Alcoholic Liver Disease

Formation of the different stages of alcoholic liver disease depends on the amount and the duration of alcohol intake.

- Short term, up to 80 grams of reversible hepatic changes e.g. steatosis

- Daily, 80 grams or more leads to significant increase risk of severe liver injury

- 10 –15% of alcoholics develop cirrhosis

- Possible genetic susceptibility, but no reliable genetic markers as of yet

- Cirrhosis can occur independently of steatosis and steatohepatitis

Basically, there is no “safe” upper limit for alcohol consumption.

HepatotoxicityPathology

Steatosis results from:

- Excessive alcohol intake shifts the catabolism of alcohol towards lipid biosynthesis and fat accumulation in the liver

- Impaired the synthesis and secretion of lipoproteins

- Increase peripheral catabolism of fat

• Induction of cytochrome P-450 adds up to the transformation of other drugs to toxic metabolites

• Free radical formation from alcohol oxidation leads to cell injury

• Direct toxic effects of alcohol to mitochondrial function and cell membrane

• Acetaldehyde an intermediate metabolite causes disruption cytoskeletal and membrane dysfunction

Alternation of hepatic proteins induces immunological attack to hepatocytes

Induction of bacterial endotoxin into portal circulation from the gut

Liver Fibrosis Pathology

There is extensive collagen deposition by perisinusoidal hepatic stellate cells in response to:
• Kupffer cell activation and proinflammatory cytokines release

• Amplification of cytokines stimuli by platelet-activating factor released by endothelial cells and Kupffer cells

• Influx of neutrophils into hepatic parenchyma due to cytokines

Regional vasoconstriction

All these lead to:

1 – Liver Steatosis2 – Liver Hepatitis

3 – Progressive Liver Fibrosis

4 – Reduction in Liver Vascular Perfusion

Alcoholic Cirrhosis

This is the final and irreversible stage of alcoholic liver diseases, starting from hepatic steatosis, then alcoholic hepatitis which then leads to alcoholic cirrhosis.

Cirrhosis can develop more rapidly in the presence of steatohepatitis (1-2 years).

Liver Appearance

Initially large, tan, fatty liver, very heavy >2 kg

After years of chronic alcohol intake the liver becomes brown, shrunken, and non-fatty. With fibrosis the liver is light and does not weight much, <1 kg.

Microscopic Appearance

Three features are important to see in liver cirrhosis. These are:

Fibrosis

Hepatocytes regeneration

Architectural distortion
Delicate fibrous bands run within the lobules, sinusoidal and central veins

Portal to portal fibrosis

Entrapped hepatocytes degenerate and try to regenerate forming micronodules

Nodularity becomes more prominent with formation of thick fibrous septa and macronodular formation

Ischemic necrosis and extensive fibrosis lead to tough scar formation and subsequent Laënnec cirrhosis

Bile stasis and rare mallory bodies may be present.

Remember that common end stage cirrhosis is independent to the cause (ALD, viral hepatitis, PBC, others)

Hepatic steatosis

The liver is large, soft, yellow and greasy.

Microscopic features

Microscopic features depend on the amount of alcohol intake:

Microvesicular formation: small lipid droplets in hepatocytes

Macrovesicular formation: larger clear globules compressing and displacing hepatocytes’ nuclei to one end

Centralobular – entire lobule

No or minimal fibrosis around central vein

Reversible if the patient stops drinking