FURTHER OBSERVATIONS ON T H E PRODUCTION AND PREVENTION OF DIETARY HEPATIC INJURY IN RATS* BY PAUL GYORGY, M.D., AlUm

I t was first reported in 1939 (1) that hepatic injury, mainly in the form of acute zonal or diffuse necrosis, occurred irregularly in young rats fed a basal diet devoid of vitamin B (casein 18, cane sugar 68, melted butter fat 8, cod liver oil 2, salt mixture 4) and supplemented with thiamine, riboflavin, and pyridoxine. Thus, this ration was still deficient in several other members of the vitamin B complex, such as pantothenic acid, choline, and, as we know today, in several others (biotin, folic acid). In a group of more than 300 rats on this diet, 48 exhibited hepatic necrosis. In the livers of 4 rats, there was extensive fibrosis. Admittedly, even when hepatic injury in the form of necrosis was observed under apparently identical experimental conditions, it was found that it could not be produced at will and was not a regular occurrence. No proof for an infectious or exogenous toxic origin of the pathologic changes in the liver was found and the evidence suggested that the cause was nutritional. In this connection, it is particularly noteworthy that injury to the liver was never encountered in rats which, for from 3 to 6 months, had been fed the same basal diet deficient in the vitamin B complex and supplemented with yeast or crude yeast extract. On the other hand, in rats which, after having been kept on the vitamin B-deficient diet with supplements of thiamine, riboflavin, and pyridoxine (with or without choline), later developed manifestations of pantothenic acid deficiency and were then treated with pantothenic acid, zonal or massive necrosis has been observed. However, if such rats survived the first 4 weeks and showed gain in weight, or if other animals had from the start received all the supplements in question (thiamine, riboflavin, pyridoxine, pantothenic acid, and choline), they remained free from hepatic injury. From these many and varied observations, a common denominator emerged