Liver - Week 6

Question 1

What are risk factors for NAFLD/NASH?

Answer 1

*- Abdominal obesity
     > Waist circumference of > 102cm (40in) in men and > 88cm (34.5in) in women
*- Metabolic syndrome/pre-DM
     > HbA1c 5.7-6.4%
*- Diabetes (HbA1c > 6.5%)
     > Includes family history of DM2
- Insulin resistance
*- Hypertension
- Hyperlipidemia
- Hypothyroidism
- Sleep apnea
- High refined carb/high fat intake
- Excessive fructose consumption
     > Especially combined with low fiber diets
- Pharmaceuticals
- Surgical procedures
     > Bariatric surgery
- Female > male
- Increasing age (post-menopause)

Question 2

What are the key diagnostics for NAFLD/NASH?

Answer 2

Labs that increase risk
- ALT:AST ratio > 1
     > ALT over 33 for males, over 19 for females
- Triglycerides > 150
- HDL < 40
- Fasting glucose > 100
- HbA1c > 5.7%
- Fasting insulin < 25
- CRP elevation
- Vitamin D3 (amount?)
- Ferritin > 300 males and > 200 females
- BP > 130/85

Diagnostic procedures
- There are no diagnostic or imaging tests to positively diagnose NASH
*- Must do a liver biopsy to distinguish between NASH and non-NASH
> Best to be US-guided
- US is unreliable if steatosis is < 33% of liver volume
- FibroTest/ActiTest
> Usually for monitoring progression or therapeutic intervention
> Less invasive than bx
> Usually used with HCV/HBV

Question 3

Discuss the effects of fructose on the body.

Answer 3

• Almost complete hepatic metabolism
• Rapid hepatic conversion into glucose, glycogen, lactate, and fat
  > Converted to fat at a higher rate than glucose
• Chronic consumption may cause dyslipidemia and may impair hepatic insulin sensitivity
  > Worse effects in rodents
• Doesn’t stimulate insulin, so doesn’t curb appetite
• Can lead to SIBO

Question 4

Compare fructose metabolism and alcohol metabolism.

Answer 4

-

Question 5

What is the outcome of continual fructose consumption on uric acid levels?

Answer 5

• Uric acid will be increased
  > Due to ATP breakdown to peptides in an effort to maximize phosphate groups for fructose metabolism
  ^ Fructose metabolism requires phosphate groups

Question 6

Which pharmaceuticals are risk factors for NASH?

Answer 6

• Calcium channel blockers
• Tamoxifen
• Corticosteroids
• Synthetic estrogens
• Aspirin
• Methotrexate
• Valproic acid
• Cocaine
• AZT
• Amiodarone

Question 7

What is the basic treatment protocol for NASH?

Answer 7

• Promote weight loss
• Lipid, insulin, and glucose normalization

Diet
- High in good-quality protein
- Healthy fats (emphasize omega-3)
- High in fresh vegetables
> Reduced starchy vegetables
- Low carbohydrate intake (< 30g of net carbs/day)
> Gluten/grain-free is best
- Lowered glycemic index/load
- Green tea (decreases intrahepatic fat accumulation)
- Coffee without sweeteners (insulin sensitizer)
- Frequent smaller meals
- Strictly avoid alcohol, sugar, fructose, and soda

Exercise

• Daily exercise (aerobic and weight-bearing)
• Start with 30 minutes/day and work up to 60 minutes/day
• Work with ability to change sedentary habits

Supplements

• Multivitamin
• Vitamin E 800 IU/QD
• Fish oil 6-9g of total EFA/QD
• Chromium 500 mcg/QD
• Vitamin D3 (enough to maintain 60-90 ng/mL)
• N-acetyl cysteine 600-2400 mg/QD
• Alpha-lipoic acid 600 mg/QD
• Betaine
• B complex
• Zinc
• Magnesium
• Manganese
• Probiotics

Herbs
- Liver protectant and cholagogues
     > Silymarin
     > Licorice
     > Green tea extract
- Insulin sensitizing herbs
     > Gymnema
     > Momordica charantia (bitter melon)
     > Cinnamon
     > Cassia bark