1989
DOI: 10.1002/hep.1840090321
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Hepatocellular carcinoma in woodchuck hepatitis virus-infected woodchucks: Presence of viral DNA in tumor tissue from chronic carriers and animals serologically recovered from acute infections

Abstract: During long-term studies of the natural history of woodchuck hepatitis virus infection, five cases of histologically confirmed, primary hepatocellular carcinoma were observed in a total of 92 woodchucks which had recovered, by analysis of viral serologic markers (WHsAg-, anti-WHc+, anti-WHs+), from experimental acute woodchuck hepatitis virus infections 20 to 30 months prior to the detection of hepatocellular carcinoma. No hepatocellular carcinoma was observed in 167 uninfected controls at least 3 years of age… Show more

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Cited by 140 publications
(80 citation statements)
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“…It also corroborates a previous report of HCC occurrence in woodchucks with recovery from acute WHV hepatitis. 16 In the human disease situation, circulating and integrated HBV-DNA sequences have been found in patients with serologically unidentified pathogenesis of HCC 13,15 and in the presence of hepatitis B surface antigen antibodies. 14,31 Low-level viremia persisted in all woodchucks investigated despite that 7 of them developed detectable anti-WHs, indicating that virus propagation progressed in the context of antivirus-specific humoral immunity.…”
Section: Discussionmentioning
confidence: 99%
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“…It also corroborates a previous report of HCC occurrence in woodchucks with recovery from acute WHV hepatitis. 16 In the human disease situation, circulating and integrated HBV-DNA sequences have been found in patients with serologically unidentified pathogenesis of HCC 13,15 and in the presence of hepatitis B surface antigen antibodies. 14,31 Low-level viremia persisted in all woodchucks investigated despite that 7 of them developed detectable anti-WHs, indicating that virus propagation progressed in the context of antivirus-specific humoral immunity.…”
Section: Discussionmentioning
confidence: 99%
“…This assumption is based on a growing number of observations indicating that HBV infection can appear in recipients of organs from HBV serologically negative donors, [7][8][9][10][11][12] and that hepatocellular carcinoma (HCC) with integrated HBV genomic sequences can arise in HBVseronegative patients 13-15 and animals. 16,17 There is also the likelihood that some individuals who develop subclinical infection after exposure to HBV become serologically silent carriers of virus and a potential source of infection to nonimmune humans.The main aims of this present study were to determine overall longevity and the sites of hidden hepadnavirus replication that continues after recovery from an episode of self-limited acute hepatitis (SLAH), to assess infectivity and pathogenic competence of the carried virus, and to recognize the long-term pathological consequences of this silent form of hepadnavirus infection. To circumvent practical and ethical difficulties associated with long-term study of individuals considered to be completely healthy, in particular with obtaining multiple liver biopsy samples, we have followed, for up to 6 years, woodchucks inoculated with woodchuck hepatitis virus (WHV), which is the closest relative of HBV among hepadnaviruses.…”
mentioning
confidence: 99%
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“…The involve- HBV-related HCC D Kremsdorf et al ment of HBV in HBsAg-negative liver cancers is also reinforced by two pieces of evidence. In the woodchuck HCC model, 17% of animals infected by WHV developed primary liver cancers, despite negativation of the assay for WHV surface antigen in the serum and the appearance of antibodies to surface and capsid viral antigens; furthermore, WHV DNA was detected in tumor tissue from these animals, with a much lower copy per cell number than in WHsAgpositive woodchucks (approximately 1 and 1000 molecules per cell, respectively) (Korba et al, 1989;Gerin et al, 1991), an observation fairly similar to that made in human HCCs. Ground squirrel may also prove to be an interesting model, as GSHV DNA sequences have been identified in HCCs developing in completely seronegative animals (Transy et al, 1992).…”
Section: Hbv-related Hcc D Kremsdorf Et Almentioning
confidence: 99%
“…WHV belongs to the genus Orthohepadnavirus (family: Hepadnaviridae), of which HBV is the prototype member. 11 Woodchucks with naturally acquired 12,13 or experimental 14,15 chronic WHV infection develop progressively severe chronic hepatitis and hepatocellular carcinoma (HCC), similar to the diseases observed in humans with chronic HBV infection. [11][12][13][14][15] The experiments reported here were designed to assess the antiviral activity of FIAU against WHV, and to determine the possible influence of hepadnavirus infection on toxicity by comparing the effects of FIAU in normal woodchucks and in chronic WHV carriers.…”
mentioning
confidence: 94%