The livers of 33 captive woodchucks were examined histologically in 30 biopsy and 10 autopsy specimens and the findings were correlated with serum determinations for woodchuck hepatitis virus (WHV),
surface antigen (WHsAg) and antibody (anti-WHs), and WHV
DNA and
DNA polymerase. The liver appeared normal in all 3 serum-negative animals, 7 of 16 with indeterminate WHV status, and 1 of 4 with anti-WHs, but not in 10 animals with WHsAg, WHV
DNA, and
DNA polymerase. Mild hepatic
inflammation was found in 7 woodchucks with indeterminate status, 4 with anti-WHs, and 2 with each marker of WHV
infection. Significant
inflammation was found in 2 of indeterminate status and 4 with every marker, whereas more severe lesions (2 of chronic active type) occurred, almost always in autopsy specimens, in 8 animals with every marker. Eight of 10 animals with all markers had
orcein-positive inclusions (Shikata's technique) and 6 had
hepatocellular carcinoma associated with acute and chronic hepatic
inflammation and, usually, neoplastic nodules in the noncarcinomatous parenchyma. Features distinguishing the woodchuck lesion from human
hepatitis B disease were: association of
carcinoma with acute hepatic
inflammation (but not with
cirrhosis) and
DNA polymerase in the serum; transition to
carcinoma from neoplastic nodules; conspicuous plasma-cellular reaction of hepatic
inflammation, and hematopoietic cells in the
tumor. Significant hepatic lesions in the woodchucks were regularly associated with serum WHsAg, WHV
DNA, and
DNA polymerase. In contrast to man,
hepatocellular carcinoma in woodchucks was regularly associated with these markers of active viral replication. The nature of the
orcein-positive inclusions requires elucidation, although they may assist in screening for similar viruses in other species. The woodchuck may help in the study of the relation between
hepatocellular carcinoma and
hepatitis B, including the possibility of cocarcinogenic factors.