Lecture 21: Alcoholic and Nonalcoholic Fatty Liver

Question 1

How does someone wth ALD improve the state of their liver?

Answer 1

Abstinence

Question 2

ALD: Gender differences

Answer 2

Gastric mucosal ADH lower in women –> greater hepatic exposure to alcohol

Question 3

ALD: HCV/HBV interaction

Answer 3

Viral hepatitis worsens ALD

Question 4

ALD: rough threshold and paradox

Answer 4

80g/day men, 20g/day women –> ALD; less than 20% of men who consume too much alcohol become cirrhotic

Question 5

ALD: sx and signs

Answer 5

Wide range of symptoms (none –> florid liver failure); signs = jaundice, spider angiomata, hepatosplenomegaly

Question 6

ALD: disease course

Answer 6

Normal liver fatty liver alcoholic hepatitis (25%) –> cirrhosis (15%)

Question 7

Alcoholic hepatitis sx

Answer 7

Fever, tachycardia, high WBCs, AST > ALT, increased GGT, bili, portal HTN

Question 8

Fatty liver: consequence of ______, histo appearance, reversibility

Answer 8

Consequence of alcohol oxidation w/ excess lipid stored in large droplets w/in hepatocytes (benign, reversible)

Question 9

Alcoholic hepatitis: histo, term

Answer 9

Steatosis, hepatocellular necrosis and acute inflammation (PMNs) most pronounced in Zone 3; Mallory’s hyaline bodies = ballooned w/ acetaldehyde

Question 10

Cirrhosis: histo, term

Answer 10

Deposition of collagen around terminal hepatic vein and sinusoids –> chicken wire pattern; micronodules if drinking and macronodules if abistenant (due to regeneration)

Question 11

ALD: transplantation

Answer 11

Acceptable tx in well selected indvs who demonstrate sustained (6 mo) abstinence

Question 12

NAFLD: how common in US

Answer 12

Up to 25% of US population

Question 13

Metabolic syndrome; NAFLD?

Answer 13

Abdominal obesity, high triglycerides, low HDL, HT, high fasting glucose; NAFLD is hepatic manifestation of metabolic syndrome

Question 14

NAFLD: spectrum NAFL –> NASH)

Answer 14

Steatosis –> steatosis with inflammation, ballooning, and perhaps fibrosis, Mallory’s hyaline, megamitochondria –> cirrhosis, HCC

Question 15

2-hit hypothesis

Answer 15

1st hit = steatosis, 2nd hit –> NASH

Question 16

NASH: histology for dx (3 requirements)

Answer 16

Necessary to see: steatosis in Zone 3, lobular inflammation, ballooned hepatocytes

Question 17

NASH: natural history (%)

Answer 17

15% improve, 40% stable, 40% fibrotic progression, 5% cirrhosis/cancer

Question 18

US Population % with >5.5% elevated liver fat

Answer 18

About 30%

Question 19

Associated syndromes with NAFLD

Answer 19

Diabetes (may precede diabetes), obesity (most obese have fatty livers), hyperlipidemia

Question 20

Other causes of NAFLD (3)

Answer 20

Drug induced, TPN, rapid weight loss –> GI surgery

Question 21

NAFLD: pathophysiology

Answer 21

Insulin resistance –> lipolysis/lipogenesis –> more adipocytes –> increased FFA in serum –> to liver for packaging/storage –> too much FFA overwhelms liver causing lipid peroxidation, ROS, inflammation, and fibrosis; also effect of adipokines (letptin)

Question 22

NAFLD: clinical presentation

Answer 22

Most are asymptomatic w/ liver enzyme elevation, fatty liver on imaging –> hepatomegaly (can cause pain) and fatigue –> fully symptomatic w/ cirrhosis and HCC

Question 23

NAFLD: dx

Answer 23

History taking, labs (ALT > AST), imaging

Question 24

NAFLD: imaging (how it looks on ultrasound, CT, MRI)

Answer 24

Ultrasound = bright; CT w/out contrast = liver less bright than spleen, MRI = diff signal intensity

Question 25

NAFLD: tx (3)

Answer 25

Control risk factors like weight loss, diabetes control, treat high lipids (statins, gemfibrozil)

Question 26

Is there a medication for NAFLD?

Answer 26

Nope