Non-invasive assessment of liver abnormalities in pediatric Fontan patients

Abstract

Liver abnormalities are well known among long-term survivors of Fontan palliation, which remains the definite surgery for complex congenital heart disease and single ventricle physiology. Pediatric data however are scarce. We assessed the prevalence and degree of liver abnormalities in pediatric Fontan patients through non-invasive investigations suitable for longitudinal follow-up. Thirty-five patients with a median age of 11.8 years (5.2-16.6) and median time since Fontan of 6 years (1.17-13.83) were studied. Each child underwent a blood test, liver Doppler ultrasound (US), and transient elastography (TE). Healthy children were used as controls for TE measurement. AST, ALT, γGT, and direct bilirubin were abnormal in respectively 12 (34%), 5 (14%), 24 (69%), and 7 (20%) patients, while platelet count was decreased in 7 (20%). Splenomegaly was present in 7 (20%) patients. Portal vein mean flow velocity was < 15 cm/s in 19 (54%) patients indicative of portal hypertension. Twenty-two patients (63%) showed inferior vena cava collapsibility index values below 17%, indicating venous congestion. Hepatic artery and superior mesenteric artery resistance index were inversely correlated with time post Fontan (p < 0.05). TE values in Fontan patients were significantly higher than controls, with a median of 12.6 versus 4.6 kPa (p < 0.001) and were already increased shortly after Fontan completion.Conclusion: Liver abnormalities are frequently observed in pediatric Fontan patients. The non-invasive investigations used were not able to confirm liver fibrosis or differentiate hepatic congestion from fibrosis. Based on our findings, we propose a prospective screening protocol with serial measurements of laboratory, (Doppler) US, and TE parameters. What is Known:• Hepatic dysfunction is a well-known consequence of the Fontan circulation. • The natural history of Fontan-associated liver disease in the pediatric age group remains unclear. What is New: • Liver abnormalities are frequently observed in pediatric Fontan patients; however, differentiating liver fibrosis and hepatic congestion with non-invasive investigations remains challenging. Sonographic Doppler measurements may improve our insight in both Fontan-associated liver disease development and the functioning of the Fontan circulation. • A prospective screening protocol is proposed to improve our ability to detect Fontan-associated liver disease early on and understand its natural history. Keywords Fontan • Liver • Fontan-associated liver disease • Children • Non-invasive assessment Abbreviations AFP Alpha-fetoprotein ALT Alanine aminotransferase ALP Alkaline phosphatase AST Aspartate aminotransferase CK Creatine kinase DI Dampening index FALD Fontan-associated liver disease GGT Gamma-glutamyl transferase HA Hepatic artery HCC Hepatocellular carcinoma HV Hepatic veins Communicated by Peter de Winter

Risk factors for Fontan-associated hepatocellular carcinoma

“…De Bruyne et al [24] reported that the aspartate aminotransferase, alanine transaminase, gamma-glutamyl transferase, and direct bilirubin levels were increased in 12 (34%), 5 (14%), 24 (69%), and 7 (20%) Fontan patients, respectively; the platelet count was decreased in 7 (20%) Fontan patients. Here, we found that the T-BIL level tended to be increased in FALD-HCC patients; it was a useful predictor of FALD-HCC.…”

Meta‐analysis: Incidence of cirrhosis and hepatocellular carcinoma in patients with Fontan palliation

“…This provided us an accurate estimate of the number of patients with cirrhosis, since liver biopsy is considered the gold standard. While non‐invasive methods to detect liver fibrosis and cirrhosis are available, their utility in patients post Fontan surgery remains under investigation, with liver biopsy still the most accurate way for diagnosis of cirrhosis in this patient population 29,59–61 . For HCC, we only included cases where HCC was diagnosed histologically, since Liver Imaging Reporting and Data System (LI‐RADS) criteria used for image‐based HCC diagnosis were developed for patients with cirrhosis and chronic HBV and have not been validated in Fontan patients 62 .…”

Noninvasive Pediatric Liver Fibrosis Measurement: Two-Dimensional Shear Wave Elastography Compared With Transient Elastography

“…Another potential bias is our cohort's subgroup of patients with FALD. Hepatic congestion increases TE values, which could be falsely attributed to fibrosis ( 37 , 38 ). To address this bias, we performed a sensitivity analysis and confirmed the absence of significant differences after excluding 13 children with FALD.…”