Dataset Information

Spectrum of Fontan-associated liver disease assessed by MRI and US in young adolescents.

ABSTRACT:

Purpose

Patients with Fontan circulation are at risk of developing hepatic fibrosis/cirrhosis. The mechanisms and disease development are unclear and early secondary liver cancer is a concern. This study will describe hepatic imaging findings in a national cohort of adolescents with Fontan circulation.

Methods

The patients prospectively underwent abdominal contrast enhanced magnetic resonance imaging (MRI) including diffusion-weighted imaging. Images were assessed for criteria of fibrosis/cirrhosis including characterization of hepatic nodules. These nodules were in addition, assessed by ultrasonography (US). Nodules ≥ 1 cm were investigated and monitored to evaluate malignant transformation. Clinical and hepatic serological data were recorded.

Results

Forty-six patients, median age of 16.5 years (15.4-17.9 years) were enrolled. All patients underwent US examination and MRI was performed in 35/46 patients. On MRI, 60% had hepatomegaly and 37% had signs of fibrosis/cirrhosis. Seven patients had together 13 nodules ≥ 1 cm in diameter. Only 4/13 (17%) where seen on US. Nodules had variable MRI signal characteristics including hepatobiliary contrast enhancement and two nodules revealed portal venous phase 'wash-out' on the first examination. No further imaging signs of malignancy were revealed during the follow-up period of median 24.4 (7-42) months.

Conclusion

The majority of adolescents with Fontan circulation had imaging findings of fibrosis/cirrhosis of varying severity. US had low detection rate of hepatic nodules compared to MRI. The imaging work-up before transition to adult cardiology care did not reveal findings suggestive of malignancy. However, the high prevalence of Fontan-associated liver disease calls for surveillance strategies even in childhood.

SUBMITTER: Thrane KJ

PROVIDER: S-EPMC8215034 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Information is evolving on liver disease in pediatric patients with Fontan physiology. The purpose of this investigation is to evaluate the spectrum of liver disease in a pediatric population of patients with Fontan physiology and evaluate transient elastography (TE) as a noninvasive marker of liver disease. Methods and Results We prospectively enrolled all children with Fontan physiology. All patients underwent comprehensive liver evaluation including liver enzymes (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase), aspartate transaminase to platelet ratio index, albumin, bilirubin, international normalized ratio, complete blood cell count, abdominal ultrasound, and TE. Transjugular liver biopsies and hemodynamic measurements were performed in a subset of patients. A total of 76 children (median, 11.7; interquartile range, 8.4-14.8 [56% male]) were evaluated, with 17 having a transjugular liver biopsy (median 14.8 years; interquartile range, 14.3-17.4). All biopsies showed pathological changes. The severity of liver pathology did not correlate with TE. There was a positive correlation between TE and time since Fontan (R=0.42, P<0.01), aspartate transaminase to platelet ratio index (R=0.29, P=0.02), aspartate transaminase (R=-0.42, P<0.01), and platelets (R=-0.42, P<0.01). Splenomegaly on abdominal ultrasound was correlated with TE (z=-2.2, P=0.03), low platelet count (z=1.9, P=0.05), low aspartate transaminase (z=1.9, P=0.02), and low alkaline phosphatase (z=2.4, P=0.02). Conclusions Liver disease was ubiquitous in our cohort of pediatric patients with Fontan Physiology. Given the correlation between TE and time from Fontan, TE shows potential as a prospective marker of liver pathology. However, individual measurements with TE do not correlate with the severity of pathology. Given the prevalence of liver disease in this population, protective measures of liver health as well as routine liver health surveillance should be implemented with consideration for hepatology consultation and biopsy in the event of abnormal liver biochemical markers or imaging.

