Newer concepts of cirrhosis.
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Biomedical subjects
Publications and source records attributed to G KLATSKIN.
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Rats maintained for a period of 7 months on a fluid intake of 15 per cent alcohol and a diet marginal in lipotropic activity developed fatty infiltration and mild fibrosis of the liver. Similar changes were observed in pair-fed controls given an isocaloric equivalent of sucrose instead of alcohol, but not in pair-fed controls receiving neither alcohol nor sucrose supplements. To exclude the possibility that the alcohol effect was related to an augmentation of the caloric intake, a third group of controls was given the same amount of alcohol, but a limited number of calories. This was accomplished by subtracting from the basal diet an amount of sucrose equivalent in calories to the alcohol consumed. Under these conditions the hepatic changes following alcohol ingestion appeared to be enhanced. Choline or methionine, on the other hand, abolished the effects of both alcohol and sucrose supplements. There was no increase in fecal nitrogen excretion following alcohol ingestion, and no histological changes were observed in the pancreas. These results are consistent with the hypothesis that alcohol increases the choline requirement of the rat, but do not support the contention that this effect is the consequence of an augmented caloric intake. Further studies are needed to establish conclusively the relationship between alcohol ingestion and the choline requirement, and to elucidate the mechanisms involved.
The effect of alcohol on the choline requirement was assayed in weanling rats maintained on a basal diet of relatively low lipotropic activity containing the equivalent of 0.089 per cent choline. Alcohol was administered as a 15 per cent solution in lieu of drinking water. The incidence of renal cortical necrosis, the increase in kidney weight, and the mortality rate at the end of 14 days served as indices of choline deficiency. Under these conditions alcohol-fed animals developed more severe signs of choline deficiency than either pair-fed controls or pair-fed isocaloric controls receiving a sucrose supplement instead of alcohol. The addition of as little as 0.08 per cent of choline to the basal diet abolished these differences. It was concluded that (a) alcohol increases the choline requirement, and may, thus, induce a state of relative deficiency when the diet is marginal in lipotropic activity, and (b) this effect is independent of the caloric intake. The possible significance of these observations in relation to chronic alcoholism in the pathogenesis of Laennec's cirrhosis has been discussed.
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