Transmission of Hepatitis B From Hepatitis-B-Seronegative Subjects

Thiers, Valérie; Kremsdorf, Dina; Schellekens, Huub; Goudeau, Alain; Sninsky, John J.; Nakajima, Etsuro; Mack, David H.; Driss, Françoise; Wands, Jack R.; Tiollais, Pierre; Bréchot, Christian

doi:10.1016/s0140-6736(88)92891-7

Cited by 311 publications

(134 citation statements)

References 17 publications

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“…32,39,40 These findings are consistent with our earlier reports of SOI continuing for life after termination of acute WHV hepatitis, 30,32,37 along with documented infectivity and liver pathogenic competence of the silently carried virus. 30,32 The current results also agree with the data from the limited studies of apparently healthy individuals reactive for anti-HBc alone or anti-HBc and anti-HBs, which showed presence of HBV cccDNA and HBV RNA in their liver 8,41 and transmission of HBV by liver grafts [15][16][17][18][19][20][21] or blood [42][43][44] to virusnaïve recipients.…”

Section: Discussionsupporting

confidence: 90%

Persistence of isolated antibodies to woodchuck hepatitis virus core antigen is indicative of occult infection

et al. 2004

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Antibodies against virus nucleocapsid (anticore) normally accompany hepadnaviral hepatitis but they may also occur in the absence of symptoms and other serological indicators of the infection. This situation can be encountered following a clinically and serologically unapparent exposure to hepatitis B virus (HBV) or after recovery from hepatitis B. In this study, woodchucks inoculated with woodchuck hepatitis virus (WHV) were investigated to determine the relationship between anticore detection and the molecular status of virus replication in a primary WHV surface antigen (WHsAg)-negative infection or long-after resolution of WHV hepatitis. Serial, parallel samples of sera, peripheral blood mononuclear cells (PBMC) and liver tissue, collected for more than 5 years after inoculation with virus, were examined for WHV DNA by highly sensitive polymerase chain reaction (PCR)/nucleic acid hybridization assays. Sera were also tested for WHV DNA after DNase treatment and for WHV DNA and WHsAg after concentration in sucrose. Liver and PBMC were examined for WHV covalently closed circular DNA and viral RNA transcripts by PCR-based techniques to assess virus replication status. The study showed that anticore antibodies existing in the absence of other serological markers are a reliable indicator of occult WHV infection. This state can be accompanied by traces of circulating particles behaving as intact virions and by intermittent minimal-to-mild liver inflammation. In conclusion, the long-term presence of anticore antibodies alone is a consequence of sustained restimulation of the immune system by virus nucleocapsid produced during low-level hepadnaviral assembly. ( A ntibodies to hepatits B virus (HBV) core antigen (anti-HBc) coexist with HBV surface antigen (HBsAg) in symptomatic infection and can persist along with antibodies to HBsAg (anti-HBs) or without them for life after recovery from hepatitis B. 1,2 They may also occur in the pre-acute phase of hepatitis prior to the appearance of HBsAg. 3 Absence of anti-HBc is rare in HBV infection and has been attributed to aberrant immunological response to the virus or to infection with viral variants. The detection of anti-HBc as the only serological marker of HBV exposure ("isolated anti-core" or "anti-core alone") has been found in up to 10%-20% of blood donors in endemic areas. 4,5 Since anti-HBc-like reactivity was occasionally seen after HBV vaccination, this result has raised doubts as to the reliability of antiHBc testing. 6,7 However, individuals with isolated antiHBc showed the highest rates of HBV DNA detection by specific polymerase chain reaction (PCR) assays, 5,8 -11 suggesting ongoing low-level HBV infection despite the absence of classical serological markers. This outcome was consistent with the earlier findings of anti-HBc along with HBV DNA in serum and peripheral blood mononuclear cells (PBMC) 12 and a vigorous cytotoxic T-lymphocyte response to HBV antigens in apparently completely healthy individuals years after recovery from

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Section: Discussionsupporting

confidence: 90%

Persistence of isolated antibodies to woodchuck hepatitis virus core antigen is indicative of occult infection

et al. 2004

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“…low levels of GSHV DNA in the tumors fror squirrels is reminiscent of the situation descri cases of HBV-infected humans (27)(28)(29) and ma established association between HCC developi squirrels and infection with GSHV (17,18).…”

Section: Discussionmentioning

confidence: 99%

Frequent amplification of c-myc in ground squirrel liver tumors associated with past or ongoing infection with a hepadnavirus.

Transy

Fourel

Robinson

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Persistent infection with hepatitis B virus (HBV) is a major cause of hepatoceliular carcinoma (HCC) in humans. HCC has also been observed in animals chronically infected with two other hepadnaviruses: ground squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus (WHV). A distinctive feature of WHV is the early onset of woodchuck tumors, which may be correlated with a direct role of the virus as an insertional mutagen of myc genes: c-myc, N-myc, and predominantly the woodchuck N-myc2 retroposon. In the present study, we searched for integrated GSHV DNA and genetic alterations ofmyc genes in ground squirrel HCCs. Viral integration into host DNA was detected in only 3/14 squirrel tumors and did not result in insertional activation of myc genes, despite the presence of a squirrel locus homologous to the woodchuck N-myc2 gene. This suggests that GSHV may differ from WHV in its reduced ability to induce mutagenic integration events. However, the high frequency of c-myc amplification (6/14) observed in ground squirrel HCCs indicates that myc genes might be preferential effectors in the tumorigenic processes associated with rodent hepadnaviruses, a feature not reported so far in HBV-induced carcinogenesis. Together with previous observations, our results suggest that hepadnaviruses, despite dose genetic and biological properties, may use different pathways in the genesis of liver cancer.

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“…HBV DNA analysis Selected oligonucleotide primers (Thiers et al, 1988) were synthesised using a DNA synthesiser apparatus (Gene assembler plus, Pharmacia). The primers 5'-CATCTTCTT-GTTGGTTCTTCTG-3' (Position 429-450) and 5'-TTAGG- (1 min).…”

Section: Methodsmentioning

confidence: 99%

High prevalence of mutations at codon 249 of the p53 gene in hepatocellular carcinomas from Senegal

Coursaget

Depril²,

Chabaud³

et al. 1993

Br J Cancer

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Summary In hepatocellular carcinoma, mutation within the p53 gene occurs mainly at codon 249 and its frequency has been associated with exposure to aflatoxin. As Senegal is a country where liver cancer incidence is one of the highest in the world and where people are highly exposed to aflatoxin, we screened 15 liver cancer samples from this country for mutation at codon 249 of the p53 gene.Non-tumoral DNA from the patients showed a wild type genotype. Mutation at codon 249 of the p53 gene was detected in 10 of the 15 tumour tissues tested (67%). This frequency of mutation in codon 249 of the p53 gene is the highest described. These results confirmed that there is an association between countries of high aflatoxin intake and a high frequency of mutation in codon 249 of p53 gene, and that HBV alone does not contribute to these base changes.

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Transmission of Hepatitis B From Hepatitis-B-Seronegative Subjects

Cited by 311 publications

References 17 publications

Persistence of isolated antibodies to woodchuck hepatitis virus core antigen is indicative of occult infection

Persistence of isolated antibodies to woodchuck hepatitis virus core antigen is indicative of occult infection

Frequent amplification of c-myc in ground squirrel liver tumors associated with past or ongoing infection with a hepadnavirus.

High prevalence of mutations at codon 249 of the p53 gene in hepatocellular carcinomas from Senegal

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