Specificity and significance of hepatocellular ultrastructural changes in non-A, non-B hepatitis in chimpanzees

324 liver biopsies from 71 chimpanzees with and without non-A, non-B (NANB) hepatitis have been examined by electron microscopy (E.M.) for hepatocellular changes reported to be associated with this disease. At least 2 types of ultrastructural cytoplasmic alterations were found in each of 23 cases of acute and 6 cases of chronic NANB hepatitis. Nuclear modifications were never seen. Similar ultrastructural alterations were found in infections derived from 9 different human blood borne NANB cases. In 9 animals which had received 5 different inocula, Pfeifer Type I, II, III and IV changes were seen; 3 of the 4 types occurred in 10 animals and 2 of the types in 5 animals. Type II and III changes were almost always seen together. All 4 types of alteration were usually found in biopsies taken near the peak of ALT elevation. Five of 6 animals in whom E.M. changes were detected in serial samples over a 1 1/2 to 4 1/2 year period had concurrent chronic ALT abnormality. Two of these 6 animals did not develop ALT abnormality until years after the original acute episode though E.M. changes were detected throughout this period. There was generally a good correlation between onset and duration of ALT abnormality and period when E.M. changes were detected. All samples from animals not exposed to NANB virus(es) were negative by E.M. Our findings indicate the ultrastructural cytoplasmic alterations to be highly specific for NANB infection. Since each of the 9 isolates produced essentially the same pattern of E.M. changes, it is likely that a single NANB hepatitis virus group accounts for most blood borne NANB hepatitis.