Chronic and excessive alcohol ingestion is a major cause of liver disease and is responsible for nearly 50% of the mortality from all cirrhosis. The pathology of alcoholic liver disease consists of three major lesions, with the progressive injury rarely existing in a pure form: (1) fatty liver, (2) alcoholic hepatitis, and (3) cirrhosis. Fatty liver is present in >90% of daily as well as binge drinkers. A much smaller percentage of heavy drinkers will progress to alcoholic hepatitis, thought to be a precursor to cirrhosis. The prognosis of severe alcoholic liver disease is dismal; the mortality of patients with alcoholic hepatitis concurrent with cirrhosis is nearly 60% at 4 years. Although alcohol is considered a direct hepatotoxin, only between 10 and 20% of alcoholics will develop alcoholic hepatitis. The explanation for this apparent paradox is unclear but involves the complex interaction of facilitating factors such as drinking patterns, diet, obesity, and gender. There are no diagnostic tools that can predict individual susceptibility to alcoholic liver disease.
Alcohol is the world's third largest risk factor for disease burden. The harmful use of alcohol results in about 3.5 million deaths worldwide each year. Most of the mortality attributed to alcohol is secondary to cirrhosis. Mortality from cirrhosis is directly related to alcohol consumption, with the Eastern European countries the most significantly burdened. Cirrhosis and its complications are closely correlated with volume of alcohol consumed per capita population and are regardless of gender.
ETIOLOGY AND PATHOGENESIS
Quantity and duration of alcohol intake are the most important risk factors involved in the development of alcoholic liver disease (Table 335-1). The roles of beverage type(s), i.e., wine, beer, or spirits, and pattern of drinking (daily versus binge drinking) are less clear. Progress beyond the fatty liver stage seems to require additional risk factors that remain incompletely defined. Although there are genetic predispositions for alcoholism (Chap. 445), gender is a strong determinant for alcoholic liver disease. Women are more susceptible to alcoholic liver injury when compared to men. They develop advanced liver disease with substantially less alcohol intake. In general, the time it takes to develop liver disease is directly related to the amount of alcohol consumed. It is useful in estimating alcohol consumption to understand that one beer, four ounces of wine, or one ounce of 80% spirits all contain ~12 g of alcohol. The threshold for developing alcoholic liver disease is higher in men (>14 drinks per week), while women are at increased risk for liver injury by consuming >7 drinks per week. Gender-dependent differences result from poorly understood effects of estrogen, proportion of body fat, and the gastric metabolism of alcohol. Obesity, a high-fat diet, and the protective effect of coffee have been postulated to play a part in the development of the pathogenic process.
TABLE 335-1Risk Factors for ...