Type B Hepatitis after Transfusion with Blood Containing Antibody to Hepatitis B Core Antigen

Hoofnagle, Jay H.; Seeff, Leonard B.; Bales, Z B; Zimmerman, Hyman J.

doi:10.1056/nejm197806222982502

Cited by 430 publications

(199 citation statements)

References 24 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%

“…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 acute hepatitis B. 13,14 Moreover, transmission of HBV from blood and organ donors with isolated anti-HBc to virus-naïve individuals 5,[15][16][17][18][19][20][21] and reactivation of the infection in anti-HBc-positive persons 22,23 have been reported. Also, it is perceived that occult HBV infection with or without anti-HBc is associated with an increased risk of developing hepatocellular carcinoma.…”

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confidence: 89%

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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%

supporting

confidence: 89%

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

et al. 2004

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“…8,30 However, the prevalence of seronegative varied (range, 0-88%) from individual studies in HBsAg-negative patients with or without HCC. 8 Although occult HBV infection has been well documented since 1978, 32 the underlying molecular and immunologic mechanisms still require further elucidation. Several hypotheses have been proposed for the development of occult HBV infection.…”

Section: Discussionmentioning

confidence: 99%

A study on sequence variations in pre‐S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non‐B, non‐C hepatocellular carcinoma patients in Taiwan

Chen

Changchien

Lee

et al. 2009

Intl Journal of Cancer

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This study was to investigate the clinical significance and virologic factors of occult hepatitis B virus (HBV) infection in hepatocellular carcinoma (HCC) patients without hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (non-B, non-C) in Taiwan. Serum HBV DNA (occult HBV) was detected in 90 of 222 non-B, non-C HCC patients and 24 of 300 non-B, non-C controls without HCC. Of 90 occult HBV-infected HCC patients, the sequences of HBV pre-S/surface, X and enhancer II/core promoter/precore genes were analyzed from 40 patients. Direct sequencing of such genes was also performed in 24 non-B, non-C controls without HCC and 40 HBsAg-positive HCC controls. Compared with non-B, non-C controls without HCC, non-B, non-C subjects with HCC had significantly higher prevalence of occult HBV (p < 0.0001). Moreover, M1I and Q2K in pre-S2 gene and G1721A were more common in occult HBV-infected patients with HCC than in those without HCC. Compared with the HBsAg-positive HCC controls, occult HBV-infected HCC patients had higher frequencies of M1I and Q2K in pre-S2 gene, G185R and S210N in surface gene, A36T and A44L in X gene, and G1721A in enhancer II gene, and had lower rates of pre-S deletions and A1762T/G1764A, A1846T, G1896A and G1899A in core promoter/precore genes. Multivariate analysis showed Q2K in pre-S2 gene, G1721A and A1846T were independent factors for occult HBV-infected HCC. Our study suggested that the virological factors of HBV related to HCC were different between occult HBV-infected and HBsAgpositive patients. The G1721A, M1I and Q2K in pre-S2 gene may be useful viral markers for HCC in occult HBV carriers. ' UICCKey words: hepatitis B virus; occult hepatitis B virus; hepatocellular carcinoma; precore mutation; core promoter mutation Hepatitis B virus (HBV) infection is a major health problem associated with 1 million deaths annually worldwide. 1 A wide range of clinical manifestations has been established for chronic HBV infection from asymptomatic carriers to severe chronic liver disease, including those with cirrhosis and hepatocellular carcinoma (HCC). 2-4 Chronic HBV infection is characterized by persistent hepatitis B surface antigen (HBsAg) and viremia. 1,2 Early studies revealed that the clearance of HBsAg in HBV patients is associated with undetectable serum HBV DNA and disease remission. However, accumulating data indicate that a low level of HBV DNA remains detectable in serum and liver tissues in some patients cleared of HBsAg from either acute self-limited or chronic HBV infection. Occult HBV infection was detected even among family members of HBV carriers. 5 This so-called occult HBV infection has been identified by sensitive polymerase chain reaction (PCR) assays that detect low levels of HBV DNA in serum and/or liver tissue of HBsAg-negative subjects. [6][7][8] Since the early 1980s, several studies have reported the detection of HBV DNA in both tumorous and non-tumorous liver tissue of HBsAg-negative HCC patients. 9,10 However, whether occult HBV infection also contributes to the...

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“…Described many years ago, even before the fi nding of HCV (6,19) , the infection's true prevalence, physiopathogeny and clinical impact are still a matter of debate (1,2,5,7,11,23) .…”

Section: Introductionmentioning

confidence: 99%

Occult hepatitis B virus infection in patients with chronic liver disease due to hepatitis C virus and hepatocellular carcinoma in Brazil

Branco

Mattos

Coral

et al. 2007

Arq. Gastroenterol.

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-Background -The prevalence and consequences of occult HBV infection in patients with chronic liver disease by HCV remain unknown. Aims -To evaluate the prevalence of occult HBV infection in a population of HCV-infected patients with hepatocellular carcinoma. Methods -The serum samples were tested for HBV DNA by nested PCR and liver tissue analysis was carried out using the immunohistochemical technique of 66 HBsAg-negative patients: 26 patients with chronic hepatitis by HCV (group 1), 20 with hepatocellular carcinoma related to chronic infection by HCV (group 2) and 20 with negative viral markers for hepatitis B and C (control group). Results -Occult HBV infection was diagnosed in the liver tissue of 9/46 (19.5%) HCV-infected patients. Prevalence of occult B infection was evaluated in the HCV-infected patients with and without hepatocellular carcinoma, and there were seven (77.7%) of whom from group 2, conferring a 35% prevalence of this group. No serum sample was positive for HBV DNA in the three groups. Conclusion -Occult infection B is frequently detected in liver tissue of HCV-infected patients, especially in cases of hepatocellular carcinoma. However large studies are needed to confi rm that co-infection could determine a worse progress of chronic liver disease in this population.

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Type B Hepatitis after Transfusion with Blood Containing Antibody to Hepatitis B Core Antigen

Cited by 430 publications

References 24 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

A study on sequence variations in pre‐S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non‐B, non‐C hepatocellular carcinoma patients in Taiwan

Occult hepatitis B virus infection in patients with chronic liver disease due to hepatitis C virus and hepatocellular carcinoma in Brazil

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