1. NAFLD is in 3 stages
a) NAFL – just fat with ballooning but no damage
b) NASH is fat plus inflammation and scarring
2. US detects 50% NAFLD.
3. It is adipocyte dysfunction :
4. Secondary fat occurs in alcohol consumption, HCV type 3, lipodystrophy, starvation, TPN, abetalipoproteinemia, medications like amiodarone, methotrexate, tamoxifen, steroids. Microvascular steatosis occurs in Reyes syndrome etc
5. Most patients with NASH die from high CV disease.
6. Higher HCC in NASH and HCV and incidence increasing by 8% for HCV from 2004 to 2009 and 5% in NASH from same time frame
7. Measure fibrosis with fibrosure, Fibrospect 2, ELF, hepascore. Non patented are APRI, or Fib-4
8. Fibroscan, MRE,
9. NASH – tier 1 or tier 2. Use liver biopsy for high score on tier 1, eg more than 9.6kPA (M probe) or 9.3 on XL probe
10. NASH goal lose 5-10% of weight. Decrease carbohydrate and fructose. Caloric decrease by 25%. Use PUFA and not transfat. Fructose is high in soda, fast food, fruits, vegetables and dried fruits. Low fructose in strawberries, bananas, cantaloupe, pineapple, peaches, grapefruit, limes, avocados, tomatoes, apricots, mangos and plums
11. High transfat in meants, cream cheese, butter, ice cream, shortening, stick margarine.
12. High PUFA, nuts, seeds, avocados, olives,
13. Treatment with pioglitazone ( actos 30 mg/day), vitamin E. Study was PIVENS. No change in fibrosis. Risk of pioglitazone – use in biopsy proven NASH. Vitamin E increases all cause mortality and prostate cancer. Not recommended to use vitamin E in diabetic pt, without liver biopsy, NASH cirrhosis or cryptogenic cirrhosis
14. Future candidates are Victoza,
15. FLINT trial obeticholic acid. It is semisynthetic bile acid analogue and activator of farnesoid x nuclear receptor. It improved histology by 45%. Side effect is itching. Also resolved fibrosis completely in 15% !!!
16. LEAN study for victoza (liraglutide). Resolution of NASH in 39%.
17. Remogliflozin : ?
18. Target metabolic syndrome – DM , increased chol and TG. Metformin not effective, Statins are safe but no benefits.
19. Alcohol in NASH – neutral. Acceptable alcohol is 21 drinks in men and 14 drinks in women per week. Heavy drinking is 4 drinks per day for men and 3 drinks /day in women. (per NIAAA – national institute of alcohol abuse and )
20. 1 drink is 341 ml of 5% beer, etc
21. Liver tonics or cleansers – hydroxycut, black cohosh, or herbalife are harmful.
IV. FIBROSCAN AND OTHERS
1. Early cirrhosis from HBV can be reversed with viread
2. F1 fibrosis, F2 with septa and F4 cirrhosis.
3. — — USE APRI – AST to platelets ratio.
4. Sensitivity of Fibrosure is 60-75% and specific is 80-90%. Hepascore is the same (for F2). APRI is 77% sensitive and 72% specific. European liver fibrosis – F2 87% and specific is 40%. SHASTA for HIV. F 22 is 88% sensitive and specific 94%
5. APRI score 1-1.5 78% specific and 2 or more is 87% specific. If 0.5 84% sensitive. Same is true for NASH and HCV patients if you use APRI
6. Shear wave elastography ( transient or AFRI elastography) or strain elastography. Both are with US. Each one of them are 2 different types. One is semi quantitative and other is quantitative. Not a good test in heart failure, and affected by type of liver disease.
7. Shear wave – reported as kPa. Transient F2, F4 (78 and 89%). AFRI F2 and F4 (74 and 87%) sensitivity. And specificity for each is 84 and 87% and 83 and 87%. Both are equivalent modalities
8. The results are affected by inflammation and it increases the kPa. Like biomarkers are not reliable
9. Strain elastography – limited experience
10. MR elastography – better than US. F3 is 6.95 kPa
11. Algorithm – if APRI is more than 2, fibrotest more than 0.7 and TE more than 14 has cirrhosis and no bx needed. (if all 3 present)
12. If APRI less than 0.5, TE less than 7 kPa and fibrotest less than 0.2 – no biopsy…No cirrhosis. (if all 3 present).
13. Do biopsy if uncertain scores for above
14. The advantage is you can do TE every year on the same pt to measure progression
B. APRI score :
1. Divide the AST by 35.
2. Divide that number by the PLATELET count (this should be in the range 0 to 500 or so – if there are extra zeros, delete these before computing).
3. Multiply this number by 100.
4. If this number is greater than 0.5, there is a good chance they have some liver damage. If greater than 1.5, the person very likely has cirrhosis. One can say APRI scores between 0.5 to 1.5 VERY LOOSELY correspond to Metavir Stages 1-3, and above 1.5 corresponds (again, very loosely) to Metavir Stage 4.