NAFLD

Question 1

What are the metabolic consequences of obesity leading to NAFLD?

Answer 1

Question 2

Describe MASLD

Answer 2

Metabolic Dysfunction Associated Steatotic Liver Disease → Emerging consensus that NAFLD should be renamed to “MASLD”, particularly in adults.
* This change in definition would enable the inclusion of adults with Diabetes (> 30% of adults with T2D have a fatty liver).
* Some concern in Pediatric NAFLD where there is a large classification of metabolic liver diseases due to inborn errors of metabolism.
* The definition may be expanded to include a Met- ALD.
* Still in process.

Question 3

Long term health outcomes of NAFLD

Answer 3

• Increased risk for liver cirrhosis
• Increased risk for liver failure (one of the top two reasons for need for liver transplantation in adults in US and Canada (number 1 reason in ONT).
• Significant co-morbidity inpatients with viral hepatitis and influences long term prognostic outcome.
• In childhood long term outcomes are unclear

Question 4

Relationships between NAFLD and Lifestyle Factors: Diet

Answer 4

Question 5

Epidemiology of NAFLD in pediatrics

Answer 5

• More prevalent in older adolescents
• Boys
• Asian & Hispanic

Question 6

Common anthropometric and biochemical features in individuals with NAFLD

Answer 6

• Central obesity/ overweight/ obese
• Insulin resistance typically with normal glycemic control/ hyperinsulinemia (reduced clearance by liver)
• Acanthosis nigricans (darkening of skin)
• Dyslipidemia-hypertriglyceridemia ± hypercholesterolemia (↑LDL/ ↓HDL)
• Depressed adiponectin/ erythrocyte glutathione/ ↑markers of oxidative stress & inflammation.

Question 7

What is acanthosis nigricans

Answer 7

Darkening of pigments of melanin
* cutaneous sign of insulin resistance

Question 8

Does Meal Patterning Influence Risk for NAFLD?

Answer 8

Emerging evidence that trends in meal patterning might be influencing disease pathogenesis in NAFLD.
* High saturated fat might contribute to increased vulnerability to hepatic oxidative stress and inflammation.
* High simple sugar intake; fructose appears to be a major concern. Animal models indicate that denovo lipogenesis ↑ with ↑ fructose diets; human data equivocal.

Question 9

Clinical Diagnosis of NAFLD

Answer 9

• Overweight/ obese child with central obesity
• Mild elevations in serum ALT and AST
• Insulin resistance
• Acanthosis Nigricans (AN)
• Hyperlipidemia (about 2/3)

Question 10

Dietary intake patterns in children

Answer 10

Carbohydrate Quality
* ↑ Glycemic Index (GI)
* ↑ Glycemic Load (GL)

Simple Sugar Intake
* ↑ Fructose & Sucrose Intake

Type of Fat
* ↑ Saturated Fat
* ↓ Polyunsaturated Fat (PUFA)

Question 11

Practice guidelines for lifestyle treatment of NAFLD

Answer 11

• Weight loss generally reduces hepatic steatosis, achieved either by hypocaloric diet alone or in conjunction with increased physical activity. (Strength – 1, Evidence – A)
• Loss of at least 3-5% of body weight appears necessary to improve steatosis, but a greater weight loss (up to 10%) may be needed to improve necroinflammation. (Strength – 1, Evidence – B)
• Exercise alone in adults with NAFLD may reduce hepatic steatosis but its ability to improve other aspects of liver histology remains unknown. (Strength – 1, Evidence – B)

No information about what is the best way to achieve weight loss

Question 12

Drug treatment for NAFLD

Answer 12

• Insulin sensitizers (metformin)
• Antioxidants (vitamin E most efficacious)
• Others: Choloretics, Lipid lowering agents, Betaine, Orlistat (interferes with fat absorption), Angiotensin II receptor antagonist, Probiotics, CB1 Endocannabanoid antagonist

Question 13

Surgery for NAFLD

Answer 13

bariatric surgery
* may be viable treatment option for adults with NAFLD
* unclear in childhood-no clear evidence

Question 14

Problems with weight loss diets

Answer 14

Main problem: nutrient imbalance
Secondary problem: poor adherence because too complicated

Question 15

What dietary constituent could be eliminated from diet without affecting overall nutrient distribution?

Answer 15

• SUCROSE (table sugar) / Fructose → reduce sugar sweetened beverages
• Quality of Fat
• Glycemic Index / Glycemic Load → choosing WG foods
• isocaloric diets versus low-energy

Question 16

Exercise as a Treatment for NAFLD

Answer 16

• High impact aerobic exercise has an independent effect on reducing intrahepatic fat.
• Lower intensity exercise is less effective; but may depend on type of exercise (eg. resistance) and duration of exercise intervention.

Question 17

Treatment medications

Answer 17

• Metformin has no significant effects on liver histology and is not recommended as a specific treatment with NASH (Evidence A, Strength 1).
• Pioglitazone can be used to treat NASH (biopsy proven), but long term safety is not established (Evidence B)
• Statin should not be used specifically to treat NASH.
• Vitamin E (α-tocopherol) administered daily at 800 IU/D improves liver histology in non-diabetic adults (not more effective than weight loss). Not established efficacy in diabetic patients without liver BX.
• UCDA (URSO) and/or omega 3 FA not recommended though it could be used to treat hypertriglyceridemia.

Question 18

lifestyle modifications vs. medication treatment

Answer 18

Lifestyle modification is equally efficacious to anti- oxidant therapy/pharmaceutical therapy. More research is needed (RCT) design to assess efficacy of specific approaches; particularly related to histological improvements of disease.