Lecture 21: Alcoholic and Nonalcoholic Fatty Liver Flashcards
How does someone wth ALD improve the state of their liver?
Abstinence
ALD: Gender differences
Gastric mucosal ADH lower in women –> greater hepatic exposure to alcohol
ALD: HCV/HBV interaction
Viral hepatitis worsens ALD
ALD: rough threshold and paradox
80g/day men, 20g/day women –> ALD; less than 20% of men who consume too much alcohol become cirrhotic
ALD: sx and signs
Wide range of symptoms (none –> florid liver failure); signs = jaundice, spider angiomata, hepatosplenomegaly
ALD: disease course
Normal liver fatty liver alcoholic hepatitis (25%) –> cirrhosis (15%)
Alcoholic hepatitis sx
Fever, tachycardia, high WBCs, AST > ALT, increased GGT, bili, portal HTN
Fatty liver: consequence of ______, histo appearance, reversibility
Consequence of alcohol oxidation w/ excess lipid stored in large droplets w/in hepatocytes (benign, reversible)
Alcoholic hepatitis: histo, term
Steatosis, hepatocellular necrosis and acute inflammation (PMNs) most pronounced in Zone 3; Mallory’s hyaline bodies = ballooned w/ acetaldehyde
Cirrhosis: histo, term
Deposition of collagen around terminal hepatic vein and sinusoids –> chicken wire pattern; micronodules if drinking and macronodules if abistenant (due to regeneration)
ALD: transplantation
Acceptable tx in well selected indvs who demonstrate sustained (6 mo) abstinence
NAFLD: how common in US
Up to 25% of US population
Metabolic syndrome; NAFLD?
Abdominal obesity, high triglycerides, low HDL, HT, high fasting glucose; NAFLD is hepatic manifestation of metabolic syndrome
NAFLD: spectrum NAFL –> NASH)
Steatosis –> steatosis with inflammation, ballooning, and perhaps fibrosis, Mallory’s hyaline, megamitochondria –> cirrhosis, HCC
2-hit hypothesis
1st hit = steatosis, 2nd hit –> NASH
NASH: histology for dx (3 requirements)
Necessary to see: steatosis in Zone 3, lobular inflammation, ballooned hepatocytes
NASH: natural history (%)
15% improve, 40% stable, 40% fibrotic progression, 5% cirrhosis/cancer
US Population % with >5.5% elevated liver fat
About 30%
Associated syndromes with NAFLD
Diabetes (may precede diabetes), obesity (most obese have fatty livers), hyperlipidemia
Other causes of NAFLD (3)
Drug induced, TPN, rapid weight loss –> GI surgery
NAFLD: pathophysiology
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)
NAFLD: clinical presentation
Most are asymptomatic w/ liver enzyme elevation, fatty liver on imaging –> hepatomegaly (can cause pain) and fatigue –> fully symptomatic w/ cirrhosis and HCC
NAFLD: dx
History taking, labs (ALT > AST), imaging
NAFLD: imaging (how it looks on ultrasound, CT, MRI)
Ultrasound = bright; CT w/out contrast = liver less bright than spleen, MRI = diff signal intensity
NAFLD: tx (3)
Control risk factors like weight loss, diabetes control, treat high lipids (statins, gemfibrozil)
Is there a medication for NAFLD?
Nope
