Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity
Section snippets
Patients
We studied a cohort of 151 consecutive French patients who were referred to our liver department (Hôtel-Dieu Hospital, Lyon, France) for the management of compensated chronic hepatitis B from 1994 to 1997. All patients had liver biopsy-proven chronic hepatitis B. At the time of referral, none of the patients had clinical manifestation of decompensation of the liver disease, such as jaundice, ascites, variceal bleeding, encephalopathy, or liver carcinoma. None of the patients received
Epidemiological characteristics of the patients
The 151 patients were classified into two groups according to the results of HBeAg/anti-HBe serology. Eighty-five patients were positive for HBeAg and 66 patients were positive for anti-HBe. The demographic characteristics of the patients are presented in detail in Table 1. HBeAg positive patients were younger than those who were anti-HBe positive (p<0.001). There was no statistical difference between the two groups in terms of sex ratio, but a difference was observed in terms of mode of
Discussion
In this study of a large cohort of 151 French patients with ongoing chronic hepatitis B, we found that HBV genotyping can be performed on a large scale using a new post-PCR hybridization assay. This line probe assay was previously set up for HCV genotyping (40) and was applied only very recently to HBV genome detection 33., 36.. This assay was first evaluated blindly with our in-house tests 15., 20., 31. and viral genome sequence analysis that demonstrated its reliability for the rapid
Acknowledgements
We thank Dr Franise Huisse (Chiron diagnostics, France) for providing the branched DNA assay kits. This work was supported by grants form the INSERM and the“Hospices Civils de Lyon”.
References (48)
- et al.
Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate
Cell
(1982) - et al.
Complete genomes, phylogenetic relatedness, and structural proteins of six strains of the hepatitis B virus, four of which represent two new genotypes
Virology
(1994) - et al.
Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection
Lancet
(1989) - et al.
Frequent and rapid emergence of mutated pre-C sequences in HBV from e-antigen positive carriers who seroconvert to anti-HBe during interferon treatment
Virology
(1992) - et al.
Active hepatitis B virus replication in the presence of anti-HBe is associated with viral variants containing an inactive pre-C region
Virology
(1990) - et al.
Replication capacities of natural and artificial precore stop codon mutants of hepatitis B virus: relevance of pregenome encapsidation signal
Virology
(1992) - et al.
The stem-loop structure of the cisencapsidation signal is highly conserved in naturally occurring hepatitis B virus variants
Virology
(1994) - et al.
Naturally occurring variants of hepatitis B virus
Adv Virus Res
(1999) - et al.
Chronic hepatitis in HBsAg carriers with serum HBV DNA and anti-HBe
Gastroenterology
(1986) - et al.
Comparison of anti-HBe-positive and HBe-antigen-positive chronic hepatitis B in France
J Hepatol
(1994)
Predictive value of precore hepatitis B virus mutations in spontaneous and interferon-induced hepatitis B e antigen clearance
Hepatology
Hepatitis B virus infection: precore mutants and its relation to viral genotypes and core mutations
Hepatology
Hepatitis B virus carriers without precore mutations in hepatitis B e antigen-negative stage show more severe liver damage
Hepatology
Low frequency of precore hepatitis B virus mutants in anti-hepatitis B e-positive reactivation after loss of hepatitis B e antigen in patients with chronic hepatitis B
Hepatology
Biologic properties of hepatitis B viral genomes with mutations in the precore promoter and precore open reading frame
Virology
Analysis of hepatitis B virus populations in an interferon-alpha-treated patient reveals predominant mutations in the C-gene and changing e-antigenicity
Virology
The precore sequence of hepatitis B virus is required for nuclear localization of the core protein
Hepatology
Hepatitis B virus infection
N Engl J Med
The clinical significance of molecular variation within the hepatitis B virus genome
Hepatology
Expression of the precore region of an avian hepatitis B virus is not required for viral replication
J Virol
The duck hepatitis B virus pre-C region encodes a signal sequence which is essential for synthesis and secretion of processed core proteins but not for virus formation
J Virol
The secretory core protein of human hepatitis B virus is expressed on the cell surface
J Virol
Antibodies in anti-HBe-positive patient sera bind to an HBe protein expressed on the cell surface of human hepatoma cells: implications for virus clearance
Hepatology
Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis
Proc Natl Acad Sci USA
Cited by (199)
Laboratory Diagnosis and Monitoring of Viral Hepatitis
2019, Gastroenterology Clinics of North AmericaGenotype characteristic and phylogenetic analysis of hepatitis B virus in northeast-Iran
2018, Infection, Genetics and EvolutionEpidemiology of HBV subgenotypes D
2015, Clinics and Research in Hepatology and GastroenterologyHBsAg expression of liver correlates with histological activities and viral replication in chronic hepatitis B
2014, Annals of HepatologyCitation Excerpt :–10 Hence, both intrahe-patic HBcAg and HBsAg expressions are closely linked to the natural course of infection and HBV replication. Among the phases of chronic hepatitis B, immune-clearance phase or named as HBeAg-positive chronic hepatitis B often occurred in younger population, exhibited less severe histological activities, and harbored fewer rates of precore A1896 mutation and basal core promoter (BCP) T1762/A1764 mutations than HBeAg-negative chronic hepatitis B.11–14 The course of chronic hepatitis B is dynamic that resulted from interaction of viral replication and host immune system. Consequently, diversity in clinical features or histological activities is commonly observed in HBeAg positive patients.