Pathological study of chronic D-galactosamine induced hepatitis in mice by administration of adjuvants - an animal model of the chronic active hepatitis.

An animal model for human chronic active hepatitis was created in inbred C-57 Black mice using prolonged (13 weeks) administration of D-Galactosamine (GalN) and adjuvants. Intraperitoneal injections of GalN (1,500 mg/kg) were repeated once a week. Simultaneously, Freund's complete adjuvant (FCA) was given subcutaneously to limbs. These mice showed a progressive inflammatory response; piecemeal necrosis of the portal area with marked cellular infiltration developed by the 13th week. The figure of severe liver cell degeneration and necrosis as well as lobular distortion and increased fibrous tissue closely resembled those in human chronic active hepatitis. Only a mild inflammatory response occurred in the groups given GalN alone or GalN with Freund's incomplete adjuvant. All mice given GalN wit BCG developed massive hepatic necrosis and died by the 4th week. Indirect immunofluorescent antibody detection technique showed little correlation between the disease activity and the presence of anti-liver cell membrane antibody in any of the group at the 13th week. The importance of the host immune reaction was indicated in the development of chronic hepatitis.