Paediatric fatty liver disease (PeFLD): All is not NAFLD – Pathophysiological insights and approach to management  Robert Hegarty, Maesha Deheragoda, Emer Fitzpatrick, Anil Dhawan  Journal of Hepatology  Volume 68, Issue 6, Pages 1286-1299 (June 2018) DOI: 10.1016/j.jhep.2018.02.006 Copyright © 2018 Terms and Conditions

Journal of Hepatology 2018 68, 1286-1299DOI: (10. 1016/j. jhep. 2018 Copyright © 2018 Terms and Conditions

Fig. 1 Paediatric fatty liver disease: disorders to consider and investigational approach according to patient phenotype. Journal of Hepatology 2018 68, 1286-1299DOI: (10.1016/j.jhep.2018.02.006) Copyright © 2018 Terms and Conditions

Fig. 2 Schematic representation of the mitochondria and other organelle dysfunction leading to the accumulation of fat droplets. A1AT-D, alpha 1-antitrypsin deficiency; ACAD9, acyl-CoA dehydrogenase 9; AT, ataxia telangiectasia; CACT, carnitine-acylcarnitine translocase; CPS1, carbamoylphosphate synthetase I; CDG, congenital disorder of glycosylation; CPT1, carnitine palmitoyltransferase 1; CPT2, carnitine palmitoyltransferase 2; DLD, dihydrolipoamide dehydrogenase deficiency; GSD, glycogen storage disease; HFI, hereditary fructose intolerance; LCHAD, long-chain acyl-CoA dehydrogenase; LPI, lysinuric protein intolerance; LAL-D, lysosomal acid lipase deficiency; MCAD, medium chain acyl-CoA dehydrogenase; MD, muscular dystrophy; NAFLD, non-alcoholic fatty liver disease; NBAS, neuroblastoma amplification sequence; NPC, Niemann-Pick C; OA, organic acidemia; OTC, ornithine transcarbamylase deficiency; VLCHAD, very long-chain acyl-CoA dehydrogenase; WRS, Wolcott Rallison syndrome. Journal of Hepatology 2018 68, 1286-1299DOI: (10.1016/j.jhep.2018.02.006) Copyright © 2018 Terms and Conditions

Fig. 3 Balancing the contributions of fat: risk factors to consider when trying to understand the aetiologies of steatosis. ALF, acute liver failure; BMI, body mass index; DM, diabetes mellitus; IR, insulin resistance; NAFLD, non-alcoholic fatty liver disease. Journal of Hepatology 2018 68, 1286-1299DOI: (10.1016/j.jhep.2018.02.006) Copyright © 2018 Terms and Conditions

Fig. 4 Patterns of steatosis in mitochondrial hepatopathy, tyrosinemia type 1, glycogen storage disorder type 1a and lysosomal acid lipase deficiency. (A) Mitochondrial disorders can demonstrate varying degrees of steatosis (microvesicular steatosis indicated by the short arrows, macrovesicular steatosis demonstrated by the long arrows, H&E ×200 magnification). (B) Tyrosinemia type I in a 6-month child with mixed macro- and microvesicular steatosis (microvesicular steatosis indicated by the short arrows, H&E ×200 magnification). (C) Liver biopsy from an 18-month old child with glycogen storage disease type 1a showing severe predominantly microvesicular steatosis admixed with glycogen (H&E ×400 magnification. Inset shows microvesicular steatosis, short arrows, within hepatocytes at ultrastructural level). (D) A liver biopsy from a nine-year old child with lysosomal acid lipase deficiency, demonstrating severe microvesicular steatosis (H&E ×400 magnification). The inset shows cholesteryl ester storage material within Kupffer cells (Inset D, short arrows, Diastase Periodic Acid-Schiff ×400 magnification). Journal of Hepatology 2018 68, 1286-1299DOI: (10.1016/j.jhep.2018.02.006) Copyright © 2018 Terms and Conditions