108 CHOLINE 



and that "This experimental cirrhosis is not identifiable with any of the 

 previously descril)ed experimental toxogenic cirrhoses nor with any of the 

 usual varieties of hepatic cirrhosis in man." If these statements were sup- 

 ported by the available facts, it would indeed be rash to assume that choline- 

 deficiency cirrhosis in rats bears any true relation to alcoholic cirrhosis in 

 man. But there is evidence that differences in the histopathology of the 

 two lesions are more apparent than real, and that in fact they can be re- 

 garded as minor variants of a fundamentally identical pattern. The impor- 

 tance of this question in any discussion of the pathology of choline deficiency 

 in man is self-evident, and it will therefore be considered in some detail. 



Cirrhosis in choline-deficient rats has been said to differ from that in 

 human alcoholics in the following essentials : (a) Usually there are abundant 

 amounts of stainable fat in the cirrhotic rat's liver, whereas frequently little 

 can be demonstrated in the alcoholic patient's liver at autopsy, (b) Ceroid 

 is often deposited in the livers of choline-deficient rats,^^^ whereas this pig- 

 ment is absent or present in only small amounts in alcoholic cirrhosis. ''-^■^-^ 

 (c) The cirrhosis of alcoholism is described as "portal"; that in choline- 

 deficient rats as "non-portal." These points will be considered in turn. 



1. Stainable Fat 



Stainable fat in cirrhotic livers of alcoholics, although a common finding, 

 is not constantly present at autopsy. This has been responsible for the con- 

 cept that this type of cirrhosis may not have been preceded by fatty paren- 

 chymal change. Although stainable fat may be absent from the liver of an 

 alcoholic at autopsy, there is much to suggest that abundant lipid might 

 have been demonstrable at an earlier, more actively progressive stage in 

 the development of the lesion. The fat content of cirrhotic livers at autopsy 

 and in the animal experiments has been shown to be inversely proportional 

 to the degree of fibrosis."*'" ■ ^'^ This is true also for the experimental cir- 

 rhosis produced in rats by a dietary deficiency of choline.'**^ In fact a stage 

 may be reached in the rat where, even though the animal has been main- 

 tained continuously on the low choline diet, microscopic examination fails 

 to reveal more than very small amounts of stainable fat in a liver that is 

 grossly cirrhotic (see Fig. 10). This indicates that much of the abnormal lipid 

 that accumulates in the liver must eventually escape or disappear even 

 in the absence of choline. The pathways by which this occurs may be ab- 

 normal and involve the biliary and vascular systems.^^' 



*" A. M. Pappenheimer and J. Victor, Am. J. Pathol. 22, 395-412 (1946). 



«8 H. Popper, P. Gyorgy, and H. Goldblatt, Arch. Pathol. 37, 161-168 (1944). 



4" W. S. Hartroft, Proc. Roy. College Phys. Surg. (Canada) pp. 120-138 (1949). 



«" C. L. Connor, Am. J. Pathol. 14, 347-364 (1938). 



"1 I. L. Chaikoff, C. L. Connor, and G. R. Biskind, Am. J. Pathol. 14, 101-110 (1938). 



"2 C. C. Lucas, J. H. Ridout, and W. S. Hartroft, Unpublished data (1952). 



"3 W. S. Hartroft and J. H. Ridout, Am. J. Pathol. 27, 951-990 (1951). 



