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Hepatitis B Virus Genomes of Patients With Fulminant Hepatitis Do Not Share
a Specific Mutation
MARTINA STERNECK, 1, 2 STEPHAN GÜNTHER, 2 TERESA SANTANTONIO, 3 LUTZ FISCHER, 4
CHRISTOPH E. BROELSCH, 4 HEINER GRETEN, 1 AND HANS WILL 2
The pathogenesis of fulminant Hepatitis B virus (HBV) infection is not well
understood. The aim of this study was to investigate whether there is an association
between specific viral variants and a fulminant disease course. The entire HBV
genomes from the serum of eight patients with fulminant HBV infection and one
patient with fulminant hepatitis during reinfection after liver transplantation
were investigated. After isolation and amplification of viral DNA by polymerase
chain reaction (PCR), plus and minus strands were directly sequenced. Sequence
data were analyzed by comparative sequence alignments with 35 and 2 complete
HBV genome sequences from patients without and with fulminant hepatitis, respectively.
Several point mutations were present in all regions of the genomes. Many nucleotide
changes had never or rarely been found in the reported HBV isolates from patients
without fulminant hepatitis. A distinct mutation present in all genomes was
not identified. Clusters of rare and unique mutations were observed in the enhancer
II core promoter region. Mutations previously suggested to be associated with
fulminant HBV infection were not consistently found. A precore stop codon mutation
at nucleotide position 1896 or an A-to-T mutation at nucleotide position 1762
and a G-to-A mutation at nucleotide position 1764 in the core promoter region
were present in four and three cases, respectively. Fulminant HBV infection
does not appear to be caused by a specific genomic mutation. However, various
mutations clustering in the enhancer II core promoter region may contribute
to a fulminant disease course.
Address reprint requests to: Martina Sterneck, M.D., Universitätskrankenhaus
Eppendorf, Medizinische Kernklinik und Poliklinik, Martinistr. 52, 20246 Hamburg,
Germany.
Copyright © 1996 by the American Association for the Study of Liver Diseases.
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