Project description:Background & aimsFontan-associated liver disease (FALD) has emerged as an important morbidity following surgical palliation of single ventricle congenital heart disease. In this study, non-invasive biomarkers that may be associated with severity of FALD were explored.MethodsA retrospective cohort of paediatric patients post-Fontan who underwent liver biopsy at a high volume at a paediatric congenital heart disease centre was reviewed.ResultsAmong 106 patients, 66% were male and 69% were Hispanic. The mean age was 14.4 ± 3.5 years, and biopsy was performed 10.8 ± 3.6 years post-Fontan. The mean BMI was 20.8 ± 5 kg/m2, with 27.4% meeting obesity criteria. Bridging fibrosis was observed in 35% of patients, and 10.4% of all patients had superimposed steatosis. Bridging fibrosis was associated with lower platelet counts (168.3 ± 58.4 vs. 203.9 ± 65.8 K/μl for congestive hepatic fibrosis score [CHFS] 0-2b, p = 0.009), higher bilirubin (1.7 ± 2.2 vs. 0.9 ± 0.7 mg/dl, p = 0.0090), higher aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] scores (APRI: 0.5 ± 0.3 vs. 0.4 ± 0.1, p <0.01 [AUC: 0.69] and FIB-4: 0.6 ± 0.4 vs. 0.4 ± 0.2, p <0.01 [AUC: 0.69]), and worse overall survival (median 2 years follow-up post-biopsy, p = 0.027). Regression modelling of temporal changes in platelet counts before and after biopsy correlated with fibrosis severity (p = 0.005).ConclusionsIn this large, relatively homogeneous adolescent population in terms of age, ethnicity, and Fontan duration, bridging fibrosis was observed in 35% of patients within the first decade post-Fontan. Bridging fibrosis was associated with worse survival. Changes in platelet counts, even years before biopsy, and APRI/FIB-4 scores had modest discriminatory power in identifying patients with advanced fibrosis. Steatosis may represent an additional risk factor for disease progression in obese patients. Further prospective studies are necessary to develop strategies to screen for FALD in the adolescent population.Lay summaryIn this study, the prevalence of Fontan-associated liver disease (FALD) in the young adult population and clinical variables that may be predictive of fibrosis severity or adverse outcomes were explored. Several lab-based, non-invasive markers of bridging fibrosis in FALD were identified, suggesting that these values may be followed as a prognostic biomarker for FALD progression in the adolescent population.

Project description:Background Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocholesterolemia secondary to Fontan-associated liver disease or inflammation. We investigated circulating lipids in adults with a Fontan circulation and assessed the associations with clinical characteristics and adverse events. Methods and Results We enrolled 164 outpatients with a Fontan circulation, aged ≥18 years, in the Boston Adult Congenital Heart Disease Biobank and compared them with 81 healthy controls. The outcome was a combined outcome of nonelective cardiovascular hospitalization or death. Participants with a Fontan (median age, 30.3 [interquartile range, 22.8-34.3 years], 42% women) had lower total cholesterol (149.0±30.1 mg/dL versus 190.8±41.4 mg/dL, P<0.0001), low-density lipoprotein cholesterol (82.5±25.4 mg/dL versus 102.0±34.7 mg/dL, P<0.0001), and high-density lipoprotein cholesterol (42.8±12.2 mg/dL versus 64.1±16.9 mg/dL, P<0.0001) than controls. In those with a Fontan, high-density lipoprotein cholesterol was inversely correlated with body mass index (r=-0.30, P<0.0001), high-sensitivity C-reactive protein (r=-0.27, P=0.0006), and alanine aminotransferase (r=-0.18, P=0.02) but not with other liver disease markers. Lower high-density lipoprotein cholesterol was independently associated with greater hazard for the combined outcome adjusting for age, sex, body mass index, and functional class (hazard ratio [HR] per decrease of 10 mg/dL, 1.37; 95% CI, 1.04-1.81 [P=0.03]). This relationship was attenuated when log high-sensitivity C-reactive protein was added to the model (HR, 1.26; 95% CI, 0.95-1.67 [P=0.10]). Total cholesterol, low-density lipoprotein cholesterol, and triglycerides were not associated with the combined outcome. Conclusions The Fontan circulation is associated with decreased cholesterol levels, and lower high-density lipoprotein cholesterol is associated with adverse outcomes. This association may be driven by inflammation. Further studies are needed to understand the relationship between the severity of Fontan-associated liver disease and lipid metabolism.