Chapter 43

### Incidence & Pathogenesis

Chronic alcoholism is a major problem in almost every society (see also Chapter 12: Disorders Due to Chemical Agents). In developed countries, it has been estimated that about 10% of the population consume potentially harmful amounts of ethyl alcohol. The habit often begins in the teen years and continues throughout life. The incidence is increasing, and in developed countries chronic liver disease and accidents associated with alcoholism are among the 10 most common causes of death. Alcoholic liver disease is most common in middle-aged men, but there is an increasing incidence among women and in the young.

The greater the amount and the longer the duration of alcohol consumption, the greater the risk of liver disease. Most patients with chronic alcoholic liver disease have consumed about 150 g or more of ethyl alcohol daily for over 10 years (a standard 750 mL bottle of 80-proof whisky contains about 300 g of alcohol).

Not all heavy drinkers develop liver disease. About 50% of alcoholics have no detectable liver disease, 30% have alcoholic hepatitis, and 20% develop cirrhosis. Prediction of liver disease in individual cases is uncertain.

Alcohol is metabolized in the hepatocyte cytoplasm by the reduced nicotinamide adenine dinucleotide (NADH)-dependent enzyme alcohol dehydrogenase into acetaldehyde. Acetaldehyde or a related substance is believed to exert a toxic effect on liver cells. Malnutrition, which frequently coexists with alcoholism, may aggravate the liver injury.

### Clinicopathologic Syndromes

Alcoholic liver disease may be manifested as fatty liver, alcoholic hepatitis, or alcoholic cirrhosis (Figure 43-1). These lesions may coexist.

###### Figure 43–1.

Alcoholic liver disease. A: Fatty change. B: Acute alcoholic hepatitis (acute sclerosing hyaline necrosis). C: Chronic alcoholic liver disease, precirrhotic. D: Alcoholic cirrhosis.

#### Fatty Liver

(See Chapter 1: Cell Degeneration & Necrosis.) Fatty liver is a common early manifestation of alcohol injury. It is the result of decreased fatty acid oxidation, increased synthesis of triglycerides, and impaired secretion of lipoproteins by the liver cell. Fat accumulates first as small globules that coalesce, increasing in size and pushing the hepatocyte nucleus to one side.

Clinically, fatty liver causes diffuse liver enlargement. Liver function is normal even when there is severe fatty change. Fatty liver is reversible if the patient stops drinking at this stage.

#### Acute Alcoholic Hepatitis (Acute Sclerosing Hyaline Necrosis of the Liver)

Acute alcoholic hepatitis is characterized pathologically by (1) focal lytic necrosis of hepatocytes, causing an increase in serum enzyme levels; (2) cholestasis with jaundice; (3) neutrophilic infiltration of the sinusoids and around necrotic liver cells; (4) sclerosis around the central venule, initially as fine fibrils in the space of Disse and later as coarse fibrosis that may obliterate central veins; ...

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