Drug-Induced Liver Disease: Waters

Question 1

How do OCPs cause cholestasis?

What else does estrogen do to the liver that is bad?

Answer 1

Estrogen decreases membrane fluidity–> decr. Na/KATPase activity and bile salt transport.

Also, Budd-Chiari = hepatic vein thrombosis
Focal nodular hyperplasia
Peliosis hepatis- venous lakes
Hepatic adenomas
HCC- rare w/ current doses, but still assoc.

Question 2

What drug is responsible for the VAST majority of liver failure in the U.S., including non-drug causes?

Answer 2

Tylenol (Acetaminophen) accounts for 46% of acute liver failure according to a 1998-2007 study.

Question 3

DO NOT COMBINE EtOH with:

Why not?

Answer 3

Tylenol
v glutathione
^ CYP450 induction
^ toxic metabolites
As little as 2.5-4g may be toxic in alcoholics

Question 4

What is the antidote for tylenol + EtOH toxicity?

Answer 4

N-acetylcysteine, repletes glutathione.
Toxic product of acetaminophen metab. is conjugated to glutathione and rendered harmless.
**Stops FURTHER damage, not damage that has already been done. **
It does not matter how late the pt presents or what their acetaminophen levels are, give the antidote, their liver will thank you.

Question 5

Grossly, what will you see on a cut liver after Tylenol poisoning?
Histologically?

Answer 5

Nutmeg liver (congestion)
Histo: necrosis around central vein (zone 3)

Question 6

Describe the general histologic changes in drug induced liver damage.

Answer 6

Hepatitis, neutrophilic, lymphocytic, eosinophilic, granulomatous, or any combination of those.
Look out for balloon degeneration- swollen, hydropic hepatocytes.
Can have cholestasis, bile plugs.
Can have Mallory-Denk bodies