Variations of hepatitis B virus precore/core gene sequence in acute and fulminant hepatitis B

Aye, Thein Thein; Uchida, Tatsuo; Becker, Sven O.; Hirashima, Masanori; Shikata, Toshio; Komine, Fumihiko; Moriyama, Mitsuhiko; Arakawa, Yasuyuki; Mima, Satoaki; Mizokami, Masashi

doi:10.1007/bf02093794

Cited by 37 publications

(32 citation statements)

References 23 publications

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“…The Ser-169 frequently was changed into Pro. This mutation was described in patients with fulminant hepatitis [133].…”

Section: Mutations Of the Core-regionmentioning

confidence: 91%

“…Point mutations within the CD 4 + T-cell epitope aa 48-69 [117] were described in severe liver diseases from patients from South-East-Asia [126,127], from immunocompromized patients [132] and from hepatoma tissues [16] [133]. These mutations were found after antiHBe seroconversion in chronic active hepatitis and in immunocompromized patients.…”

Section: Mutations Of the Core-regionmentioning

confidence: 99%

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Molecular, immunological and clinical properties of mutated hepatitis B viruses

Kreutz¹

2002

J Cellular Molecular Medi

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Hepatitis B virus (HBV) is at the origin of severe liver diseases like chronic active hepatitis, liver cirrhosis and hepatocellular carcinoma. There are some groups of patients with high risk of generation of HBV mutants: infected infants, immunosupressed individuals (including hemodialysis patients), patients treated with interferon and lamivudine for chronic HBV infection. These groups are the target for molecular investigations reviewed in this paper. The emergence of lamivudine‐ or other antiviral‐resistant variants, rises concern regarding long term use of these drugs. Infection or immunization with one HBV subtype confers immunity to all subtypes. However, reinfection or reactivation of latent HBV infection with HBV mutants have been reported in patients undergoing transplant and those infected with HIV. Mutations of the viral genome which are not replicative incompetent can be selected in further course of infection or under prolonged antiviral treatment and might maintain the liver disease. Four open reading frames (ORF) which are called S‐gene, C‐gene, X‐gene and P‐gene were identified within the HBV genome. Mutations may affect each of the ORFs. Mutated S‐genes were described to be responsible for HBV‐infections in successfully vaccinated persons, mutated C‐genes were found to provoke severe chronic liver diseases, mutated X‐genes could cause serious medical problemes in blood donors by escaping the conventional test systems and mutated P‐genes were considered to be the reason for chemotherapeutic drug resistance. This paper reviews molecular, immunological and clinical aspects of the HBV mutants.

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“…The Ser-169 frequently was changed into Pro. This mutation was described in patients with fulminant hepatitis [133].…”

Section: Mutations Of the Core-regionmentioning

confidence: 91%

Section: Mutations Of the Core-regionmentioning

confidence: 99%

Molecular, immunological and clinical properties of mutated hepatitis B viruses

Kreutz¹

2002

J Cellular Molecular Medi

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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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“…Patients HBV infection and that these mutations were significantly who remained HBeAg positive and had normal aminoassociated with the appearance of precore stop codon mutatransferase levels (Group I) maintained higher serum tion (G-A, nucleotide 1896), hepatitis B e antigen (HBeAg) hepatitis B virus (HBV) DNA levels but significantly negativity, and active liver disease. [1][2][3][4][5][6][7][8] These findings suggest lower rates of both nucleotide and amino acid changes that mutations in the HBV core gene sequence may affect during follow-up compared with patients who remained immune clearance of HBV and activity of liver disease. HowHBeAg positive but had elevated aminotransferase levever, most reports were based on cross-sectional studies in els (Group II) and patients who cleared HBeAg (Group which sequences of individual patients were compared III).…”

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confidence: 99%

High Rate of Mutations in the Hepatitis B Core Gene During the Immune Clearance Phase of Chronic Hepatitis B Virus Infection

1996

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rates of changes were found during the immune clearCross-sectional studies reported that hepatitis B core ance of chronic hepatitis B infection. Interferon therapy gene mutations are associated with active liver disease did not induce a higher rate or specific pattern of mutaand responsiveness to interferon therapy. In view of the tions in the hepatitis B core gene. Response to interferon heterogeneity in published sequences, it is not possible therapy in HBeAg positive patients was unrelated to the to tell whether the differences in sequences observed number or location of hepatitis B core gene mutations. were true mutations that developed during the course (HEPATOLOGY 1996;24:32-37.) of infection. We conducted a longitudinal study to determine the rate of hepatitis B core gene mutations and the timing of these mutations in relation to hepatitis B virus Naturally occurring mutations in the hepatitis B virus replication, activity of liver disease, hepatitis B e antigen (HBV) genome have been attributed to play a role in the (HBeAg) seroconversion, and interferon therapy. Serial activity of HBV-related liver disease and in the persistence sera from 55 patients with chronic hepatitis B infection of HBV infection. were analyzed by direct sequencing of the hepatitis BWe and others have reported that mutations in the HBV precore/core gene to identify the nucleotide and amino core gene can be frequently detected in patients with chronic acid changes that emerged during follow-up. Patients HBV infection and that these mutations were significantly who remained HBeAg positive and had normal aminoassociated with the appearance of precore stop codon mutatransferase levels (Group I) maintained higher serum tion (G-A, nucleotide 1896), hepatitis B e antigen (HBeAg) hepatitis B virus (HBV) DNA levels but significantly negativity, and active liver disease. 1-8 These findings suggest lower rates of both nucleotide and amino acid changes that mutations in the HBV core gene sequence may affect during follow-up compared with patients who remained immune clearance of HBV and activity of liver disease. HowHBeAg positive but had elevated aminotransferase levever, most reports were based on cross-sectional studies in els (Group II) and patients who cleared HBeAg (Group which sequences of individual patients were compared III). The rates of nucleotide and amino acid changes in against published sequences. In view of the heterogeneity in Groups I, II, and III patients were: 0.4 { 0.1, 1.9 { 0.3, published sequences, it is not possible to tell whether the and 2.4 { 0.4/nucleotide position/year; and 0.04 { 0.02, nucleotide or amino acid differences observed were true mu-0.21 { 0.05, and 0.38 { 0.07/codon/year, respectively. Most tations that developed in the individual patients. In a recent of the amino acid changes in Groups II and III patients study comparing the HBV core gene sequences among hepatioccurred during or shortly after flares in aminotransfertis B surface antigen positive family members, we found that ase levels, before HB...

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Variations of hepatitis B virus precore/core gene sequence in acute and fulminant hepatitis B

Cited by 37 publications

References 23 publications

Molecular, immunological and clinical properties of mutated hepatitis B viruses

Molecular, immunological and clinical properties of mutated hepatitis B viruses

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

High Rate of Mutations in the Hepatitis B Core Gene During the Immune Clearance Phase of Chronic Hepatitis B Virus Infection

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