Publication Date
1-1-2024
Journal
Hepatology Communications
DOI
10.1097/HC9.0000000000000361
PMID
38180987
PMCID
PMC10781130
PubMedCentral® Posted Date
1-5-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Child, Humans, Alagille Syndrome, Biliary Atresia, Biomarkers, Growth Differentiation Factor 15, Non-alcoholic Fatty Liver Disease, Mitochondrial Diseases
Abstract
BACKGROUND: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children.
METHODS: Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls.
RESULTS: GDF15 levels compared to controls were mildly elevated in patients with α1-antitrypsin deficiency, Alagille syndrome, and biliary atresia-young subgroup, but markedly elevated in MH (p98th percentile of controls identified genetically confirmed MH with a sensitivity of 88% and specificity of 96%. In MH, independent predictors of survival without requiring liver transplantation were international normalized ratio and either GDF15 or FGF21 levels, with levels/L predicting survival without liver transplantation (p<0.01).
CONCLUSIONS: GDF15 and FGF21 are significantly higher in children with MH compared to other childhood liver diseases and controls and, when combined, were predictive of MH and had prognostic implications.
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