Mayo Clin Proc 2001;76:1021; Postgrad Med J 2000;76:280

Cause: Excessive intake of ethanol. For practical purposes, alcohol has been defined in units. A unit is 1 oz of spirits, 12 oz of beer, or 4 oz of wine, and it contains about 10-12 gm of alcohol. Most individuals developing alcoholic liver disease (ALD) consume more than 35 units/week. A safe level of 21 units/week for men and 14 units/week for women has been proposed.

Epidem: Alcohol is the major cause of cirrhosis in Western countries. The risk of alcoholic liver disease is higher in those who consume >30 gm daily (Gut 1997;41:845), though only 5% of pts with this level of consumption have overt disease. Risk climbs markedly with increasing consumption. Female sex, drinking without food, binge drinking, and drinking concentrated beverages or multiple types of beverages increase risk. Coffee may be protective against cirrhosis (Arch IM 2006;166:1190).

Pathophys: Three forms of ALD are recognized. Steatosis (alcoholic fatty liver) occurs in 90-100% of heavy drinkers and is reversible with abstinence. In acute alcoholic hepatitis, there is hepatocyte ballooning and necrosis with cholestasis, but no evidence of cirrhosis. This occurs in about 10-35% of heavy drinkers. Alcoholic cirrhosis is the most severe form of injury and is seen in 8-20% of heavy drinkers. Histologically, there are bridges of fibrosis that develop between central veins and portal tracts. This creates a micronodular pattern of regenerating nodules.

Multiple factors are thought to mediate alcoholic liver injury (Postgrad Med 1998;103:261). Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase, and then to acetate. Changes that occur in the redox potential of the cell from this oxidation have harmful effects on lipids and carbohydrate metabolism. Acetaldehyde binds to proteins, creating antigenic targets and starting an inflammatory cascade. Iron deposition may play a role.

Sx: Many pts are asymptomatic and come to evaluation because of abnormal LFTs detected at a checkup or as part of an alcohol detoxification evaluation. Pts may have nonspecific complaints of anorexia, malaise, or abdominal pain, which are often related to their
alcoholism. The most crucial point is eliciting the alcohol hx. A variety of screening questionnaires have been developed. The CAGE questionnaire is widely used. It consists of 4 questions:

C: Have you ever felt the need to cut down your drinking?

A: Have you ever felt annoyed by criticism of your drinking?

G: Have you ever felt guilty about your drinking?

E: Have you ever taken a drink first thing in the morning (eye opener)?

Two or more positive responses suggest problem drinking. Pts often lie about their alcohol use, and hx from family members may be critical.

Si: In steatosis there is often hepatomegaly. In alcoholic hepatitis, the pt looks ill, and there may be fever, jaundice, spiders, tender hepatomegaly, ascites, or encephalopathy. Alcoholic cirrhosis causes signs of end-stage liver disease (p 26) that cannot be distinguished from signs caused by other liver diseases.

Crs: Five-yr survival in cirrhosis is 35-50%. Survival is much better in abstinent pts than in those who continue to drink. The prognosis in acute alcoholic hepatitis can be determined from laboratory parameters (see Lab).

Cmplc: HCC is a risk in cirrhotic pts (p 247). Any of the complications of end-stage liver disease may occur (p 255).

Diff Dx: The diff dx may be that of abnormal LFTs, cirrhosis, or jaundice (p 26).

Lab: LFTs, CBC with diff, and PT should be obtained. Transaminases are elevated in alcoholic hepatitis, usually in a pattern of AST > ALT with neither more than 7 × the upper limit of normal. GGTP is frequently elevated. In advanced disease, albumin drops and the PT is elevated. An elevated MCV can be a clue to alcoholism, and a random alcohol level can be informative. In alcoholic hepatitis, a severity score, called the discriminant function, is calculated as 4.6 × (pt’s PT – control PT) + bilirubin (mg/dL) (GE 1978;75:193). A score of >32 or spontaneous encephalopathy is associated with high mortality (>30%). Leukocytosis is common in alcoholic hepatitis. Thrombocytopenia can be seen with portal HTN or as a result of toxic effects of alcohol on bone marrow. Tests to exclude other causes of abnormal LFTs should be considered (p 28), and all pts should be tested for hep C. Liver bx is prognostic and can confirm the dx. It is usually notnecessary to perform bx.

X-ray: US should be performed to rule out obstruction or tumor. Pts with alcoholic cirrhosis may notdilate their bile ducts in response to obstruction (because of severe fibrosis), so caution in interpretation is warranted.