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Genetic and acquired factors that influence individual susceptibility to alcohol-associated liver disease.
As the title implies, the author reviews the known genetic and acquired factors that the determine the individual's susceptibility to develop alcohol-associated liver disease. Serving as a background for this discussion is the well-known fact that not all individuals consuming large amounts of alcohol develop cirrhosis. Also germane as background material is the knowledge that perivenular fibrosis at the fatty liver stage of alcoholic liver injury and alcoholic hepatitis are the precursor lesions for cirrhosis if drinking continues.

The genetic factors responsible for increased susceptibility to alcohol-induced cirrhosis include:

1) Female gender: This well-documented female predilection is probably attributable to the higher blood alcohol levels found in women when given corresponding equal amounts of alcohol as men.. The explanation for this appears to reside in the fact that in the female stomach there is decreased "first-pass" metabolism of ethanol because of decreased levels of alcoholic dehydrogenase.

2) Genetic predisposition to alcohol addiction: One group of authors feels that the presence of the dopamine Dreceptor gene, which is located on chromosome 11, may confer susceptibility to at least one for m of alcoholism.

3) Genetic polymorphism of enzymes of alcohol metabolism: As a result of this type of change, differences in the rate of alcohol metabolism may occur. This mechanism may very well be the explanation for racial differences in alcohol-induced liver disease. For example, many Orientals experience an "alcohol sensitivity" because of the rapid and sustained elevation of acetaldehyde produced by active, atypical alcohol metabolizing enzymes. This sensitivity is manifested as facial flushing, sweating, headache and increased pulse rate. This probably accounts for the low incidence of alcoholism in Orientals since the unpleasantness if the sensitivity acts as a deterrent against drinking.

4) Histocompatibility antigens.

5) Immunological factors: These could exert their influence on either an autoimmune basis or an enhanced immune response.

The acquired factors mentioned in the review include:

10 Nutritional factors, a deficiency of which amy contribute to the alcohol-associated injury.

2) Hepatitis B virus: Numerous studies have revealed an increased incidence of HBV infection in patients with alcoholic liver disease. In individuals positive with alcoholic for both states, cirrhosis develops at an earlier age and there is also shortened survival time.

3)Hepatitis C virus: One study suggested that HCV infection may have a role in the pathogenies of hepatocellular carcinomas in patients with chronic liver disease related to alcohol.

4) Drugs and toxins: Through various mechanisms, chronic alcohol ingestion is known to potentiate the acute toxicity of many drugs and toxins. These include carbon tetrachloride, acetaminophen, Vitamin A, opioids, cocaine, halothane, aflatoxin B, and methotrexate.

5) Hepatic siderosis: A mild degree of this is not uncommon in patients with alcoholic liver disease. MN

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