Biochemical Mechanisms of the Alcohol-Induced Liver Injury

Abstract

1. The biochemical mechanisms of the alcohol-induced liver injury are reviewed. 2. Acute alcohol intake causes redox changes in pyridine nucleotides, a fatty liver and an exacerbation of hepatic porphyrias. 3. The redox changes are caused by alcohol metabolism, and it is hoped that substances other than fructose, which are known to accelerate alcohol metabolism, will be tested clinically in acute alcoholic intoxication. 4. The acute fatty liver is produced by an increased hepatic uptake of plasma free fatty acids secondary to enhanced hepatic blood flow, an activation of phosphatidate phosphohydrolase and a possible hypermobilization of adipose-tissue fat. 5. The alcohol exacerbation of hepatic porphyrias may be due to the further removal of the regulatory haem pool controlling haem biosynthesis. 6. Chronic alcohol intake causes redox changes similar to those mentioned above, a fatty liver and hepatitis, cirrhosis and necrosis. 7. The redox change in the NADP couple is caused by that in the NAD couple. 8. The chronic fatty liver is produced mainly by an increased esterification of fatty acids. Dietary fat plays an important role, and factors such as increased hepatic uptake of plasma free fatty acids and activation of phosphohydrolase may also be involved. 9. We know very little about the biochemical pathology of the alcoholic hepatitis and cirrhosis. 10. In experimental animals, chronic alcohol consumption causes hepatic-cell necrosis if the liver is either exposed to a high concentration of alcohol or if made anoxic by exposing the animals to low oxygen atmospheres or by bleeding. 11. There is evidence that acetaldehyde may be involved in some of the hepatotoxic effects of alcohol. 12. Alcohol also causes lipid peroxidation and the possibility that destruction of membrane phospholipid is involved in the hepatotoxicity of alcohol cannot be ruled out.