Nonalcoholic fatty liver disease NAFLD in children

What is nonalcoholic fatty liver disease, what is the prevalence among children ,the definition of NAFLD,What are the relationship between obesity and over weight with the development of NAFLD,what are the sequences ,what is NASH,Who are at risk , How to diagnosis NAFLD what is the differential diagnosis ,what is the treatment

1. Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Saad’s Kids Clinic [email protected] 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 1 Nonalcoholic Fatty Liver Disease( NAFLD) Clinical tips

2. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 2 Introduction Childhood obesity can adversely affect nearly every organ system with increased mortality in adult life from a wide variety of systemic diseases Nobili V, Alisi A, Newton KP, Schwimmer JB. Comparison of the Phenotype and Approach to Pediatric vs Adult Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2016;150:1798–1810

3. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 3 Introduction (Cont.) The worldwide prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with potential serious health implications following the current epidemic of obesity . Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766–781.

4. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 4 Introduction (Cont.) There is a widespread tendency to draw alarming scenarios also for childhood NAFLD (1) (1)Pediatric Nonalcoholic Fatty Liver Disease: the Rise of a Lethal Disease Among Mexican American Hispanic Children. Betancourt -Garcia MM, Arguelles A, Montes J, Hernandez A, Singh M, Forse RA Obes Surg. 2017 Jan; 27(1):236-244 . http:// pediatric-house-calls.djmed.net/wp-content/uploads/2013/09/graphic-fatty-liver.jpg

5. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 5 Nonalcoholic Fatty Liver Disease ( NAFLD) A spectrum of liver diseases strongly associated with obesity , is the most common chronic liver disease in children Della Corte C, Mazzotta AR, Nobili V. Fatty liver disease and obesity in youth. Curr Open Endocrinol Obes . 2016;23(1):66–71

6. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 6 NAFLD Could be : Fatty liver alone or extreme: Nonalcoholic steatohepatitis ( NASH )

7. 8/31/2020 NAFLD Prof. Dr. Saad S Al Ani 7 Sequence of NAFLD https://www.stockwinners.com/blog/tag/nonalcoholic-fatty-liver-disease-nafld /

8. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 8 Nonalcoholic steatohepatitis ( NASH ) A triad of : 1. Fatty infiltration 2. Inflammation 3. Fibrosis Yan Y, Hou D, Zhao X, et al. Childhood adiposity and nonalcoholic fatty liver disease in adulthood. Pediatrics . 2017;139(4):e20162738 .

9. 8/31/2020 NAFLD Prof. Dr. Saad S Al Ani 9 NASH NASH  is the severe form of Non-Alcoholic Fatty Liver Disease (NAFLD). It can lead to liver cancer, cirrhosis, and liver transplants.

10. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 10 Nonalcoholic steatohepatitis ( NASH ) (Cont.) I n children ,it has 2 distinct histologic types: 1. Type 1 NASH * Resembles adult histologic findings - steatosis and balloon degeneration of hepatocytes and/or peripheral fibrosis Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med . 2017;377(21):2063–2072 .

11. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 11 Nonalcoholic steatohepatitis ( NASH ) (Cont.) 2. Type 2 NASH - steatosis and portal inflammation Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med . 2017;377(21):2063–2072 .

12. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 12 ! Many patients with NAFLD are asymptomatic 38% of obese children aged 2-19 yr. old have NAFLD on autopsy Schwimmer JB. Clinical advances in pediatric nonalcoholic fatty liver disease. Hepatology . 2016;63(5):1718–1725

13. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 13 ! A normal serum aminotransferase (ALT) level is present in 21-23% of pediatric patients with NAFLD Elevated ALT levels are not sensitive or specific markers for NAFLD Schwimmer JB. Clinical advances in pediatric nonalcoholic fatty liver disease. Hepatology . 2016;63(5):1718–1725

14. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 14 ! (cont.) Ultrasound detects NAFLD but liver biopsy may be required for a delimiting diagnosis Schwimmer JB. Clinical advances in pediatric nonalcoholic fatty liver disease. Hepatology . 2016;63(5):1718–1725

15. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 15 Risk factors Obesity Male gender White or Hispanic ethnicity Hypertriglyceridemia Insulin resistance Yan Y, Hou D, Zhao X, et al. Childhood adiposity and nonalcoholic fatty liver disease in adulthood. Pediatrics . 2017;139(4):e20162738 .

16. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 16 ? Children with NAFLD should be screened for comorbid conditions , including: * diabetes * hypertension * dyslipidemia * obstructive sleep apnea Carbone LJ, Angus PW, Yeomans ND. Incretin-based therapies for the treatment of non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Gastroenterol Hepatol . 2016;31(1):23–31 [PMID] 26111358

17. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 17 ! Obese and overweight children with other risk factors >3 yr. of age should be screened for NAFLD by: - Checking ALT level - Liver ultrasound even though neither is highly sensitive or specific Della Corte C, Mazzotta AR, Nobili V. Fatty liver disease and obesity in youth. Curr Open Endocrinol Obes . 2016;23(1):66–71

18. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 18 Histopathological DD Lyosomal acid lipase deficiency ( LAL-D ) Autosomal recessive disorder Mutation in LIPA . Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med . 2017;377(21):2063–2072

19. 8/31/2020 NAFLD Prof. Dr. Saad S Al Ani 19 Lyosomal acid lipase deficiency (LAL-D)

20. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 20 Lyosomal acid lipase deficiency ( LAL-D ) (cont.) Hepatic steatosis -like syndrome Microvesicular or mixed micro- and macrovesicular steatosis NOT macrovesicular changes. Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med . 2017;377(21):2063–2072

21. 8/31/2020 NAFLD Prof. Dr. Saad S Al Ani 21 Lyosomal acid lipase deficiency ( LAL-D ) (cont.) https:// www.mdpi.com/1422-0067/18/6/1134

22. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 22 Treatment No definitive treatment for NAFLD Gradual weight loss is effective Low glycemic index foods and substitution of polyunsaturated fatty acids for saturated fats

23. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 23 Treatment (cont.) The most effective treatment for patients with NAFLD, both adults and children, is lifestyle optimization , with a focus on nutrition and exercise .

24. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 24 Treatment (cont.) Modulating gut microbiota with: probiotics , prebiotics, and synbiotics has become an attractive, safe and well tolerated treatment strategy of obesity and NAFLD. Nobili V, Cucchiara S. The Use of Probiotics in Pediatric Nonalcoholic Fatty Liver Disease: Teachable Moment or Missed Opportunity? J Pediatr Gastroenterol Nutr . 2017;64:336–337

25. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 25 Treatment (cont.) Unfortunately, the majority of obese children are not adherent to lifestyle modifications and hypocaloric diets Kovács E, Siani A, Konstabel K, Hadjigeorgiou C, de Bourdeaudhuij I, Eiben G, Lissner L, Gwozdz W, Reisch L, Pala V, et al. Adherence to the obesity-related lifestyle intervention targets in the IDEFICS study. Int J Obes (Lond) 2014;38 Suppl 2:S144–S151

26. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 26 Treatment (Cont.) Vitamin E improve balloon degeneration in children with NASH Usage of ɯ-3 docosahexaenoeic acid improve: * Insulin sensitivity * ALT * Triglycerides * BMI * Histology in children with NAFLD

27. 8/30/2020 NAFLD Prof. Dr. Saad S Al Ani 27 Treatment (Cont.) Usage of Cysteamine bitartrate (precursor of glutathione) (Antioxidant) reduce: * Liver enzyme levels * Serum leptin and adiponectin levels

28. 8/31/2020 NAFLD Prof. Dr. Saad S Al Ani 28 References Nobili V, Alisi A, Newton KP, Schwimmer JB. Comparison of the Phenotype and Approach to Pediatric vs Adult Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2016;150:1798–1810 Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766–781. Pediatric Nonalcoholic Fatty Liver Disease: the Rise of a Lethal Disease Among Mexican American Hispanic Children.Betancourt -Garcia MM, Arguelles A, Montes J, Hernandez A, Singh M, Forse RA http:// pediatric-house-calls.djmed.net/wp-content/uploads/2013/09/graphic-fatty-liver.jpg Della Corte C, Mazzotta AR, Nobili V. Fatty liver disease and obesity in youth. Curr Open Endocrinol Obes . 2016;23(1):66–71 Yan Y, Hou D, Zhao X, et al. Childhood adiposity and nonalcoholic fatty liver disease in adulthood. Pediatrics . 2017;139(4):e20162738 Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med . 2017;377(21): 2063–2072 Schwimmer JB. Clinical advances in pediatric nonalcoholic fatty liver disease. Hepatology . 2016;63(5): 1718–1725

29. 8/31/2020 NAFLD Prof. Dr. Saad S Al Ani 29 References (Cont.) Carbone LJ, Angus PW, Yeomans ND. Incretin-based therapies for the treatment of non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Gastroenterol Hepatol . 2016;31(1):23–31 [PMID] 26111358 Nobili V, Cucchiara S. The Use of Probiotics in Pediatric Nonalcoholic Fatty Liver Disease: Teachable Moment or Missed Opportunity? J Pediatr Gastroenterol Nutr . 2017;64:336–337 Kovács E, Siani A, Konstabel K, Hadjigeorgiou C, de Bourdeaudhuij I, Eiben G, Lissner L, Gwozdz W, Reisch L, Pala V, et al. Adherence to the obesity-related lifestyle intervention targets in the IDEFICS study. Int J Obes (Lond) 2014;38 Suppl 2:S144–S151 Obes Surg. 2017 Jan; 27(1):236-244Della Corte C, Mazzotta AR, Nobili V . Fatty liver disease and obesity in youth. curr Open Endocrinol Obes.2016;23(1):66-71 Himes RW, Barlow SE, Bove K ,et al. Lysosomal acid lipase deficiency unmasked in two children with nonalcoholic fatty liver disease. Pediatrics. 2016;138(4):e20160214 Kohli R ,Sunduram S , Mouzaki M , et al . Pediatric nonalcoholic fatty liver disease: a report from the expert committee on nonalcoholic fatty liver disease (ECON). J Pediatr. 2016;172:9-13 Yan Y ,Hou D ,Zhao X ,et al. Childhood adiposity and nonalcoholic fatty liver disease in adulthood . Pediatrics. 2017;139(4): e20162738 Abdou RM, Zhu L, Baker RD, et al. Gut Microbiota of nonalcoholic fatty liver disease. Dig Dis Sci . 2016;61(5):1268–1281 .