Commentary on the Hypermetabolic State and the Role of Oxygen in Alcohol-Induced Liver Injury

  • Esteban Mezey


Centrilobular hypoxia has been postulated as a mechanism for the development of hepatocellular necrosis and fibrosis in alcoholic liver disease. Chronic ethanol ingestion in rodents results in increased hepatic oxygen consumption and in a steeper fall in oxygen tension between the periportal and the pericentral area of the lobule, rendering the pericentral area susceptible to hypoxia. Hepatocellular necrosis occurs when ethanol-fed animals are exposed to low atmospheric oxygen. In man, the existence of a hypermetabolic state is more tenuous, but suggested by an increased rate of ethanol elimination after chronic ethanol consumption that has been linked to increased oxygen consumption in animals. Also, decreases in hepatic blood flow and hepatic vein oxygen tension were found in alcoholics with histological evidence of liver-cell necrosis as compared to those without necrosis. It is postulated that in man, reduction in the availability of oxygen to the liver may be caused by miscellaneous conditions such as anemia, respiratory depression or infection, cigarette-smoking, or reduction of hepatic blood flow, but the contribution of one or more of these factors remains to be proven. Trials of the effect of propylthiouracil (PTU) on alcoholic hepatitis are based on the effect of this drug in decreasing the ethanol-induced hypermetabolic state and in preventing hepatocellular necrosis in animals exposed to low atmospheric oxygen. A tentative conclusion of the two small trials that have been completed is that PTU may be beneficial in moderately ill patients with a low mortality, but not useful in severely ill patients with a high mortality.


Alcoholic Liver Disease Hepatic Blood Flow Chronic Ethanol Alcoholic Hepatitis Increase Oxygen Consumption 
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Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Esteban Mezey
    • 1
  1. 1.Department of MedicineBaltimore City Hospitals, and The Johns Hopkins University School of MedicineBaltimoreUSA

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