In situ detection of mutated hepatitis B virus in microdissected, formalinfixed liver tissues from patients with chronic hepatitis B

Background/Aims: Hepatitis B virus (HBV) quasispecies have been detected in patients with chronic hepatitis B. In order to elucidate the relationship between HBV mutation and liver cell necrosis in situ, we analyzed sublobule-sized specimens microdissected from formalin-fixed paraffin-embedded liver...

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Bibliographic Details
Published in:Journal of hepatology Vol. 30; no. 3; pp. 359 - 365
Main Authors: Kojima, Naohiko, Horiike, Norio, Michitaka, Kojiro, Onji, Morikazu
Format: Journal Article
Language:English
Published: Elsevier B.V 01.03.1999
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ISSN:0168-8278, 1600-0641
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Summary:Background/Aims: Hepatitis B virus (HBV) quasispecies have been detected in patients with chronic hepatitis B. In order to elucidate the relationship between HBV mutation and liver cell necrosis in situ, we analyzed sublobule-sized specimens microdissected from formalin-fixed paraffin-embedded liver biopsy tissues taken from patients with chronic hepatitis B. Methods: The subjects were 20 patients with chronic hepatitis B. We extracted HBV-DNA from two sublobular regions of HBV-infected liver biopsy tissue, those with the most severe and the mildest hepatitis activity, demonstrated microscopically. The DNA coding sequence of the precore-core region of HBV was determined by amplifying the DNA by the polymerase chain reaction, followed by direct sequencing. Results: In all seven patients with minimal to mild hepatitis activity, but only 4 of 13 with moderate to severe activity, the amino acid sequence of the precore-core region of HBV obtained from the region with the most severe hepatitis activity showed over 99% homology with the corresponding sequence of HBV obtained from region with the mildest hepatitis activity ( p<0.05). Conclusion: The differences between intrahepatic HBVs observed in patients with highly active hepatitis suggest that exacerbation of hepatitis in vivo is related to the appearance of variants in the precore-core region of HBV.
ISSN:0168-8278
1600-0641
DOI:10.1016/S0168-8278(99)80091-9