Fatty Liver Disease

Question 1

What are risk factors for alcoholic liver disease? (4)

Answer 1

Alcohol (6-8 drinks/day for men; 3-4 for women)
Predisposing factors for alcoholism
Diet/nutrition
HepB/C

Question 2

Describe how alcohol leads to fatty liver

Answer 2

Increase in NADH increases fatty acid synthesis and decreases B oxidation.
Accumulation of fatty acids in hepatocyte cytoplasm leads to esterification and storage as triglycerides==>fatty liver

Question 3

What are mechanisms of alcohol-caused liver damage? (3)

Answer 3

Oxidative stress
Lipid peroxidation
Kipper cell activation==>Cytokine production

Question 4

How does alcohol cause fibrosis?

Answer 4

Activation of stellate cells via: 
Acetaldehyde
O2 radicals
Products of lipid peroxidation  
TGF-ß

Question 5

Describe presentation of fatty liver: symptoms, lab values, histology

Answer 5

Asymptomatic or mild vague symptoms (fatigue, malaise, anorexia, abd discomfort)

Mild to moderate elevated AST/ALT
Histology: macrovesicular steatosis

Question 6

Describe outcomes of fatty liver

Answer 6

Entirely reversible if you discontinue EtOH

If continue to drink heavily, 20-30% progress to alcoholic hepatitis/cirrhosis

Question 7

What are clinical symptoms of alcoholic hepatitis?

Answer 7

Occurs after years of heavy drinking
Weakness, anorexia, weight loss, nausea, vomiting
Severe: portal hypertension (varices, ascites, HE)

Question 8

Describe the physical exam (5) and lab findings (3) of alcoholic hepatitis

Answer 8

Physical exam: jaundice, splenomegaly, palmar arrhythmia, asterixis, ascites

Lab: Elevated AST/ALT (AST more), increased prothrombin time, increased bilirubin

Question 9

Describe histological findings of alcoholic hepatitis (5)

Answer 9

Macrovesicular steatosis
PMN infiltrate
Centrilobular hepatocyte swelling
Ballooning degeneration
Mallory bodies

Question 10

What is the Maddrey Discriminant Function?

Answer 10

Measures risk of death in alcoholics:

MDF= 4.6 (PT time of patient- control PT time) + [BR]

Survival based on whether pt can stop EtOH

Question 11

What are management options for alcoholic hepatitis? (4)

Answer 11

Stop EtOH
Severe disease: steroids/pentoxifylline
Nutrition
Treatment for infection

Question 12

What is the treatment for alcoholic cirrhosis? (3) How does it affect prognosis?

Answer 12

Stop EtOH, manage complications of cirrhosis, OLT

If abstain, prognosis good (>50% survival even for decompensated cirrhosis)

If continue to drink, worse prognosis (

Question 13

What is the spectrum of disease that is encompassed by NAFLD?

Answer 13

Steatosis
NASH
Cirrhosis

Question 14

Describe the prevalence of NAFLD: overall and among obese patients

Answer 14

Overall prevalence=20-30%

Obese patients: 57-74%

Question 15

How is NAFLD defined?

Answer 15

Fat infiltration in liver exceeds 5-10% by weight

Question 16

What are risk factors for NAFLD? (4)

Answer 16

Obesity
Hyperglycemia
T2DM
Hypertriglyceridemia

Question 17

What is metabolic syndrome? How is it defined?

Answer 17

3 of 5 criteria: 
Abdominal obesity
Elevated triglycerides
Low HDL cholesterol
Elevated BP
Elevated fasting plasma glucose

Question 18

What two factors are involved in the hypothesis for development of steatohepatitis from steatosis?

Answer 18

Insulin resistance==> increased lipolysis, hyperinsulinemia==>increased storage of fat in liver
oxidative stress on hepatocytes

Question 19

Describe the key difference in NASH vs. alcoholic liver disease

Answer 19

Alcoholic liver disease: more men, no DM/obesity, highly symptomatic, high AST

NASH: more common in women, associated with obesity/DM, rarely symptomatic and has normal AST:ALT ratio

Question 20

What is treatment for NAFLD? (4)

Answer 20

Weight reduction
Correction of central obesity
Insulin-sensitizing agents/antioxidants?
Manage complications of cirrhosis/transplant for advanced disease

Question 21

What are other causes of fatty liver disease? (6)

Answer 21

Disorders of lipid metabolism
TPN
Wilson's disease
Severe weight loss (i.e gastric bypass)
Medications: steroids, HAART
Toxic exposure