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
Anahbaghdad@gmail.com
8/30/2020NAFLD Prof. Dr. Saad S Al Ani 1
*Nonalcoholic Fatty
Liver Disease( NAFLD)
Clinical tips

2. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD Prof. Dr. Saad S Al Ani 6
*NAFLD
Could be :
*Fatty liver alone
or extreme:
*Nonalcoholic steatohepatitis
(NASH)

7. 8/30/2020NAFLD Prof. Dr. Saad S Al Ani 7
*Sequence of NAFLD
https://www.stockwinners.com/blog/tag/nonalcoholic-fatty-liver-disease-nafld/

8. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD Prof. Dr. Saad S Al Ani 10
*Nonalcoholic steatohepatitis
NASH (Cont.)
In 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD Prof. Dr. Saad S Al Ani 19
*Lyosomal acid lipase deficiency
(LAL-D)

20. 8/30/2020NAFLD 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. 8/30/2020NAFLD Prof. Dr. Saad S Al Ani 21
*Lyosomal acid lipase deficiency (LAL-D)
(cont.)
https://www.mdpi.com/1422-0067/18/6/1134

22. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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. 8/30/2020NAFLD 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 .