Week 5: NAFLD and NASH

Question 1

Natural history of NAFLD

Answer 1

• 20-30% US have steatosis. 10-20% of those develop steatoheaptitis
• 10-20% those develop cirrhosis
• then can lead to HCC
• Cardiovascular disease is most common cause of death in NAFLD, though patients with NASH at higher risk of dying from liver disease

Question 2

Risk factors for NAFLD and NASH

Answer 2

Higher risk for developing NASH
-Obesity
-Type 2 DM
-dyslipidemia
-metabolic 
IF have NAFLD, risk factors for mortality are increased for: DM, age, cirrhosis.
-NASH higher in hispanic and african

Question 3

Pathogenesis for NAFLD and NASH

Answer 3

NAFLD
1. increased fatty intake
2. Increased de novo lipogenesis
3. Fat trapped in liver, TG can't leave.
NASH
-ROS, Fe, genetic, micro biome, stress,  may play role. Second "hit"

Question 4

Clinical presentation for NAFLD, NASH

Answer 4

Most are asymptomatic

• malaise, fatigue, RUQ discomfort
• PE: abdominal obesity, enlarged liver, RUQ tenderness on palpation
• Labs: consistent with metabolic syndrome, elevated bilirubin, AST, ALT, AP, GGT
• liver biochemistries can be normal.
• Biopsy is the only way to distinguish between NASH and non alcoholic fatty liver

Question 5

Indications for liver biopsy

Answer 5

• high ferritin (hemochromatosis)
• positive autoantibodies
• use of medications associated with drug induced liver disease
• staging of disease: several risk factors, e.g. metabolic syndrome
• biomarkers: cytokeratin 18

Question 6

Treatment for NASH/ NAFLD

Answer 6

1. Lifestyle interventions
   -weight loss
   -decreased EtOH
2. Insulin sensitizing agents
   -Metformin: no histological improvement
   -thiazolidinediones: improved steatosis, ballooning and inflammation but not fibrosis
3. Statins
4. Bariatric surgery
   AASLD GUIDELINES
   -pioglitazone: in biopsy proven NASH
   -Vitamin E improves liver histology in NASH patients. But not recommended if have DM, cirrhosis. But controversial.