Experimental non-A, non-B hepatitis: four types of cytoplasmic alteration in hepatocytes of infected chimpanzees

On the occasion of an outbreak of non-A, non-B hepatitis in a plasmapheresis centre (81 cases, incubation period: 3–6 weeks) a pool of 12 plasma samples was obtained in the early phase of increasing transaminases. Two chimpanzees were inoculated, each receiving 12 ml of the pooled plasma. After an incubation period of 10–12 weeks a mild non-A, non-B hepatitis developed. Serum transaminases were slightly elevated. Needle biopsies, taken fortnightly, showed a slight activation of Kupffer cells (6–8 weeks), single cell necroses, and infiltration of the portal tracts (10–13 weeks). Electron microscopically four types of cytoplasmic change, were found in hepatocytes and assumed to be specific for the infection, Type I: Sponge-like inclusion (6 weeks after inoculation) composed of a dense matrix and irregularly arranged membranes. Type II: Attaching curved membranes (8 weeks), developing by close apposition of two cisternae of smooth endoplasmic reticulum. Type III: Cylindrical complexes (10 weeks), already described in literature. Type IV: Microtubular aggregates, usually neighbouring type III structures. The findings suggest 1) that the agent of the present infection is, at least in part, identical with that of the long incubation type of experimental non-A, non-B hepatitis, and 2) that ultrastructural alterations may precede manifest hepatitis.