NAFLD Flashcards
What are the metabolic consequences of obesity leading to NAFLD?
Describe MASLD
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.
Long term health outcomes of NAFLD
- 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
Relationships between NAFLD and Lifestyle Factors: Diet
Epidemiology of NAFLD in pediatrics
- More prevalent in older adolescents
- Boys
- Asian & Hispanic
Common anthropometric and biochemical features in individuals with NAFLD
- 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.
What is acanthosis nigricans
Darkening of pigments of melanin
* cutaneous sign of insulin resistance
Does Meal Patterning Influence Risk for NAFLD?
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.
Clinical Diagnosis of NAFLD
- Overweight/ obese child with central obesity
- Mild elevations in serum ALT and AST
- Insulin resistance
- Acanthosis Nigricans (AN)
- Hyperlipidemia (about 2/3)
Dietary intake patterns in children
Carbohydrate Quality
* ↑ Glycemic Index (GI)
* ↑ Glycemic Load (GL)
Simple Sugar Intake
* ↑ Fructose & Sucrose Intake
Type of Fat
* ↑ Saturated Fat
* ↓ Polyunsaturated Fat (PUFA)
Practice guidelines for lifestyle treatment of NAFLD
- 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
Drug treatment for NAFLD
- 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
Surgery for NAFLD
bariatric surgery
* may be viable treatment option for adults with NAFLD
* unclear in childhood-no clear evidence
Problems with weight loss diets
Main problem: nutrient imbalance
Secondary problem: poor adherence because too complicated
What dietary constituent could be eliminated from diet without affecting overall nutrient distribution?
- SUCROSE (table sugar) / Fructose → reduce sugar sweetened beverages
- Quality of Fat
- Glycemic Index / Glycemic Load → choosing WG foods
- isocaloric diets versus low-energy
Exercise as a Treatment for NAFLD
- 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.
Treatment medications
- 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.
lifestyle modifications vs. medication treatment
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.
