Alcoholic Fatty Liver Disease Flashcards
What is the alcohol threshold per day for the development of fatty liver?
60g of alcohol per day
6 standard drinks
Alcohol affects the liver in different ways. What are the three outcomes of alcohol consumption on the liver?
Hepatic steatosis (fatty liver disease)
Alcoholic steatohepatitis
Cirrhosis
What is seen histologically in the liver after a small amount of alcohol consumption?
Microvesicular liquid fat droplets accumulating in the cytoplasm
What is seen histologically in the liver after a large amount of alcohol consumption?
Macrovesicular droplets
These can compress the nucleus and other organelles to the periphery of the cell
Macrcoscopically, how does alcoholic steatosis affect the liver?
Liver becomes enlarged (up to 4-6 kg)
Becomes yellow and greasy
If more alcohol is consumed when the liver is already in alcoholic steatosis, what change can occur morphologically?
Can develop fibrosis around the terminal hepatic veins
This fibrosis also can extend into the adjacent sinusoids
Is alcoholic steatosis reversible with discontinuation of alcohol consumption?
Yes, completely reversible
What histological changes occur in alcoholic steatohepatitis?
Hepatocyte swelling and necrosis
Mallory body formation
Neutrophilic reaction
Fibrosis
Why do hepatocytes undergo swelling in alcoholic steatohepatitis?
Accumulation of fat and water, as well as proteins that normally are exported
What can also contribute to hepatocyte dysfunction in alcoholic steatohepatitis?
Cholestasis
Mild deposition of haemosiderin
What are Mallory bodies?
Eosinophilic accumulations in hepatocytes
Composed of tangles of cytokeratin intermediate filaments, in complex with other proteins such as ubiquitin
Are Mallory bodies characteristic for alcoholic steatohepatitis?
No
Also present in NAFLD, PBC, Wilson disease, chronic cholestatic syndromes, and hepatocellular tumours
Why are neutrophils present in the liver parenchyma in alcoholic steatohepatitis?
Due to the degeneration of hepatocytes, particularly those with Mallory bodies
Presumably to phagocytose spilled contents after lysis
What cells lay down the fibrosis seen in alcoholic steatohepatitis?
Sinusoidal stellate cells
Portal tract fibroblasts
What are the typical locations of fibrosis in alcoholic steatohepatitis?
Sinusoidal and perivenular, separating parenchymal cells
When is periportal fibrosis seen in alcoholic steatohepatitis?
With repeated bouts of heavy alcohol intake
Is alcoholic steatohepatitis reversible with discontinuation of alcohol intake?
To some degree yes
What is the final stage of liver disease with continued alcohol intake?
Cirrhosis
How different is cirrhosis that forms after alcohol abuse, from cirrhosis due to other causes such as viral hepatitis?
Not different at all
What alcohol intake is associated with the development of more severe alcohol related liver disease?
> 80g/day
What alcohol intake is associated with the development of very severe alcohol related liver disease?
> 160g/day for decades
What percentage of severe alcoholics develop cirrhosis?
10-15%
What risk factors are there for the development of serious liver disease due to alcohol abuse?
Gender (women>men; more male patients though; ^ production of pro-inflammatory cytokines blamed)
Ethnicity (black > white; despite no difference in consumption)
Genetics (suggested by twin studies; aldehyde-dehydrogenase deficiency in Asians for example)
Co-morbidities (Haemochromatosis, HCV/HBV infection)
What are 4 effects of alcohol on hepatocytes?
Oxidative stress
Steatosis
Mitochondrial and cellular membrane dysfunction
Hypoxia
How does hepatocellular steatosis result from alcohol consumption?
Shunting of normal substrates away from catabolism and toward lipid synthesis due to excess NADH (from alcohol metabolism)
Impaired assembly and secretion of lipoproteins
Increased peripheral catabolism of fat
How does alcohol increase a hepatocyte’s sensitivity to ROS?
Alcohol induces metabolism of methionine, which leads to decreased glutathione levels
How does alcohol consumption make other drugs more toxic/potent?
Alcohol induces CYP2E1 and other P-450 enzymes increases alcohol catabolism in the ER
Also enhances the conversion of other drugs to toxic metabolites (eg paracetamol)
Does alcohol consumption affect the nutrition of a person?
Yes
Alcohol becomes a major sauce of calories in an alcoholic, leading them to neglect other foods and potentially leads to poor nutrition and lack of vitamins (esp thiamine)
Compounded by impaired digestive function related to mucosal damage
How does alcohol cause the release of pro-inflammatory cytokines in the liver?
Alcohol causes the release of bacterial endotoxin (LPS) from the gut into the portal circulation inducing inflammatory response
Includes activation of NF-kB, release of TNF, IL-6 and TGF-a
What are some signs of alcoholic hepatic steatosis?
Hepatomegaly
Potentially malaise, tenderness or discomfort in abdomen
What are two common lab findings in alcoholic steatosis?
^ bilirubin and alkphos
What are some symptoms of alcoholic steatohepatitis?
Malaise
Nausea
Low-grade fever
What are some common signs of alcoholic steatohepatitis?
Febrile
Tachycardia
Mild tachypnea with primary respiratory alkalosis
Scleral icterus + dark urine
Asterixis
Ascites
Gynaecomastia, spider nevae
What are some complications of alcoholic steatohepatitis?
Variceal haemorrhage
Hepatic encephalopathy
Coagulopathy/thrombocytopaenia (esp those with variceal bleeding)
Ascites (even without portal HTN as in other liver disease
Spontaneous bacterial peritonitis
How can you treat the hepatic encephalopathy of alcoholic steatohepatitis?
Lactulose
How can you treat variceal bleeding in alcoholic steatohepatitis?
Cessation of bleeding (sclerotherapy or banding ligation)
Drugs that reduce pressure within portal system (eg somatostatin (octreotide, lanreotide))
How do you treat the ascites of alcoholic steatohepatitis?
Salt restriction
Diuretics (spironolactone + furosemide)
What are useful lab measurements to do to diagnose alcoholic steatohepatitis?
C-reactive protein (sensitivity 41%, specificity 99%)
LFT (^ AST)
Can steatosis occur in individuals who do not consume alcohol, or only consume it in low amounts?
Yes
Called non-alcoholic fatty liver disease (NAFLD)
What are the similarities/differences between AFLD and NAFLD?
Similar histology and progression from steatosis to steatohepatitis
More pericellular fibrosis in NAFLD
No history of alcohol abuse in NAFLD, but association with metabolic disease, diabetes and obesity
