Week 4: alcoholic liver disease

Question 1

Risk factors for alcoholic liver disease

Answer 1

• male
• race and ethnicity: hispanics have higher risk
• presence of other liver diseases
• type of alcohol consumed
• binge drinking
• genetic polymorphisms of genes involved in alcohol metabolism
• duration of ~10 years
• amount of alcohol consumed, more than 30-40g/day in men and 20g/day in women (4-8 glasses of wine in men and 2-4 in women)
• Factors that accelerate pathogenesis: diabetes/obesity, Hep C, nutrition (high fat and Fe)

Question 2

Absorption, distribution, excretion of EtOH

Answer 2

• absorption of EtOh in stomach is slow, 50-80% absorbed in duodenum and upper jejunum
• poorly lipid soluble. an obese person attains a higher level of blood alcohol than a thin person
• brain, lungs, liver alcohol levels rapidly equilibrate with blood

Question 3

Pathogenesis of alcohol liver disease

Answer 3

Several possible mechanisms

1. variations in alcohol metabolism
   - can be metabolized by CYP2E1–>ROS production
2. centrilobular hypoxia
   - liver injury is most prominent around central vein. Furthest from oxygenated blood and highest concentration of CYP2E1
3. inflammatory cell infiltration and activation
   - chronic alcohol increases intestinal permeability, allows endotoxins into portal blood
   - exaggerates release of cytokines and oxygen radicals from alcohol primed Kupffer cells
   - leukocyte infiltration and activation
4. formation of oxygen radicals

Question 4

Clinical findings of alcoholic fatty liver

Answer 4

PE not sensitive or specific

• hepatomegaly due to fatty infiltration
• parotid gland enlargement
• Dupuytren’s contracture
• signs of feminization in men
• palmar erythema
• muscle wasting

Question 5

Labs in alcoholic liver disease

Answer 5

EARLY ALD
-liver panel may be normal 
-biomarkers for chronic alcohol abuse: carb deficient transferrin, urinary ethyl glucuroide
-bone marrow suppression
ADVANCED ALD
-abn. liver panel, high AST, ALT: never above 500 and AST: ALT at 2:1 ratio (ALT requires it B6, which is consumed in metabolizing alcohol)
-levels >300, think acetominophen
-high bilirubin
-decrease in protein and albumin
-increase in INR

Question 6

natural history of alcoholic liver disease

Answer 6

1. 90-95% of chronic alcohol abuses have steatosis (fatty liver)
2. 20-40% develop fibrosis
3. 8-20% then develop cirrhosis
   - alcoholic hepatitis is common in individuals who already have cirrhosis
4. 3-10% develop HCC

Question 7

Alcoholic fatty liver

Answer 7

• not specific to ALD
• hepatocytes contain macrovesicular droplets of triglycerides
• asymptomatic
• can be reversed with abstinence

Question 8

Alcoholic hepatitis

Answer 8

• subset of patients with ALD
• don’t necessarily need to have cirrhosis, but many already do
• many have stopped drinking recently due to being too sick
• findings: fever, jaundice, tender hepatomegaly, bruit over liver, portal HTN
• labs: AST/ALT 2:1, elevated wbc, abnormal INR, elevated total bili, elevated Cr (ominous is present)
• histology: cytologic ballooning, mallory bodies, PMNs

Question 9

Treatment of alcoholic hepatitis

Answer 9

• severity is measured by Maddrey score (bili and INR in equation). >32 is severe prognosis.
• initiate steroids for >32. Lille model says assess response of patients to steroids for 1 week. If able to reach certain levels based on labs, continue steroids, if not take off.
• Pentoxifylline: TNFa inhibitor
• nutrition assessment
• manage complications, e.g. portal HTN