Fatty Liver Disease Flashcards
What are risk factors for alcoholic liver disease? (4)
Alcohol (6-8 drinks/day for men; 3-4 for women)
Predisposing factors for alcoholism
Diet/nutrition
HepB/C
Describe how alcohol leads to fatty liver
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
What are mechanisms of alcohol-caused liver damage? (3)
Oxidative stress
Lipid peroxidation
Kipper cell activation==>Cytokine production
How does alcohol cause fibrosis?
Activation of stellate cells via: Acetaldehyde O2 radicals Products of lipid peroxidation TGF-ß
Describe presentation of fatty liver: symptoms, lab values, histology
Asymptomatic or mild vague symptoms (fatigue, malaise, anorexia, abd discomfort)
Mild to moderate elevated AST/ALT
Histology: macrovesicular steatosis
Describe outcomes of fatty liver
Entirely reversible if you discontinue EtOH
If continue to drink heavily, 20-30% progress to alcoholic hepatitis/cirrhosis
What are clinical symptoms of alcoholic hepatitis?
Occurs after years of heavy drinking
Weakness, anorexia, weight loss, nausea, vomiting
Severe: portal hypertension (varices, ascites, HE)
Describe the physical exam (5) and lab findings (3) of alcoholic hepatitis
Physical exam: jaundice, splenomegaly, palmar arrhythmia, asterixis, ascites
Lab: Elevated AST/ALT (AST more), increased prothrombin time, increased bilirubin
Describe histological findings of alcoholic hepatitis (5)
Macrovesicular steatosis PMN infiltrate Centrilobular hepatocyte swelling Ballooning degeneration Mallory bodies
What is the Maddrey Discriminant Function?
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
What are management options for alcoholic hepatitis? (4)
Stop EtOH
Severe disease: steroids/pentoxifylline
Nutrition
Treatment for infection
What is the treatment for alcoholic cirrhosis? (3) How does it affect prognosis?
Stop EtOH, manage complications of cirrhosis, OLT
If abstain, prognosis good (>50% survival even for decompensated cirrhosis)
If continue to drink, worse prognosis (
What is the spectrum of disease that is encompassed by NAFLD?
Steatosis
NASH
Cirrhosis
Describe the prevalence of NAFLD: overall and among obese patients
Overall prevalence=20-30%
Obese patients: 57-74%
How is NAFLD defined?
Fat infiltration in liver exceeds 5-10% by weight
What are risk factors for NAFLD? (4)
Obesity
Hyperglycemia
T2DM
Hypertriglyceridemia
What is metabolic syndrome? How is it defined?
3 of 5 criteria: Abdominal obesity Elevated triglycerides Low HDL cholesterol Elevated BP Elevated fasting plasma glucose
What two factors are involved in the hypothesis for development of steatohepatitis from steatosis?
Insulin resistance==> increased lipolysis, hyperinsulinemia==>increased storage of fat in liver
oxidative stress on hepatocytes
Describe the key difference in NASH vs. alcoholic liver disease
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
What is treatment for NAFLD? (4)
Weight reduction
Correction of central obesity
Insulin-sensitizing agents/antioxidants?
Manage complications of cirrhosis/transplant for advanced disease
What are other causes of fatty liver disease? (6)
Disorders of lipid metabolism TPN Wilson's disease Severe weight loss (i.e gastric bypass) Medications: steroids, HAART Toxic exposure
