As the majority of alcohol leaves the gastrointestinal tract, it travels via the hepatic portal vein from the small intestines to the liver, the largest organ in the body and the primary site of alcohol metabolism. Since some alcohol metabolites are toxic, and because the concentration of alcohol reaching the liver is so high and the liver is the primary site of alcohol metabolism, liver damage may be among the most likely and most serious physiological consequences of alcohol abuse. This is particularly significant because of the central role the liver plays in so many physiological activities. Epidemiological data clearly reveals that alcohol abuse is by far the leading cause of liver-related mortality in the United States. Excessive alcohol consumption leads to three serious types of liver injuries: fatty liver, hepatic inflammation (alcoholic hepatitis), and progressive liver scarring (fibrosis or cirrhosis).

Chronic heavy drinking can alter normal metabolism and lead to an accumulation of fat in the liver. As a result, the liver cells become infiltrated and the liver itself becomes enlarged. The bad news is that extensive lipid infiltration may damage cells. The good news is that fatty liver is reversible with abstinence.

Hepatitis is a more serious medical condition, characterized by prolific inflammation and tissue damage. Hepatitis is life-threatening but there can be significant recovery following abstinence. The most serious form of liver damage is cirrhosis. This irreversible liver disease is characterized by scarring and cell death. Impaired liver functioning can cause primary hepatic encephalopathy, a brain disorder characterized by altered psychomotor, intellectual, and behavioral functioning.

Although chronic, heavy drinking may produce metabolic tolerance and unusually high rates of alcohol elimination, hepatitis and fibrosis ultimately will impair liver function and produce a reverse metabolic tolerance and impaired oxidation of alcohol. Underreporting of alcohol consumption makes the exact prevalence of alcoholic liver disease in the United States difficult to measure, but health statistics suggest that some form of alcoholic liver disease affects more than 2 million drinkers (Dufour et al., 1993). It is estimated that 900,000 Americans have cirrhosis, and of the 26,000 who die each year, 40 to 90 percent have a history of alcohol abuse (Dufour et al.,
1993).

It is clear that the development of alcoholic liver disease is due to a combination of factors, most notably, prolonged alcohol consumption. One commonly asked question by both scientists and concerned drinkers is “How much alcohol does one need to drink before liver damage occurs?” Epidemiological studies suggest that reliable signs of injury begin after a “threshold” dose of alcohol is reached. Although there are always individual exceptions, the evidence suggests that the threshold is equal to a cumulative dose of about 600 kilograms for men, and between 150 and 300 kilograms
for women. To place this in perspective, at the high end (for men), this is roughly equivalent to the average consumption of 10 to 12 drinks a day for ten years, and at the low end (for women), about three drinks per day . Below these doses, it is difficult (but certainly not impossible) to reliably detect liver injury (Lelbach, 1975; Marbet et al., 1987; Mezey et al., 1988; Tuyns and Pequignot, 1984), or the damage is not significant enough to warrant medical attention. The differences in threshold doses between men andwomen cannot be accounted for by anthropometrics or pharmacokinetics. In addition, many individuals who consume these amounts of alcohol never develop liver disease and less than one-half of heavy drinkers develop alcoholic hepatitis or liver fibrosis (Lelbach, 1975).

This suggests that alcohol does not produce its effects independently and that hereditary and/or environmental factors interact with alcohol to affect the natural history of liver injury (Marbet et al., 1987). Marbet and colleagues suggested that other factors contribute to the pathogenesis of liver disease in alcoholics because even though a substantial amount of alcohol is required to induce liver injury, alcohol dose alone is not a good predictor of the severity of liver injury (Marbet et al., 1987).
Numerous possible mechanisms may affect the susceptibility of certain people to alcohol-induced liver damage, but the exact mechanisms by which chronic alcohol abuse leads to liver disease are not known. A number of mechanisms have been suggested which will be briefly reviewed below.