Fatty Liver Disease

Question 0

How much alcohol consumption poses a risk factor for liver disease?

Answer 0

Male: 6-8 drinks
Female: 3-4 drinks

Question 1

What are the 2 main causes of liver failure and death in the US?

Answer 1

(1) alcoholic liver disease

(2) hepatitis C

Question 2

Describe normal alcohol metabolism.

Answer 2

(1) ADH converts alcohol to acetaldehyde.
(2) ALDH converts acetaldehyde to acetate.

Each step also converts NAD+ to NADH.

Question 3

J: Deficiency of this enzyme causes flushing syndrome after the consumption of alcohol.

Answer 3

What is ALDH?

Question 4

Describe alcohol metabolism when blood alcohol is high.

Answer 4

(1) MEOS converts alcohol to acetaldehyde.
(2) aldehyde or xanthine oxidase converts acetaldehyde to acetate.

Each step consumes NADPH and produces an oxyradical.

Question 5

How does alcohol lead to a fatty liver?

Answer 5

(1) Increased NADH.
(2) Increased fatty acid synthesis and decreased mitochondrial beta-oxidation of fatty acids.
(3) Fatty acids accumulate in hepatocytes and are esterified and stored as triglycerides.

Question 6

How does alcohol cause liver damage?

Answer 6

(1) Alcohol metabolism leads to oxidative stress and lipid peroxidation.
(2) Kupffer cell are activated, leading to cytokine and superoxide production.

Question 7

How does alcohol cause fibrosis?

Answer 7

Stellate cells, the primary collagen-producing cells in the liver, are activated by:

(1) acetaldehyde
(2) oxyradicals
(3) products of lipid peroxidation
(4) TGF-beta

Question 8

What are the primary collagen-producing cells in the liver?

Answer 8

Stellate cells.

Question 9

What is the clinical presentation of a fatty liver?

Answer 9

(1) no to mild symptoms: fatigue, malaise, anorexia, abdominal discomfort
(2) tender hepatomegaly
(3) mild AST/ALT increase

Question 10

Is fatty liver reversible?

Answer 10

Yes, just stop drinking.

Question 11

What is the clinical presentation of alcoholic hepatitis?

Answer 11

(1) constitutional symptoms
(2) esophageal varices
(3) ascites
(4) hepatic encephalopathy
(5) jaundice
(6) splenomegaly
(7) palmar erythema
(8) asterixis

Question 12

What is the LFT profile of alcoholic hepatitis?

Answer 12

AST:ALT is 2:1.

Question 13

What are the histological features of alcoholic hepatitis?

Answer 13

(1) macrovesicular steatosis
(2) acute inflammation
(3) centrilobular hepatocyte swelling
(4) ballooning degeneration
(5) Mallory bodies

Question 14

J: This is used to determine the risk of death in a patient with acute hepatitis.

Answer 14

What is the Maddrey discriminant function?

Question 15

How is alcoholic hepatitis treated?

Answer 15

(1) no alcohol

(2) adequate nutrition

Question 16

What is NAFLD?

Answer 16

Non-alcoholic fatty liver disease. It appears histologically like alcohol-induced disease but in a non-drinker or little-drinker.

Question 17

What is an unwanted progression of NAFLD?

Answer 17

(1) NAFLD
(2) NASH
(3) cirrhosis
(4) death

Question 18

What are risk factors for NAFLD?

Answer 18

(1) obesity
(2) hyperglycemia
(3) T2DM
(4) hypertriglyceridemia

Question 19

What is another name for metabolic syndrome?

Answer 19

Insulin resistance syndrome.

Question 20

What are the 2 main mechanisms by which insulin resistance leads to fat accumulation I the liver?

Answer 20

(1) increased lipolysis

(2) hyperinsulinemia

Question 21

How does increased lipolysis lead to NAFLD?

Answer 21

(1) Increased FFAs leads to increased uptake by hepatocytes, mitochondrial beta-oxidation overload, and accumulation of FFAs within hepatocytes.
(2) FFAs induce cytochrome P450 enzymes, leading to production of oxyradicals and lipid peroxidation.

Question 22

How does hyperinsulinemia lead to NAFLD?

Answer 22

(1) Increases glycolysis leading to increased synthesis of FFAs.
(2) Decreases hepatic production of ApoB-100, leading to decreased assembly and secretion of VLDL.

Question 23

How is NAFLD treated?

Answer 23

(1) weight reduction
(2) insulin-sensitizing agents (pioglitazone, metformin)
(3) antioxidants

Question 24

What are causes of fatty liver disease other than alcohol and NAFLD?

Answer 24

(1) disorders of lipid metabolism
(2) total parenteral nutrition
(3) Wilson disease
(4) severe weight loss
(5) steroids
(6) HIV medications