Hepatocyte demand and substrate supply as factors in the susceptibility to alcoholic liver injury: pathogenesis and prevention.

In conclusion, the studies presented suggest that two factors commonly occurring in the alcoholic, namely, an increased rate of ethanol metabolism and hepatomegaly, may have important pathogenic implications in alcoholic liver disease. An increased rate of ethanol metabolism is linked to a greater oxygen demand, thus resulting in greater susceptibility to hypoxia in Zone 3 of the liver acinus, a factor which might be responsible for hepatocellular necrosis in alcoholic hepatitis. Propylthiouracil has been shown to have a protective effect against hypoxic necrosis in alcohol-fed animals and has been found to be most effective in accelerating the rate of recovery of alcoholics with active liver disease. On the other hand, hepatocyte expansion in hepatomegaly, in the face of a semi-rigid liver capsule, leads to constriction of extracellular volume and to an increase in intrahepatic and portal pressure. The latter, in turn, could produce a variety of haemodynamic alterations as those found in the alcoholic. To what extent the mechanisms described are responsible for or might add to the myriad of other disturbances observed in alcoholic disease should be further analysed.