Alcoholic liver disease causes
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Causes
Fatty change and alcoholic hepatitis are probably reversible. The later stages of fibrosis and cirrhosis tend to be irreversible but can usually be quite well managed for long periods of time.
The cause of fatty change are:
- The excess generation of NAD by the enzymes alcohol dehydrogenase and aldehyde dehydrogenase which cause shunting of normal substrates from catabolism towards lipid biosynthesis.
- Impaired assembly and secretion of lipoproteins and increased peripheral lipid catabolism may also contribute
The cause of alcoholic hepatitis are:
- Acetaldehyde formed from alcohol induces lipid peroxidation and acetaldehyde protein adduct formation which disrupt cytoskeleton
- Directly affect microtubule organization, mitochondrial function and membrane fluidity
- Generation of ROS
- Neutrophil attack at the site of hepatocyte necrosis
Fatty change
- Fatty change, or steatosis is the accumulation of fat in liver cells which can be seen as fatty globules under the microscope.
- Alcoholism causes large fatty globules (macrovesicular steatosis).
- Other causes of macrovesicular steatosis include diabetes, obesity and starvation.
- Alcoholic fatty change is probably dose related.
- Small fatty globules have different causes.
Alcoholic hepatitis
- Some people get an acute hepatitis or inflammatory reaction to the cells affected by fatty change. This is not directly related to the dose of alcohol.
- Some people seem more prone to this reaction than others. This is called alcoholic steatonecrosis and the inflammation probably predisposes to liver fibrosis.
Liver fibrosis
- Liver fibrosis, in itself, is largely asymptomatic but as it progresses it can turn into cirrhosis, where the fibrosis alters the architecture and impairs the function of the liver.
Cirrhosis
- Cirrhosis is a late stage of liver disease marked by fibrosis and altered liver architecture.
- It is often progressive and may eventually lead to liver failure.
- Late complications of cirrhosis or liver failure include portal hypertension, coagulation disorders, ascites and other complications including hepatic encephalopathy and the hepatorenal syndrome.
- Cirrhosis also has number of other causes, such as hepatitis and toxins. The late stages of cirrhosis (say from viral hepatitis or alcohol) may look similar. This phenomenon is termed a "final common pathway" for a disease.