Table Info

Table 1.

Some conditions which can present with fatty liver and/or hypertransaminasemia [1, 2, 4, 5, 17, 19]

Genetic and metabolic causes	Toxics and drugs	Nutritional/GI and hepatic causes
Urea cycle disorders	Ethanol	Celiac disease
Hereditary fructose intolerance/galactosemia/tyrosinemia	Ecstasy	Inflammatory bowel disease
Glycogenosis I and VI and IX	Nifedipine	Intestinal failure
Bile acids synthesis defects	Diltiazem	Dysbiosis
Citrin deficiency	Cocaine	Viral hepatitis (HCV and HBV)
Cystic fibrosis	Solvents	Autoimmune hepatitis
Schwachman-Diamond syndrome	Pesticides	Kwashiorkor/malnutrition
Wilson’s disease	Glucocorticoids	Anorexia nervosa
Lipid storage disease Niemann-Pick disease type C	Estrogens	Rapid weight loss
Abeta/hypobetalipoproteinemia	Sodium valproate	Parenteral nutrition
Mitochondrial, fatty acids° α- and β-oxidation defects*	Methotrexate	Obesity
ER function (e.g., CDG) or protein metabolism disorders	Amiodarone	PCOS
Alpha 1-AT deficiency	Tetracycline	OSAS
NBAS	L-asparaginase	Endocrine causes
Turner syndrome	Aspirin	Hypothyroidism
Lipodystrophies	Antipsychotics	Hypothalamic-pituitary disorders
Porphyria cutanea tarda	Antidepressants	Diabetes mellitus type 1 (Mauriac syndrome)
Familial hyperlipoproteinemia	Antiretroviral drugs	Sepsis
Porto-systemic shunt	Vitamin E	Others
Some myopathic disorders

MCADD, LCHAD, VLCHAD, MADD; ^*mitochondria and other organelle dysfunction leading to the accumulation of fat droplets, and peroxisomal defects, frequently microvacuolar; Alpha 1-AT: alpha 1-antitrypsin; CDG: congenital disorders of glycosylation; ER: endoplasmic reticulum; NBAS: neuroblastoma amplified sequence; OSAS: obstructive sleep apnea syndrome; PCOS: polycystic ovarian syndrome; MCADD: medium-chain acyl-CoA dehydrogenase deficiency; LCHAD: long-chain 3-hydroxyacyl-CoA dehydrogenase; VLCHAD: very long-chain 3-hydroxyacyl-CoA dehydrogenase; MADD: multiple acyl-CoA dehydrogenase deficiency

Supplementary materials

The supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/100151_sup_1.pdf.

Declarations

Author contributions

MCR, AC and PV contributed conception and design of the study and reviewed the literature; CM wrote the first draft of the manuscript; MCR, AC, AGEDA, LN, PV and CM wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Alfani R, Vassallo E, De Anseris AG, Nazzaro L, D’Acunzo I, Porfito C, et al. Pediatric fatty liver and obesity: not always just a matter of non-alcoholic fatty liver disease. Children (Basel). 2018;5:169. [DOI]

Hegarty R, Deheragoda M, Fitzpatrick E, Dhawan A. Paediatric fatty liver disease (PeFLD): all is not NAFLD - pathophysiological insights and approach to management. J Hepatol. 2018;68:1286–99. [DOI] [PubMed]

Franzese A, Vajro P, Argenziano A, Puzziello A, Iannucci MP, Saviano MC, et al. Liver involvement in obese children (ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population). Dig Dis Sci. 1997;42:1428–32. [DOI] [PubMed]

Vajro P, Lenta S, Socha P, Dhawan A, McKiernan P, Baumann U, et al. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2012;54:700–13. [DOI] [PubMed]

Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017;64:319–34. [DOI] [PubMed] [PMC]

Di Bonito P, Pacifico L, Licenziati MR, Maffeis C, Morandi A, Manco M, et al. Elevated blood pressure, cardiometabolic risk and target organ damage in youth with overweight and obesity. Nutr Metab Cardiovasc Dis. 2020;30:1840–7. [DOI] [PubMed]

Di Bonito P, Valerio G, Licenziati MR, Miraglia Del Giudice E, Baroni MG, Morandi A, et al. High uric acid, reduced glomerular filtration rate and non-alcoholic fatty liver in young people with obesity. J Endocrinol Invest. 2020;43:461–8. [DOI] [PubMed]

Di Sessa A, Guarino S, Umano GR, Arenella M, Alfiero S, Quaranta G, et al. MAFLD in obese children: a challenging definition. Children (Basel). 2021;8:247. [DOI] [PubMed] [PMC]

Delli Bovi AP, Marciano F, Mandato C, Siano MA, Savoia M, Vajro P. Oxidative stress in non-alcoholic fatty liver disease. An updated mini review. Front Med (Lausanne). 2021;8:595371. [DOI] [PubMed] [PMC]

10.

EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease.Obes Facts. 2016;9:65–90. [DOI] [PubMed] [PMC]

11.

Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328–57. [DOI] [PubMed]

12.

Lin YC, Wu CC, Ni YH. New perspectives on genetic prediction for pediatric metabolic associated fatty liver disease. Front Pediatr. 2020;8:603654. [DOI] [PubMed] [PMC]

13.

Eslam M, Sanyal AJ, George J; International Consensus Pane. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020;158:1999–2014.e1. [DOI] [PubMed]

14.

Flisiak-Jackiewicz M, Bobrus-Chociej A, Wasilewska N, Lebensztejn DM. From nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD)-new terminology in pediatric patients as a step in good scientific direction? J Clin Med. 2021;5:924. [DOI]

15.

Huang J, Kumar R, Wang M, Zhu Y, Lin S. MAFLD criteria overlooks a number of patients with severe steatosis: is it clinically relevant? J Hepatol. 2020;73:1265–7. [DOI] [PubMed]

16.

Hegarty R, Singh S, Bansal S, Fitzpatrick E, Dhawan A. NAFLD to MAFLD in adults but the saga continues in children: an opportunity to advocate change. J Hepatol. 2021;74:991–2. [DOI] [PubMed]

17.

Fitzpatrick E, Dhawan A. Childhood and adolescent nonalcoholic fatty liver disease: is it different from adults? J Clin Exp Hepatol. 2019;9:716–22. [DOI] [PubMed] [PMC]

18.

Hegarty R, Dhawan A. Abnormal liver enzymes in fat or lean children should always be a cautionary tale. J Pediatr Gastroenterol Nutr. 2019;68:e40. [DOI]

19.

Vajro P, Maddaluno S, Veropalumbo C. Persistent hypertransaminasemia in asymptomatic children: a stepwise approach. World J Gastroenterol. 2013;19:2740–51. [DOI] [PubMed] [PMC]

20.

Vajro P. Transaminases and pediatric nonalcoholic fatty liver disease diagnosis. J Pediatr Gastroenterol Nutr. 2017;65:e114. [DOI] [PubMed]

21.

Draijer LG, Feddouli S, Bohte AE, Vd Baan Slootweg O, Pels Rijcken TH, Benninga MA, et al. Comparison of diagnostic accuracy of screening tests ALT and ultrasound for pediatric non-alcoholic fatty liver disease. Eur J Pediatr. 2019;178:863–70. [DOI] [PubMed] [PMC]

22.

Draijer L, Benninga M, Koot B. Pediatric NAFLD: an overview and recent developments in diagnostics and treatment. Expert Rev Gastroenterol Hepatol. 2019;13:447–61. [DOI] [PubMed]

23.

Mosca A, Panera N, Crudele A, Alisi A. Noninvasive diagnostic tools for pediatric NAFLD: where are we now? Expert Rev Gastroenterol Hepatol. 2020;14:1035–46. [DOI] [PubMed]

24.

Dezsőfi A, Baumann U, Dhawan A, Durmaz O, Fischler B, Hadzic N, et al. Liver biopsy in children: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2015:60:408–20. [DOI] [PubMed]

25.

Mann J, Reeves HL, Feldstein AE. Liquid biopsy for liver diseases. Gut. 2018;67:2204–12. [DOI] [PubMed]

26.

Riley MR, Bass NM, Rosenthal P, Merriman RB. Underdiagnosis of pediatric obesity and underscreening for fatty liver disease and metabolic syndrome by pediatricians and pediatric subspecialists. J Pediatr. 2005;147:839–42. [DOI] [PubMed]

27.

Zimmet P, Alberti G, Kaufman F, Tajima N, Silink M, Arslanian S, et al. The metabolic syndrome in children and adolescents. The Lancet. 2007;369:2059–61. [DOI]

28.

Goodman E, Daniels SR, Meigs JB, Dolan LM. Instability in the diagnosis of metabolic syndrome in adolescents. Circulation. 2007;115:2316–22. [DOI] [PubMed] [PMC]

29.

Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988–1994. Arch Pediatr Adolesc Med. 2003;157:821–7. [DOI] [PubMed]

30.

Ahrens W, Moreno LA, Mårild S, Molnár D, Siani A, De Henauw S, et al. Metabolic syndrome in young children: definitions and results of the IDEFICS study. Int J Obes (Lond). 2014;38 Suppl 2:S4–14. [DOI] [PubMed]

31.

Troisi J, Belmonte F, Bisogno A, Lausi O, Marciano F, Cavallo P, et al. Salivary markers of hepato-metabolic comorbidities in pediatric obesity. Dig Liver Dis. 2019;51:516–23. [DOI] [PubMed]

32.

Troisi J, Belmonte F, Bisogno A, Pierri L, Colucci A, Scala G, et al. Metabolomic salivary signature of pediatric obesity related liver disease and metabolic syndrome. Nutrients. 2019;11:274. [DOI]

33.

Yıldız Y, Sivri HS. Inborn errors of metabolism in the differential diagnosis of fatty liver disease. Turk J Gastroenterol. 2020;31:3–16. [DOI] [PubMed] [PMC]