Excessive and regular alcohol consumption is the most important cause of major liver disease. Alcoholic liver disease comprises three major lesions, but purely only one form is very rare, they are (1) fatty liver, (2) alcoholic hepatitis, and (3) cirrhosis. Fatty liver is present in more than 90% of heavy drinkers. A small percentage of heavy and regular drinkers progress to alcoholic hepatitis, which is the precursor to cirrhosis of liver. The prognosis of severe alcoholic liver disease is very poor and by 4 years more than 60% die if there is alcoholic hepatitis with cirrhosis. Alcohol is a hepatotoxin but only 10 to 20 % of chronic alcoholics develop liver disease like hepatitis. This is not clear, and may be due to complex interaction of factors such as gender, heredity, and immunity.
Quantity and duration of alcohol intake are the most important risk factors in the development of alcoholic liver disease. The type of alcohol is less important than quantity and duration of alcohol consumption. Women are more susceptible to alcoholic liver injury compared to men. They develop liver disease with much less alcohol intake. Progress of the liver disease beyond the fatty liver stage requires additional risk factors that are not very clear. In general, the time taken to develop liver disease is directly related to the amount of alcohol consumed. The threshold for developing alcoholic liver disease in men is an intake of more than 60 to 80 g/d of alcohol for 10 years, while for women similar degrees of liver injury occurs by consuming 20 to 40 g/d for 10 years. So it is useful in estimating alcohol consumption to understand that one beer, four ounces of wine, or one ounce of 80% spirits all contains approximately 12 g of alcohol. Consumption of 160 g/d is associated with 25–fold increased risk of developing alcoholic cirrhosis. Higher toxicity of alcohol in women may be due to effects of estrogen and alcohol metabolism.
The following are the risk factors of development of Alcoholic Liver Disease:
Quantity: In men, 40–80 g/d of ethanol for 10 years produces fatty liver; 160 g/d for 10–20 years causes hepatitis or cirrhosis. But only 15% of alcoholics develop alcoholic liver disease.
Gender: liver injury occurs by consuming 20 to 40 g/d for 10 year in women.
Malnutrition: Alcohol injury does not require malnutrition, but obesity and fatty liver from the effect of carbohydrate metabolism and lipid synthesis and transport may be factors.
Hepatitis C: hepatitis C virus infection along with alcoholic liver disease is associated with younger age for severity, more advanced histology, decreased survival.
Genetics: Twin studies suggest that gene polymorphisms may include alcohol dehydrogenase (enzyme that metabolize alcohol), cytochrome P4502E1, and those associated with alcoholism.
Our understanding of the pathogenesis of alcoholic liver injury is incomplete. Alcohol is a direct hepatotoxin, but all the alcoholics do not develop alcoholic liver disease. Ingestion of alcohol also initiates a variety of metabolic responses that influence the final hepatotoxic response. Chronic infection with hepatitis C is important co morbidity in the progression of alcoholic liver disease to cirrhosis in chronic and excessive drinkers. Even moderate alcohol intake of 20 to 50 g/d increases the risk of cirrhosis and liver cancer in HCV infected individuals.
Tags: Gender, Hepatitis C virus, Hepatotoxin
