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Robbins Liver & Biliary > Alcoholic Fatty Liver Disease > Flashcards

Alcoholic Fatty Liver Disease Flashcards

1
Q

What is the alcohol threshold per day for the development of fatty liver?

A

60g of alcohol per day

6 standard drinks

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2
Q

Alcohol affects the liver in different ways. What are the three outcomes of alcohol consumption on the liver?

A

Hepatic steatosis (fatty liver disease)

Alcoholic steatohepatitis

Cirrhosis

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3
Q

What is seen histologically in the liver after a small amount of alcohol consumption?

A

Microvesicular liquid fat droplets accumulating in the cytoplasm

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4
Q

What is seen histologically in the liver after a large amount of alcohol consumption?

A

Macrovesicular droplets

These can compress the nucleus and other organelles to the periphery of the cell

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5
Q

Macrcoscopically, how does alcoholic steatosis affect the liver?

A

Liver becomes enlarged (up to 4-6 kg)

Becomes yellow and greasy

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6
Q

If more alcohol is consumed when the liver is already in alcoholic steatosis, what change can occur morphologically?

A

Can develop fibrosis around the terminal hepatic veins

This fibrosis also can extend into the adjacent sinusoids

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7
Q

Is alcoholic steatosis reversible with discontinuation of alcohol consumption?

A

Yes, completely reversible

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8
Q

What histological changes occur in alcoholic steatohepatitis?

A

Hepatocyte swelling and necrosis

Mallory body formation

Neutrophilic reaction

Fibrosis

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9
Q

Why do hepatocytes undergo swelling in alcoholic steatohepatitis?

A

Accumulation of fat and water, as well as proteins that normally are exported

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10
Q

What can also contribute to hepatocyte dysfunction in alcoholic steatohepatitis?

A

Cholestasis

Mild deposition of haemosiderin

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11
Q

What are Mallory bodies?

A

Eosinophilic accumulations in hepatocytes

Composed of tangles of cytokeratin intermediate filaments, in complex with other proteins such as ubiquitin

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12
Q

Are Mallory bodies characteristic for alcoholic steatohepatitis?

A

No

Also present in NAFLD, PBC, Wilson disease, chronic cholestatic syndromes, and hepatocellular tumours

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13
Q

Why are neutrophils present in the liver parenchyma in alcoholic steatohepatitis?

A

Due to the degeneration of hepatocytes, particularly those with Mallory bodies

Presumably to phagocytose spilled contents after lysis

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14
Q

What cells lay down the fibrosis seen in alcoholic steatohepatitis?

A

Sinusoidal stellate cells

Portal tract fibroblasts

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15
Q

What are the typical locations of fibrosis in alcoholic steatohepatitis?

A

Sinusoidal and perivenular, separating parenchymal cells

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16
Q

When is periportal fibrosis seen in alcoholic steatohepatitis?

A

With repeated bouts of heavy alcohol intake

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17
Q

Is alcoholic steatohepatitis reversible with discontinuation of alcohol intake?

A

To some degree yes

18
Q

What is the final stage of liver disease with continued alcohol intake?

A

Cirrhosis

19
Q

How different is cirrhosis that forms after alcohol abuse, from cirrhosis due to other causes such as viral hepatitis?

A

Not different at all

20
Q

What alcohol intake is associated with the development of more severe alcohol related liver disease?

A

> 80g/day

21
Q

What alcohol intake is associated with the development of very severe alcohol related liver disease?

A

> 160g/day for decades

22
Q

What percentage of severe alcoholics develop cirrhosis?

A

10-15%

23
Q

What risk factors are there for the development of serious liver disease due to alcohol abuse?

A

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)

24
Q

What are 4 effects of alcohol on hepatocytes?

A

Oxidative stress

Steatosis

Mitochondrial and cellular membrane dysfunction

Hypoxia

25
Q

How does hepatocellular steatosis result from alcohol consumption?

A

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

26
Q

How does alcohol increase a hepatocyte’s sensitivity to ROS?

A

Alcohol induces metabolism of methionine, which leads to decreased glutathione levels

27
Q

How does alcohol consumption make other drugs more toxic/potent?

A

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)

28
Q

Does alcohol consumption affect the nutrition of a person?

A

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

29
Q

How does alcohol cause the release of pro-inflammatory cytokines in the liver?

A

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

30
Q

What are some signs of alcoholic hepatic steatosis?

A

Hepatomegaly

Potentially malaise, tenderness or discomfort in abdomen

31
Q

What are two common lab findings in alcoholic steatosis?

A

^ bilirubin and alkphos

32
Q

What are some symptoms of alcoholic steatohepatitis?

A

Malaise

Nausea

Low-grade fever

33
Q

What are some common signs of alcoholic steatohepatitis?

A

Febrile

Tachycardia

Mild tachypnea with primary respiratory alkalosis

Scleral icterus + dark urine

Asterixis

Ascites

Gynaecomastia, spider nevae

34
Q

What are some complications of alcoholic steatohepatitis?

A

Variceal haemorrhage

Hepatic encephalopathy

Coagulopathy/thrombocytopaenia (esp those with variceal bleeding)

Ascites (even without portal HTN as in other liver disease

Spontaneous bacterial peritonitis

35
Q

How can you treat the hepatic encephalopathy of alcoholic steatohepatitis?

A

Lactulose

36
Q

How can you treat variceal bleeding in alcoholic steatohepatitis?

A

Cessation of bleeding (sclerotherapy or banding ligation)

Drugs that reduce pressure within portal system (eg somatostatin (octreotide, lanreotide))

37
Q

How do you treat the ascites of alcoholic steatohepatitis?

A

Salt restriction

Diuretics (spironolactone + furosemide)

38
Q

What are useful lab measurements to do to diagnose alcoholic steatohepatitis?

A

C-reactive protein (sensitivity 41%, specificity 99%)

LFT (^ AST)

39
Q

Can steatosis occur in individuals who do not consume alcohol, or only consume it in low amounts?

A

Yes

Called non-alcoholic fatty liver disease (NAFLD)

40
Q

What are the similarities/differences between AFLD and NAFLD?

A

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

Robbins Liver & Biliary (6 decks)

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