Pathogenesis of Alcoholic Liver Disease

Alcohol causes damage to the liver by various mechanisms which can be exacerbated by other factors.

Acetaldehyde – direct hepatocyte damage

Acetaldehyde concentration is increased in the liver with sustained alcohol intake resulting in hepatocytes becoming susceptible to hypoxia and hypoxic injury. Oxygen free radicals cause injury to hepatocytes by lipid peroxidation [1].

Genetics

Genetic factors have been implicated by studies which have found a relationship between ALD and polymorphisms of alcohol metabolising enzyme systems (ALDH2, Cytochrome p450) and cytokines (TNF╬▒, IL1, IL10) [3].

Acetate – altered carbohydrate metabolism

The metabolism of ethanol (alcohol) occurs in the mitochondria where it is oxidised to alcohol dehydrogenase. This is then oxidised to acetate by acetaldehyde dehydrogenase. These reactions alter the redox state of the cell and can have detrimental effects on lipid and carbohydrate delivery, metabolism and export from the liver causing triglyceride accumulation (fatty liver) [1,5].

Hepatitis C

Hepatitis C infection and alcohol have an additive effect together. This is thought to occur as alcohol may alter the immune system’s efforts at clearing the virus, or increased iron deposition in liver secondary to high levels of alcohol which may alter the pathophysiology of the virus [1].

Hepatitis C and ALD also increases the chance of developing hepatocellular carcinoma significantly [5].

Learning Bite

Development of ALD is mutifactorial and includes sex, hepatitis infections and genetics.

Inflammatory response

Acetaldehyde forms covalent bonds with proteins which are antigenic. Long-term exposure to alcohol causes the body to amass circulating antibodies to these proteins resulting in harmful humeral and cellular responses.

In alcoholic liver injury the expression of pro-inflammatory cytokines is up-regulated resulting in fibrosis [1]. Collagen is deposited in the space of disse which progresses to fibrosis and cell linkage formation resulting in cirrhosis. Lesions occur in the hepatic veins causing thickened veins and perisinusoidal fibrosis [5] which can lead to cirrhosis.

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