Occult lifelong persistence of infectious hepadnavirus and residual liver inflammation in woodchucks convalescent from acute viral hepatitis

Traces of hepatitis B virus (HBV) genome can persist for years following re covery from hepatitis B, To determine overall duration, molecular character istics, and pathological implications of this serologically undetectable fo rm of hepadnaviral carriage, we have analyzed the expression of transcripti onally active virus genomes, their infectivity, and examined liver alterati ons during the natural lifespan of woodchucks convalescent from acute infec tion with HBV-related woodchuck hepatitis virus (WHV), In this study, we do cument lifelong persistence of scanty amounts of replicating virus both in the liver and lymphatic system after spontaneous resolution of an episode o f experimental hepadnaviral hepatitis. Antibodies to virus nucleocapsid (co re) were found to be the most reliable immunovirological marker coexisting with occult infection. In the majority of convalescent woodchucks, serial l iver biopsies showed protracted minimal to mild necroinflammation with peri ods of normal morphology; however, hepatocellular carcinoma (HCC) ultimatel y developed in 2 of 9 animals studied. Inocula derived from lymphoid cells of convalescent animals induced classical acute hepatitis in virus-naive wo odchucks that progressed to chronic hepatitis and HCC in 1 of the animals, demonstrating infectivity and pathogenic competence of the carried virus, O ur results reveal that low levels of infectious WHV and residual hepatic in flammation usually continue for life after resolution of hepatitis and that this recovery does not avert HCC development. They also demonstrate that, in addition to the liver, the lymphatic system is the site of the occult li felong maintenance of replicating hepadnavirus.