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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 |
