Morphology of Alcoholic Liver Disease

Alcoholic Liver Disease (ALD) is a term used to describe the spectrum of liver injury associated with acute andchronic alcoholism.

The 3 stages of Alcoholic Liver Disease are:

1. Hepatic steatosis (fatty change)
2. Alcoholic hepatitis
3. Alcoholic cirrhosis

Interrelationships among stages of Alcoholic Liver Disease:

Gross appearance of Normal Liver:

Weighing 1200-1600 grams

Reddish brown in color

Soft in consistency

Smooth surface

Microscopic examination of Normal Liver and Hepatocytes:

Hepatic Steatosis:

Steatosis is a condition characterized by abnormal accumulations of triglycerides within parenchymal cells. Hepatic steatosis (fatty change) is reversible even when extensive.

Gross appearance:

No gross change occurs with mild steatosis. Later, the liver is:

1. Soft
2. Yellow
3. Greasy
4. Large (up to 4 to 6 kg)

Microscopic examination:

1. Moderate alcohol intake: small (microvesicular) lipid droplets acculmulate in hepatocytes that doesn’t compress and displace nucleus to periphery
2. Chronic alcohol intake: large (macrovesicular) globules, compressing and displacing the nucleus to the periphery of hepatocytes
3. Initially, cell damage produces centrilobular fat depositions.
4. But in severe cases entire lobule may be involved.
5. Little or no perivenular fibrosis

Alcoholic Hepatitis

Alcoholic hepatitis develops acutely, usually following a bout of heavy drinking. In 10% to 35% of heavy drinkers, alcoholic hepatitis is superimposed on pre-existing hepatic steatosis increasing the risk of cirrhosis.

Gross appearance:

The liver is:

1. Mottled red with bile stained areas
2. Of normal or increased size
3. Often contains visible nodules and fibrosis

Microscopic examination:

1. Hepatocyte swelling (ballooning): due to accumulation of fat, water and protein.
2. Hepatocyte necrosis (ballooning degeneration) which attracts neutrophils
3. Mallory bodies (Cytokeratin aggresomes): Eosinophilic cytoplasmic inclusions in degenerating hepatocytes
4. Neutrophilic reaction: Neutrophils surround the mallory bodies like “jackals around a campfire”
5. Fibrosis: “Chicken wire” fibrosis surrounds the hepatocytes (sinusoidal, perivenular and ocassionaly periportal)

Alcoholic Cirrhosis:

Alcoholic cirrhosis is the final and irreversible form of alcoholic liver disease which usually evolves slowly and insidiously. Cirrhosis is a diffuse process (affecting whole liver) characterized by fibrosis and conversion of the liver architecture into nodules.

Gross appearance:

At Beginning: Micronodular (nodules <3cm in diameter), Yellow, Fatty, Enlarged (>2 kg)

After years: Macronodular (nodules >3cm in diameter), Brown, Non-fatty, Shrunken (<1 kg)

Microscopic examination:

1. Lobular architecture: No normal lobular architecture can be identified and central veins are hard to find.
2. Fibrous septa: The fibrous septa that divide the hepatic parenchyma into modules are initially delicate and extend through sinusoids from:
   • Central vein to portal regions and
   • Portal tract to portal tract
3. Hepatic parenchyma:
   • Hepatocyte regeneration generates micronodules (parenchyma shows extensive fatty change) .
   • As fibrous septa widens and surround nodules, liver becomes more fibrotic, loses fat and shrinks progressively in size.
   • Mixed micronodular and macronodular pattern seen
   • Laennec cirrhosis: Ischemic necrosis and fibrous obliteration of nodules create broad expanses of tough, pale, scar tissue.
4. Inflammation: Sparse infiltrate of mononuclear cells in the fibrous septa
5. Bile stasis

References:

1. Robins and Cotran Pathological Basis of Disease 7th edition
2. Robins Basic Pathology 8th edition
3. Textbook of Pathology by Harsh Mohan
4. Riede / Werner Color Atlas of Pathology – Thieme
5. Pathology Illustrated 6th Edition by Robin Reid and Fiona Roberts
6. Library.med.utah.edu

Prepared for Correlation Seminar for Gastrointestinal System in KIST Medical College by:

• Srijana Shakya (Roll no.79)
• Sulabh Shrestha (Roll no.80)