LIVER CHANGES IN HEPATOCEREBRAL DISEASE*

An attempt of pathogenetic analysis of Wilson's disease and Inose's disease, the two most important varieties of hepatocerebral diseases, was made from the facette of the hepatic pathology. The liver changes of a total of 43 human autopsy cases(19 of Wilson's and 24 of Inose's disease) were reevaluated. Concurrently an attempt of experimental production in animals of hepatic lesions compatible with those of Wilson's disease was made. Inose's special type of hepatocerebral disease is divided into two subgroups, a shunt form and a nutritional form. Cerebral damage in the shunt form is attributed to the portal-systemic collaterals, while the clinicopathological survey of the cases with the nutritional form indicates that functional disturbances, related unbalanced diet or endocrine abnormality, seem to cause brain damage. In Wilson's disease, three stages are noted from the analysis of the liver changes; fibrosis or monolobular cirrhosis in the first stage, submassive necrosis or active postnecrotic cirrhosis in the second stage and multilobular cirrhosis or arrested postnecrotic cirrhosis in the third stage. Experimentally, monolobular cirrhosis could be produced in animals by copper administration alone, whereas postnecrotic cirrhosis was first reproduced by a combination of copper administration and low protein diet, anti-kidney serum, or copper nephrosis. It is suggested that for the development of postnecrotic cirrhosis in the second and third stages of Wilson's disease an additional factor other than copper is needed, and that this second factor may be the deficiency of SH- containing aminoacids.