Alcoholic Liver Disease (Waters/Nichols)

Question 1

MC chronic liver disease in the US?

Answer 1

hep C = 57%

alcoholic liver dz = 24%

Question 2

Complications of Alcoholic Liver Disease?

Answer 2

Steatosis
Alcoholic hepatitis 
Alcoholic cirrhosis
   →Hepatocellular carcinoma
   →Cholangiocarcinoma

Question 3

How much Etoh does it take to put you at an Alcoholic Liver Dz risk?

Answer 3

> 40-80 g/day (4-7 drinks) for greater than 5 yrs

*risk increases w/ amt Etoh

Question 4

How is Alcoholic Liver Disease in Men different from in women?

Answer 4

it appears sooner in F and with fewer drinks per day

due to differences in Etoh metabolism

Question 5

Epidemiology of Alcoholic Hepatitis?

Answer 5

40-60 years old

>80 gm Etoh/day for > 5 years
Often > 100 gm/day

Question 6

Clinical signs/symptoms of Alcoholic Hepatitis?

Answer 6

• Rapid onset of jaundice
• Fever
• Muscle wasting
• ascites
• Hepatomegaly with tenderness

Question 7

lab abn associated with alcoholic hepatitis?

Answer 7

• AST, ALT rarely over 300
• AST > 2x ALT
• Frequent leukocytosis
• Elevated INR

**(if >300, it’s something else + ETOH)

Question 8

How does risk of cirrhosis relate to high (>120g/day) Etoh consumption?

Answer 8

only 5.7% of people who drink that much actually get cirrhosis

**however, ~ 41% of alcoholics with hemachromatosis get cirrhosis

Question 9

Evidence for role of genetics in alcoholic cirrhosis?

Answer 9

• Concordance rate for alcoholic cirrhosis 3x times higher in monozygotic twins than dizygotic twins.
• possible susceptibility genes

Question 10

Mechanism if ETOH liver disease?

Answer 10

ETOH, Acetylaldehyde → intestinal injury + incr permeability → endotoxemia → cytokine response by Kupffer cells → damage to hepatocytes + apoptosis/necrosis

Question 11

Two Hit Theory of Etoh Liver Disease?

Answer 11

1st Hit → Fatty liver (fat = sensitive to insults)
- caused by oxidative stress, related to obesity/DM

2nd Hit → AFLD
- caused by inflmm, necrosis, oxidative stress, hypoxemia, immunological rxn

Question 12

Alcoholic Hepatitis, Predictors of Survival:

Answer 12

1. Maddrey Score
   (PT + bilirubin; 1 mo survival)
2. Glasgow Alcoholic Hepatitis Score
   (age, WBC, BUN, INR, bilirubin)
3. Model for End-Stage Liver Disease (MELD)
   (INR, bilirubin, Cr)

Question 13

Advanced liver disease in Alcoholics usually occurs in the presence of what other diseases?

Answer 13

Hepatitis C
Hemochromatosis
Alpha one antitrypsin deficiency

Question 14

What is ethanol abuse in Hemochromatosis (C282Y mutations) associated with?

Answer 14

• advanced fibrosis
• Increased cirrhosis
• shorter survival than those w/o etoh abuse

Question 15

Alcoholic cirrhotic patients with heterozygous C282Y mutations had:

Answer 15

• Increased hepatic iron scores

- Higher rates of hepatocellular carcinoma

Question 16

Most important environmental factors determining ALD risk (3)?

Answer 16

Ethanol patterns, obesity and associated hyperglycemia

Question 17

Treatment for ALD?

Answer 17

Abstinence

Optimize nutrition

Pentoxifylline (TNF α inhibitor)

Immunosuppression w/ CS (in select pts)

Question 18

The Spectrum of ALD, from most benign to most serious?

Answer 18

1. steatosis (reversible w d/c etoh)
2. Perivenular fibrosis
3. Alcoholic Hepatitis
4. Sub-Sinusoid fibrosis
5. cirrhosis +/- hepatocellular carcinoma

Question 19

In ALD, where is fibrosis first evident?

Answer 19

around central vein

Question 20

Only form of alcohol-induced liver disease that is predictable and probably dose mediated:

Answer 20

steatosis

present in ~90% of alcoholics

Question 21

Patients with perivenular fibrosis seem to be prone to develop:

Answer 21

more severe fibrosis (if they continue to abuse etoh)

Question 22

How is chronic viral hep different pathologically than alcoholic hep?

Answer 22

Chronic viral hepatitis = portal + periportal fibrosis

Etoh = Perivenular Fibrosis

Question 23

What cellular abn are seen in ALD?

Answer 23

• Megamitochondria
• balloon hepatocytes containing Mallory Bodies
• focal neutrophil and mononuclear infiltration

Question 24

What are mallory bodies?

Cells with Mallory Bodies are often found surrounded by:

Answer 24

eosinophilic aggregates of denatured cytoskeletal filaments in the cytoplasm of hepatocytes (often balloon hepatocytes)

polymorphonuclear neutrophils

Question 25

Sub-sinusoidal (or peri-cellular fibrosis) is fairly characteristic of alcohol and has considerable prognostic significance since:

Answer 25

it tends to progress to cirrhosis unless alcohol is discontinued.

Question 26

How is Alcoholic Cirrhosis characterized, pathologically?

Answer 26

• micronodular

- presence of small, homogenous-sized nodules and fine fibrous septa (scars)

Question 27

All patients with cirrhosis, regardless of etiology, have an increased incidence of:

Answer 27

HCC

“Patients with alcoholic cirrhosis have a 15x higher chances of developing HCC than the non-cirrhotic population.”