Integration of HBV-DNA may not be a prerequisite for the maintenance of the state of malignant transformation

Fowler, Martin; Greenfield, Charlie; Chu, Chia–Ming; Karayiannis, Peter; Dunk, Arthur A.; Lok, Anna S.; Lai, Ching–Lung; Yeoh, Eng‐Kiong; Monjardino, J; Wankya, B. M.; Thomas, Howard

doi:10.1016/s0168-8278(86)80080-0

Cited by 53 publications

(28 citation statements)

References 26 publications

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“…[12][13][14] The detection of serum HBV DNA by PCR, showing almost perfect agreement (k ϭ 0.91) with replicative HBV DNA in liver tissue (authors' unpublished data), may well represent persistent HBV replication in liver. In this study, 70% (63/90) of HCC patients with chronic HBV infection had detectable serum HBV DNA by PCR.…”

Section: Discussionmentioning

confidence: 82%

Detection of serum hepatitis B, C, and D viral nucleic acids and its implications in hepatocellular carcinoma patients

Huang

Chau

et al. 1998

Journal of Gastroenterology

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The association of viremia, elevated serum alanine aminotransferase (ALT) levels, and hepatocyte inflammatory activity in hepatocellular carcinoma (HCC) patients was studied. Serum samples from 114 HCC patients undergoing surgery were assayed for hepatitis B, C, and D viral nucleic acids by polymerase chain reaction (PCR) prior to surgery. Of these patients, 65 had HBV infection alone, 15 had HCV infection alone, 4 had HDV infection, 20 had HBV and HCV superinfection, 1 had triple viral infection, and 9 were negative for HBV and HCV infections. The prevalence of active viral replication was significantly higher in HCV than in HBV (92% versus 70%; P = 0.006) patients, and significantly higher mean serum ALT levels were also noted in the HCV group than in the HBV group (P = 0.02). The incidence of marked ALT elevation (>200 U/l) was highest in the HCV (27%) and the HDV (25%) groups. Patients in the HCV group were 10 years older than those in the HBV group. Viral superinfection did not accelerate the development of HCC. Viral replication persisted in a significant portion of HCC patients and a higher prevalence of hepatic inflammation was noted in patients with HCV- and, possibly, HDV-related HCC.

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Section: Discussionmentioning

confidence: 82%

Detection of serum hepatitis B, C, and D viral nucleic acids and its implications in hepatocellular carcinoma patients

Huang

Chau

et al. 1998

Journal of Gastroenterology

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“…HBV DNA integration has been generally described in both HCC and cirrhotic patients with long-term CHB [42,46,60,61,62,63,64,65,66,67,68,69], but recently also prior to histologically observable liver damage in CHB patients [7,70]. Even earlier integration of HBV DNA has been reported in congenitally-infected children (as young as 5 months) with severe liver disease [71,72] and in patients with acute HBV infection [73].…”

Section: Hbv Dna Integrationmentioning

confidence: 99%

HBV DNA Integration: Molecular Mechanisms and Clinical Implications

Tu¹,

Budzinska²,

Shackel³

et al. 2017

Viruses

312

302

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Chronic infection with the Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality. One peculiar observation in cells infected with HBV (or with closely‑related animal hepadnaviruses) is the presence of viral DNA integration in the host cell genome, despite this form being a replicative dead-end for the virus. The frequent finding of somatic integration of viral DNA suggests an evolutionary benefit for the virus; however, the mechanism of integration, its functions, and the clinical implications remain unknown. Here we review the current body of knowledge of HBV DNA integration, with particular focus on the molecular mechanisms and its clinical implications (including the possible consequences of replication-independent antigen expression and its possible role in hepatocellular carcinoma). HBV DNA integration is likely to influence HBV replication, persistence, and pathogenesis, and so deserves greater attention in future studies.

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“…Other investigators (Hino et al, 1985;Fowler et al, 1986;Pasquinelli et al, 1986) have been unable to detect hepatic HBV-DNA in the absence of serum markers or HBV-RNA transcripts (Yokosuka et al, 1986). A similar situation occurred when using immuno-histochemistry Tur-Kaspa et al, 1986) and in situ hybridisation in combination with molecular hybridisation (Blum et al, 1983).…”

Section: Discussionmentioning

confidence: 88%

Frequency of hepatic HBV-DNA in patients with cirrhosis and hepatocellular carcinoma: relation to serum HBV markers

White

Pj²,

Davison³

et al. 1990

Br J Cancer

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al., 1978;Beasley, 1982) and in some instances integrated HBV-DNA was detected in the genome of tumour cells (Popper et al., 1987;Brechot et al., 1981Brechot et al., , 1983. Following reports that hepatic HBV-DNA could be detected in non-tumorous tissue and in chronic HBV carriers (Shafritz et al., 1981;Brechot et al., 1982), it was suggested that detection of integrated HBV-DNA might define patients at risk of developing HCC.We are currently undertaking a large prospective study of cirrhotic patients aimed at delineating risk factors such as the presence of serum markers of HBV infection, which may be associated with an increased risk of malignant change. In view of reports that hepatic HBV-DNA could occasionally be detected even in the absence of conventional serum markers (Vergani et al., 1982;Brechot et al., 1985), it became important to assess the frequency of hepatic HBV-DNA in relation to HBV serum markers. We now present our findings on hepatic HBV-DNA in a series of 156 biopsies from cirrhotic patients with various forms of long established liver disease including HCC. Material and methodsLiver biopsies were performed on 156 patients, the majority of whom were of Northern European extraction (102, 65.4%), while the remainder were from Southern Europe and other Mediterranean regions (39, 25%), Arabian and Asian subcontinent (10, 6.4%), the Far East (3, 1.9%) and Africa (2, 1.3%). One hundred and two were male and 54 female. All patients had histologically proven cirrhosis. Of the 138 subjects without HCC, 66 had chronic active hepatitis (CAH), of which 46 had HBV serum markers, 11 were of the autoimmune type (SMA/ANF > 1:80) and nine were 'idiopathic', probably due to non-A non-B infection. Seven of the latter were from the Middle East, and two were hospitalised for acute NANB hepatitis; in both cases a diagnosis of cirrhosis was made 1 year later. The remainder comprised patients with alcoholic (ALC) 26, primary biliary cirrhosis (PBC) 33, cryptogenic five, secondary biliary cirrhosis three, Wilson's disease two and one each with alpha-lantitrypsin disease, Budd-Chiari and haemochromatosis (Table I).Also investigated were 18 subjects with HCC, eight of whom had previously been diagnosed as having cirrhosis without tumour, while the other 10 presented with tumour on cirrhosis. One HCC patient had tumour as well as surrounding tissue analysed.

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Integration of HBV-DNA may not be a prerequisite for the maintenance of the state of malignant transformation

Cited by 53 publications

References 26 publications

Detection of serum hepatitis B, C, and D viral nucleic acids and its implications in hepatocellular carcinoma patients

Detection of serum hepatitis B, C, and D viral nucleic acids and its implications in hepatocellular carcinoma patients

HBV DNA Integration: Molecular Mechanisms and Clinical Implications

Frequency of hepatic HBV-DNA in patients with cirrhosis and hepatocellular carcinoma: relation to serum HBV markers

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