transplant

Fontan Associated Liver Disease (FALD) - When Should We Consider Combined Heart-lung Transplant

Biomarkers of fibrosis and portal hypertension in Fontan-associated liver disease in children and adults

BackgroundFontan-associated liver disease (FALD) refers to structural and functional changes of the liver caused by the physiology of the Fontan palliation. Currently, liver biopsy is the gold standard to assess liver fibrosis of FALD. AimInvestigate biomarkers correlating with severity of liver biopsy fibrosis in FALD. MethodsA retrospective study of post-Fontan patients ≥ 10 years of age who underwent liver biopsy was conducted. Advanced liver disease (ALD) was defined as bridging fibrosis and/or cirrhosis on liver biopsy. AST-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4) and Liver Stiffness Measurement (LSM) from FibroScan were used as non-invasive fibrosis scores. ResultsSixty-six patients (26/47; 55.3% adults and 13/19 children; 68.4%) had ALD on biopsy. ALD was associated with lower platelet count (151 vs. 198 K/uL, p = 0.003), higher APRI (0.64 vs. 0.32, p = 0.01), higher FIB-4 (0.64 vs. 0.32, p = 0.02). Liver fibrosis score correlated with APRI (0.34, p = 0.02) and FIB-4 (0.47, p = 0.001) in adults. LSM had a high sensitivity at 81.3% with 45.5% specificity at a cut-off 18.5 kPa. ConclusionsAPRI and FIB-4 had modest discrimination to identify adults with advanced liver disease, but not children, indicating that these values may be followed as a marker of FALD progression in older patients.

A surveillance for advanced liver disease and characterization of hyperechogenic lesions after Fontan surgery in a prospective cohort of cases with congenital univentricular heart

Abstract Background The congenital univentricular heart (UH) is a rare disease corrected with the palliative Fontan’s intervention, that restores the survival of most child and young patients up to adultwood. Unlikely, these patients develop a series of complications, among all, the Fontan associated liver disease (FALD), that causes the occurrence of liver cirrhosis and hepatocellular carcinoma (HCC), that negatively impacts the life expectancy in the majority of cases. Purpose Our primary aim was to identify the presence of severe FALD in our patients by liver fibrosis and portal hypertension scores (FORNS, liver and spleen-platelet score or LSPS and SSPS), and by liver (LS) and spleen (SS) stiffness measurement in relation to time since Fontan, and secondarly to characterize all the abdominal-US hyperechogenic lesions (US-HL) according to the LI-RADS (LR) CT/MRI categories. Method One-hundred-46 outpatients (83 m/63 f, aged 25,2±11.0 yrs) born with UH corrected with Fontan circuit have been recruited prospectively from 2019 to 2023 (FUmean 24.5±15.1 mos). Each patient underwent a complete clinical history and instrumental examination, by imaging obtained with US, CT and MRI, a specific lab-test profile, and the LS and SS evaluation by transient elastography (VCTE, Fibroscan). ROC curves were built to select the scores cut-off proved to be the most accurate to diagnose and grade FALD. Based on the presence of US-HL found in 43 cases (29,5%), we grouped: 23 cases with LR-1 or 2 (benign), 15 with LR-3 (suspect) and 5 with LR-4 or 5 (malign). Results Features for definition of failing-Fontan appeared in 17.5%, 47.5% and 80% of cases with &amp;lt;15; 15-25 or &amp;gt;25yrs since Fontan surgery, respectively (p&amp;lt;0.01). All the scores used (FORNS with cut-off ≥4, LSPS ≥1.4, SSPS ≥2.3, LS ≥20.2 and SS ≥30.7) showed high sensitivity and specificity, improving FALD diagnostic accuracy and staging (all p&amp;lt;0.001). Moreover by identification of selective criteria related to advanced liver disease and portal hypertension, we applied a novel risk-score for failing-Fontan, that predicted a low-moderate risk profile (HR 0.30;CI 0.18-0.52) in 72 patients and a high risk profile (HR 3,29,CI 1.93-5.60) in 74 (51%). During FU, 13 patients (8.9%) died, 5 received OHT (3.4%) and 5 had HCC occurrence (3.4%). Finally, cases with US-HL stratified by classes LR-3-4-5 (20 cases, 46.5%) appeared significantly associated with a more advanced FALD (16/4, 75% vs. 68/58, 46%; p=0,004) and a longer time since Fontan (26.3±9.4 vs. 19.8±10.8; p=0,025). Conclusion The novel risk score proposed may help to predict the development of cirrhosis in high risk patients and focussed on the need for surveillance by imaging methods to characterized the US-HL, that appeared at risk of malignity (nodule size &amp;gt;20mm and/or presence of wash-out into portal-hepatocellular phase or into LR ≥3 classes).

Adult patients with univentricular physiology after Fontan palliation: prevalence and percutaneous closure of veno-venous collaterals

Abstract Background The Fontan operation resulted in improved survival of patients with congenital heart defects not equipped to sustain a biventricular circulation. Long-term complications are common. Veno-venous collaterals (VVC) can have both potentially beneficial and adverse physiological effects. The aim of this study was to evaluate the prevalence of VVC in adult Fontan patients and describe the percutaneous treatment strategy and the short term follow-up. Methods In this single-centre retrospective observational cohort study, consecutive adult Fontan patients under follow-up in the period between 2017-2023 were included. Results From a cohort of 51 Fontan patients, 14 (28%) underwent a percutaneous closure of VVC (71% female, mean age at intervention 24±4 years). Mean follow-up duration was 2.2±1.1 years. Indications were symptoms and/or significant exercise-related hypoxia. Ten patients (71%) had a systemic left ventricle, and 79% had an extracardiac tunnel (median conduit size 16[16-20]mm). Mean Fontan pressure was 10±4mmHg. Seven patients (50%) had Fontan-associated liver disease. A total of 24 VVC were occluded using coils and/or vascular plugs. No periprocedural complications occurred. The VVC originated from right-sided tributaries of the vena cava inferior (36%), superior vena cava (28%) or both (36%), with the majority draining directly into the pulmonary venous circulation. Eight patients (57%) reported a reduction of symptoms. Mean saturation in rest improved significantly, yet saturation during maximal exercise remained unchanged (94±3 to 97±3%, p=0.002 and 88±3 to 91±4%, p=0.103, respectively). Conclusions VVC are highly prevalent in the adult Fontan population and typically connect the right-sided tributaries of the vena cava inferior and/or superior with the pulmonary veins. Low Fontan pressures do not exclude the presence of VVC. Percutaneous closure of VVC is technically feasible and safe and is associated with reduction of symptoms and a significant rise in resting peripheral oxygen saturation. These results warrant further studies.