The significance of infections with two types of viral hepatitis demonstrated by histologic features in chimpanzees

Abstract

In view of the recognized importance of necroinflammatory episodes in chronic hepatitis B virus (HBV) infection, chimpanzees, either HBV surface antigen (HBsAg) carriers or noninfected (naive), were infected with other primary hepatotropic viruses to evaluate histologic alterations and changes in virologic and biochemical markers of infection. The advantages of studies on chimpanzees are the availability of serial biopsy specimens and the viral type-specific histologic lesions, not as well recognized in humans. Infection with hepatitis A and non-A, non-B (NANB) agents produced more severe lesions in chronic HBsAg carrier chimpanzees than in naive animals. During this superinfection, the specific expression of the second agent was predominant, indicating that the exacerbation is caused by the second agent, but that carriers are prone to more severe disease than the naive chimpanzees. Hepatitis delta virus (HDV) infections were always coexistant with HBV and superinfection of carriers produced histologic changes more severe than those seen in any other type of viral hepatitis. Such HDV infections revealed less evidence of lymphocytotoxicity but rather of cytotoxicity, and sometimes resembled in appearance the histopathology of NANB. Coinfection of HDV and HBV and superinfection of HBV-carriers with NANB resulted in hepatitis that was far less severe than superinfection of HDV in HBV carriers, greatly in keeping with human experiences. HBV replication was suppressed transiently in both NANB and HDV superinfection. This implies that in exacerbations during chronic HBV infections of humans, suppression of HBV replication markers indicates superinfection, for instance, by NANB for which markers are so far not widely available; by contrast, elevated markers of HBV replication suggest reactivation of the original HBV infection.