Posttransfusion Fulminant Hepatitis B Associated with Precore‐Defective HBV Mutants

Kojima, Mineo; Shimizu, Mai; Tsuchimochi, T.; Koyasu, Misako; Tanaka, Satoshi; Iizuka, Hisao; Tanaka, Takeshi; Okatnoto, H.; Tsuda, Fumio; Miyakawa, Yuzo; Matsui, Makoto

doi:10.1111/j.1423-0410.1991.tb00868.x

Cited by 74 publications

(19 citation statements)

References 34 publications

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“…16 17 There have been a few reports that have described a relationship between precore mutations and fulminant hepatitis (FH). [18][19][20][21][22][23] Similarly, Sato et al reported the presence of an A to T mutation at nt 1762 and a G to A mutation at nt 1764 in the core promoter region (T1762 and A1764) in Japanese patients with FH who did not manifest precore stop codon mutations. 24 However, a study of patients from the USA and Europe failed to reveal such an association.…”

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confidence: 99%

Distribution of hepatitis B viral genotypes and mutations in the core promoter and precore regions in acute forms of liver disease in patients from Chiba, Japan

Imamura

Yokosuka²,

Kurihara³

et al. 2003

Gut

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Background: Although it has been reported that different hepatitis B virus (HBV) genotypes induce different clinical characteristics in patients with chronic liver diseases (CLD), there have been few reports that have detailed the distribution of HBV genotypes in acute forms of liver disease. Methods: HBV genotypes were determined in 61 patients who had acute forms of liver disease (45 had acute self limited hepatitis (AH) and 16 had fulminant hepatitis (FH)) and in 531 patients with CLD, including 19 patients with severe acute exacerbation of CLD. We also analysed the enhancer II, core promoter, and precore region sequences for the presence of mutations. Results: Expression of genotype B in patients with acute forms of liver disease was significantly greater than in those with CLD (39.3% v 11.7%, respectively; p,0.001). Furthermore, expression of genotype B was significantly greater in patients with FH than in those with AH (62.5% v 31.1%, respectively; p = 0.027). The precore mutation A1896 and the core promoter mutation at nt 1753 and 1754 were found more frequently in FH than in AH, and genotype B was predominant in FH regardless of the presence of these mutations. Conclusions: HBV genotype B was found more frequently in patients with acute forms of liver disease than in patients with CLD, and more frequently in patients with FH than in those with AH. These results suggest that this HBV genotype may induce more severe liver damage than other viral genotypes, at least in patients from Chiba, Japan.

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confidence: 99%

Distribution of hepatitis B viral genotypes and mutations in the core promoter and precore regions in acute forms of liver disease in patients from Chiba, Japan

Imamura

Yokosuka²,

Kurihara³

et al. 2003

Gut

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“…For example, HBV variants containing a stop mutation in the precore gene are enriched during chronic infection under a variety of circumstances, and some reports have associated the transmission of such variants with a subsequent fulminant hepatitis. [5][6][7] However, the specific association of precore stop mutations with fulminant hepatitis is uncertain, [8][9][10] and the pathogenesis of such variants cannot be directly evaluated.The duck hepatitis B virus (DHBV) model has been used to examine the regulation of viral replication by the preS protein. 11 Several engineered single amino acid substitutions of DHBV preS residues 128, 131, and 133 were found to create viral envelope variants that produced elevated levels of viral cccDNA in primary hepatocyte cultures.…”

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Acute liver injury following infection with a cytopathic strain of duck hepatitis B virus

1999

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A variant avian hepadnavirus that has been shown to destroy hepatocytes in vitro was found to be cytopathic in vivo. A single amino acid change of glycine to glutamic acid at position 133 (G133E) in the preS protein of duck hepatitis B virus (DHBV) caused an increase in the intranuclear pool of viral covalently closed circular DNA (cccDNA), resulting in a transient elevation of viral replication and eventual hepatocyte destruction. In vivo viral infection with the G133E virus was compared with infection with wild-type virus over a 72-day period. Birds were inoculated with virus at day 2 post-hatch to ensure a high percentage of infected hepatocytes and potential persistence of virus. Birds infected with the G133E virus had increased periportal cellular proliferation and numerous lysed apoptotic hepatocytes following 100% infection of hepatocytes. The liver damage within G133E virus-infected birds subsided over time, resulting in mild chronic hepatitis that was similar to that observed within wild-type virusinfected birds. The subsidence of liver damage in G133E virus-infected birds coincided with a reduction of viral cccDNA to wild-type virus levels in the liver. Our study indicates that maintenance of wild-type levels of viral cccDNA promotes persistence of virus infection by establishing a noncytopathic infection. (HEPATOLOGY 1999;29:563-571.)Hepadnaviruses cause persistent productive infections of each infected hepatocyte. During the initiation of infection, the relaxed circular DNA (rcDNA) genome in the virion is converted to covalently closed circular DNA (cccDNA) in the nucleus. Viral cccDNA is used as the template for viral RNA transcription, resulting in the production of a viral RNA molecule (pregenome) that is greater than one genome in length. The RNA pregenome is encapsidated within a viral core particle, where it is reverse-transcribed by the viralencoded DNA polymerase to produce viral minus-strand DNA. 1 Plus-strand DNA synthesis is then carried out by the same viral DNA polymerase using the viral DNA minusstrand as a template. The final DNA product contained with the capsid is a double-stranded molecule that is held in a circular conformation by a short region of base-pairing between the 5Ј end of the two strands. This form of viral DNA is referred to as relaxed circular DNA, or rcDNA. The viral capsids that contain rcDNA associate with the viral envelope proteins at the endoplasmic reticulum and are secreted as virions. Alternatively, rcDNA molecules may enter into the nucleus of the infected hepatocyte, where they are converted to additional molecules of cccDNA and cause increased levels of viral replication. The production of new viral cccDNA is regulated by the viral large envelope protein (preS) by a mechanism that has not been biochemically defined. 2 Presumably, an interaction between the preS protein and rcDNAcontaining capsids is necessary for enveloped virus formation and promotes secretion of viral rcDNA from the hepatocyte as virions. Because defects in preS that specifically inhibit ...

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“…Sequencing of the HBV genome from patients with fulminant hepatitis B revealed a high percentage of precore-defective mutations in any routes of HBV transmission (22,65,66,71,93,121), although this percentage is lower in the patients in Western countries. The author's series of study revealed 12 (86%) having HBV with precore-defective mutation among 14 patients with fulminant hepatitis (3).…”

Section: Fulminant Hepatitis and Severe Hepatitismentioning

confidence: 99%

Genetic Variations of the Hepatitis B Virus and Their Clinical Relevance

Uchida

1993

Microbiology and Immunology

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Posttransfusion Fulminant Hepatitis B Associated with Precore‐Defective HBV Mutants

Cited by 74 publications

References 34 publications

Distribution of hepatitis B viral genotypes and mutations in the core promoter and precore regions in acute forms of liver disease in patients from Chiba, Japan

Distribution of hepatitis B viral genotypes and mutations in the core promoter and precore regions in acute forms of liver disease in patients from Chiba, Japan

Acute liver injury following infection with a cytopathic strain of duck hepatitis B virus

Genetic Variations of the Hepatitis B Virus and Their Clinical Relevance

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