Toxic Liver Disease

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Alcohol is the most common cause of chronic liver disease.
Alcohol abuse is the most common cause of liver disease in Western countries, and women are more
prone to alcohol-induced liver damage than men.
Alcohol is an hepatotoxin and liver damage is related to daily alcohol intake. There is no safe lower
limit for alcohol ingestion, but maximum recommended daily intakes have been defined when the risk of
liver damage is thought to be small (50-60 g per day in males; 30-40 g per day in females).
Toxicity of ethanol is probably due to generation of its metabolic breakdown product acetaldehyde.
Alcohol causes fatty liver, acute hepatitis and cirrhosis.
Alcoholic liver damage may lead to fatty liver, in which the accumulation of fat in hepatocytes
is reversible with abstinence.
In acute alcoholic hepatitis, ingestion of large amounts of alcohol causes a true hepatitis,
with focal necrosis of liver cells. The illness resembles acute viral hepatitis, and liver function
tests show raised levels of transaminases and gamma-glutamyl trans-peptidase.
If a patient with alcoholic hepatitis abstains, the inflammation resolves without harm. With continued
ingestion of alcohol, fibrosis develops around central veins, and in response to continued hepatocyte necrosis.

The end-result is hepatic fibrosis that may progress to cirrhosis.
Alcoholic cirrhosis affects fewer than 10% of patients suffering from chronic alcoholism. It may
develop after episodes of acute alcoholic hepatitis or may be insidious in its onset, presenting only as
end-stage liver disease .
Liver biopsy shows fatty change and focal necrosis of liver cells associated with neutrophil infiltration
adjacent to dead cells. Mallory's hyaline accumulates in a small proportion of hepatocytes. Composed of
cytokeratin intermediate filaments, ubiquitin and a b crystallin, it appears as brightly eosinophilic
globules in liver cell cytoplasm. Although commonly seen in alcoholic hepatitis, it may also be seen in
association with other forms of hepatic damage.

Drugs are an important and common cause of liver disease
Drugs are a very common cause of liver disease, and a careful drug history is a vital part of assessment
of any patient with abnormal liver function. Hepatotoxic drugs may be divided into two main groups: intrinsic
hepatotoxins, which are dose-dependent, predictable, and are responsible for a high incidence of toxic damage to liver; and idiosyncratic hepatotoxins, which cause liver disease in a small percentage of exposed individuals, either because of hypersensitivity or abnormal drug metabolism.

All types of liver pathology may be caused by drugs, In view of the fact that almost any drug
can cause liver disease,it is advisable to consult a specialist text when relatinga drug
history to potential hepatic damage.
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Revised: 02-11-2014.