Alcoholic Liver Disease

Alcoholic liver disease remains a major primary cause of chronic liver disease in the United States and worldwide. Furthermore, alcohol is commonly implicated as a major exacerbating factor in many other liver diseases, such as hepatitis C, nonalcoholic fatty liver disease, and hemochromatosis, and therefore may play a role in a significant proportion of patients with acute and/or chronic liver disease.

Despite enormous progress in the past several decades, several key aspects of alcoholic liver disease remain unexplained, perhaps most importantly, the great variability in the relationship between quantity of alcohol consumed and risk for liver damage. However, it is generally recognized that the typical threshold level of alcohol intake associated with liver disease is 60 g daily over a 10-year period. The threshold for alcoholic liver disease is much lower among women than among men. Factors associated with this phenomenon may include the lighter body weight of women and decreased gastric alcohol dehydrogenase activity.

The pathophysiology of alcoholic liver disease is multifactorial. Numerous factors have been proposed, including genetic factors, toxic effects of alcohol, effect of prooxidant cytochromes (e.g., CYP 2E1), hypoxia, immune activation, and concomitant conditions (e.g., obesity). A key step in the metabolism of alcohol is the production of acetaldehyde, a hepatotoxin that mediates many steps in the evolution of hepatic necroinflammation in alcoholic liver disease. Stellate cell activation is central to the process of fibrogenesis. Over time, it can lead to the development of cirrhosis.

Clinical Picture

Clinical features of alcoholic liver disease are similar to other causes of liver disease, with some exceptions. Alcoholic liver disease is often associated with more prominent ascites in patients with otherwise-compensated liver disease. Serum liver biochemical tests may also point to a diagnosis of alcoholic liver disease because the aspartate transaminase (AST)/alanine transaminase (ALT) ratio is often greater than 2 : 1 and is frequently greater than 3 : 1.

The role of liver biopsy remains controversial in alcoholic liver disease. Some argue that biopsy should be routinely performed because occasionally, other unexpected causes of liver disease can be found in patients given a presumptive diagnosis of alcoholic liver disease ( Fig. 159.1 ). Histologic features of alcoholic liver disease may follow one of three patterns: fatty liver ( Fig. 159.2 ), alcoholic hepatitis, and alcoholic cirrhosis ( Fig. 159.3 ). Frequently, all three of these findings can be found in the same patient. In addition, there may be features of ballooning degeneration of hepatocytes, Mallory (hyaline) bodies, and variable degrees of fibrosis. In contrast to patients with nonalcoholic fatty liver disease, lobular damage, Mallory bodies, periportal or bridging fibrosis, and cirrhosis are observed in a much higher proportion of patients.