Fatty Liver Disease

Question 0

Cut-off for daily alcoholic intake that constitute “high risk” for alcoholic liver disease?

Answer 0

6-8 drinks a day for men.

3-4 drinks a day for women.

Question 1

3 causes of fatty liver disease?

Answer 1

Alcoholic
Non-alcoholic
Other

Question 2

What does each step in normal (i.e. non-MEOS) alcohol metabolism produce?

Answer 2

NADH

Question 3

What does MEOS metabolism of alcohol produce?

Answer 3

Oxygen free radicals

Question 4

What effects does NADH have on the liver?

Answer 4

Promotes synthesis of fatty acids.
Decreases breakdown of fatty acids.
(leads to TG buildup in liver)

Question 5

How does fat in the liver cause a problem?

Answer 5

When the free radicals produced by MEOS attack fat -> lipid peroxidation -> Kupffer cell activation -> cytokines -> hepatitis/cirrhosis.

Question 6

What cytokines are involved in promoting hepatitis and cirrhosis?

Answer 6

TNF
TGF-beta
(and superoxide… not really a cytokine)

Question 7

What activates stellate cells to start laying down collagen, causing fibrosis?

Answer 7

Acetaldehyde
Oxygen free radicals
Lipid peroxidation products
TGF-beta

Question 8

Of steatosis, hepatitis, and cirrhosis, which is/are reversible?

Answer 8

Steatosis is reversible, as is hepatitis (if you don’t die).

Cirrhosis is not reversible.

Question 9

Can you go from steatosis to cirrhosis without having hepatitis first?

Answer 9

Yeah.

Question 10

Symptoms of steatosis?

Biochemistry changes?

Answer 10

Symptoms are mild and non-specific.

Biochemistry: mild elevation of AST and ALT.

Question 11

What percentage of people with alcoholic fatty liver go on to hepatitis/cirrhosis if they keep drinking?

Answer 11

20-30%

Question 12

What’s the AST:ALT ratio to remember in alcoholic hepatitis?

Answer 12

2:1

apparently this is very important

Question 13

What’s elevated, other than LFTs, in severe alcoholic hepatitis?

Answer 13

Prothrombin time

Bilirubin

Question 14

5 things you can detect on physical exam of alcoholic hepatitis?

Answer 14

Jaundice
Splenomegaly
Palmar erythema
Asterixis
Ascites

Question 15

What variables are most important in a patient surviving an acute episode of alcoholic hepatitis?

Answer 15

Prothrombin time

Bilirubin levels

Question 16

Treatment for severe alcoholic hepatitis?

Answer 16

Stop EtOH (obviously).
Steroids and/or pentoxifylline (maybe works by inhibiting TNF?).
Nutrition.
Monitor for and treat infections.

Question 17

Which has higher risk of being acutely fatal: hepatitis or cirrhosis?

Answer 17

Hepatitis - 60% 5-year survival if EtOH stopped, less than 30% if not.
Compensated alcoholic cirrhosis has 80% survival at 5 years if EtOH stopped.

Question 18

Cure for cirrhosis?

Answer 18

Transplant

Question 19

3 steps on the Non-Alcoholic Fatty Liver Disease (NAFLD) spectrum?

Answer 19

Steatosis
NASH (non-alcoholic steatohepatitis)
Cirrhosis

Question 20

What’s the approximate prevalence of NAFLD in the US?

Answer 20

20-30%

Question 21

2 factors that may contribute to progression to NASH from steatosis?

Answer 21

Insulin resistance

Oxidative stress on hepatocytes

Question 22

What are 2 ways in which insulin resistance is thought to contribute to progression to NASH?

Answer 22

Increased lipolysis: FFAs released from adipocytes and accumulate in liver (also, lipid peroxidation).
Hyperinsulinemia: (assuming liver not as insulin resistant as periphery) -> increased FFA synth in liver, decreased VLDL production.

Question 23

Based on retrospective studies, how many people with NASH go on to liver failure?

Answer 23

3%

Question 24

Drug therapy for NAFLD?

Answer 24

Insulin sensitizing agents - Rosiglatizone/Pioglitazone (people don’t use pioglitazone…)
Metformin
Antioxidants - Vit E, C, Betaine