Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

Table 1 Non-invasive diagnostic tests of non-alcoholic fatty liver disease

Hepatic fibrosis scores	Advanced biochemical markers	Newly proposed markers
AST/ALT ratio	Cytokeratin 18 fragment levels (CK-18)	Serum potassium
Platelet ratio index (APRI)	Extracellular matrix turnover biomarkers:	Soluble Fas and Fas Ligand (sFasL)
Fibrosis (FIB)-4 index	Enhanced liver fibrosis (ELF) test	Plasma catepsin D (CatD)
NAFLD Fibrosis score (NFS)	Amino-terminal propeptide III procollagen (PIIINP)	Circulating zonulin
Pediatric NAFLD fibrosis score	Hyaluronic acid (HA)	Adipokines (e.g., chemerin)
		Serum Uric Acid (UA)
		Vitamin D
		Proteomics signature
		Metabolomic signature

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; NAFLD: Non-alcoholic fatty liver disease.

Table 2 Fatty liver disease: selection of possible causes in children and adolescents[41]

General or systemic	Genetic-metabolic causes	Drugs/chemicals
Anorexia nervosa (± refeeding)	α- and β-oxidation defects	Corticosteroids
Celiac disease	Abeta or hypobetalipoproteinemia	Diltiazem
Diabetes mellitus type 1	Alpha 1 -antitrypsin deficiency	Ecstasy, Cocaine, Solvents
Hepatitis C	Cholesterol ester storage disease/LAL	Estrogens
Hypothalamic–pituitary disorders	Citrin deficiency	Ethanol
Inflammatory bowel disease	Congenital disorders of glycosylation	Methotrexate
Obesity/Metabolic syndrome	Cystic fibrosis/Shwachman syndrome	Nifedipine
Obstructive sleep apnea	Familial hyperlipoproteinemias	Pesticides
Polycystic ovary syndrome	Glycogen storage disease (I, VI and IX)	Prednisolone
Protein calorie malnutrition	Hereditary Fructose Intolerance	Solvents
Rapid weight loss	Lipodystrophy	Valproate
Small intestine bacterial overgrowth	Mitochondrial and peroxisomal defects	Vitamin A
Thyroid disorders	Organic acidosis	Zidovudine and HIV treatments
	Porphyria cutanea tarda
	Turner syndrome
	Urea cycle disorders
	Wilson’s disease

LAL: Lysosomal acid lypase.