Liver Disease – (Cirrhosis of the Liver)
It has been estimated that alcoholism and alcohol related liver diseases affect over 10 million people per year in the United States, making it a major health problem. It is important to remember that alcohol related liver disease is quite often clinically silent, and its frequency is probably underestimated. In one recent series in which 90 healthy subjects were found to have minor transaminase elevations incidentally (routine physicals, blood donor screening, etc.), subsequent evaluation revealed evidence strongly suggestive of alcohol related liver disease in 23 (26%).
The exact mechanism of alcohol related damage remains a mystery. It is clear that the old concept that nutritional deficiency was of primary importance is incorrect. Experimental and clinical evidence exists demonstrating that significant alcohol related damage does occur despite maintenance of adequate nutrition. Most interest has centered on the possibility that some product of the metabolism of alcohol might be the culprit. Chief among these is acetaldehyde (uh-see-tal-dih-hide). Individual differences in the metabolic pathways might account for the observation that not all alcoholics develop significant liver damage.
Alcohol related liver disease is frequently subterranean from the standpoint of the clinical laboratory as well. Even in the cirrhotic (seer-ah-tick) patient there may be minimal or no alterations in the usual laboratory tests. Transaminase elevations may be very mild. Typical values for the aspartate aminotransferase (AST) tend to hover around 100 IU/L level. If the levels are greatly increased, one should suspect a complicating process (such as an adverse reaction to acetaminophen, (uh-see-tuh-men-oh-fin) to which alcoholics are particularly susceptible) or a variation on the nature of the alcohol induced disease (such as foamy degeneration). The alanine aminotransferase (ALT) is less affected by alcohol than is the AST. In fact, an AST/ALT ratio of greater than 2 is very helpful in distinguishing alcohol related liver disease from viral hepatitis, in which the ratio is usually less than one; the ratio does not clearly distinguish alcohol related liver disease from nonalcoholic steatohepatitis (stee-at-toe). The gamma glutamyl (gloot-uh-mill) transpeptidase, an enzyme induced by alcohol, is frequently elevated out of proportion to the alkaline phosphatase in alcohol related liver disease, but false positives and false negatives make this test less useful. Elevated levels of serum iron, percent transferrin saturation, and ferritin are frequent in alcohol related liver disease, at times leading to the mistaken clinical impression of hereditary hemochromatosis (hemo-kroma). These values significantly overestimate the amount of hemosiderin actually seen in the liver biopsies from these patients. Hematologic abnormalities, particularly macrocytosis related to folate deficiency are also useful. Blood or urine alcohol levels may provide a very direct indicator of the underlying problem.
Patterns of Injury
There are three classic patterns of injury that have been described with alcohol exposure. These are: fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. There are a number of variations that have been described as biopsy experience has grown and careful clinical pathological correlations have been done. In terms of the classic patterns, it has been estimated that 90% or more of alcoholics will develop fatty liver, making it essentially a physiologic effect of alcohol. Only some 10 to 35% will be shown to have alcoholic hepatitis as the time of biopsy, and about 10% will have cirrhosis. It appears as if most patients with alcohol related liver disease pass through a progression of fatty liver, alcoholic hepatitis, and finally cirrhosis over a number of years. However, a number of patients clearly develop cirrhosis without an overt stage of alcoholic hepatitis; it is not uncommon for an asymptomatic alcoholic to be found incidentally to have well established cirrhosis.
Fatty liver – It is very important to keep in mind that fatty change in the liver does not equate with alcohol exposure. The causes of fatty change in the liver are legion, and the most common cause may be obesity or diabetes rather than alcohol, depending on the population studied. Steatosis occurs in the livers of alcoholics due to a decreased rate of disposition secondary to impaired mitochondrial oxidation of lipid. Increased mobilization of fat from peripheral deposits and some degree of increased synthesis may also be contributory.
DISCLAIMER: The information provided here is for general informational purposes only, and is provided as a supplement for students enrolled in Meditec’s medical career training courses. The information should NOT be used for actual diagnostic or treatment purposes or in lieu of diagnosis or treatment by a licensed physician.