Observations on the Conditions of Dietary Hepatic Injury (necrosis, Cirrhosis) in Rats*

I t was reported in 1939 (2) that hepatic injury, mainly in the form of acute focal or diffuse necrosis combined with fat infiltration, occurred irregularly in young rats fed a diet devoid of vitamin B (casein 18 per cent, cane sugar 68, melted butter fat 8, cod liver oil 2, salt mixture 4) and supplemented with thiamine, riboflavin, and pyridoxine. In a group of more than 300 rats, 48 exhibited hepatic changes of the type described. In livers of 4 of the rats there was diffuse periportal fibrosis. Admittedly, even when hepatic injury 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 toxic origin of the pathological changes in the liver could be found and the evidence favored, rather, a nutritional basis (2). 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 a diet deficient in the vitamin B complex and supplemented with thiamine, riboflavin, and 0.5 gin. of yeast daffy. Nor was hepatic injury found in investigations on riboflavin deficiency (3, 4) involving approximately 500 rats which were fed the same basal diet supplemented with thiamine and yeast extract in the form of Peters' eluate (5). As this hepatic disease was not prevented by the administration of thiamine, riboflavin, and pyridoxine, it was assumed (2) that the hypothetical factor which protected the liver must be one that was different from these components of the vitamin B complex. The incidence of hepatic injury remained practically unchanged in later groups of at least 250 rats 1 fed a vitamin B free diet, with daily supplements of 20 micrograms of thiamine, 20 to 25 micrograms of riboflavin, and 2 mg. of choline per gm. of diet (or 10 mg. of choline daily as a separate supplement)