Clinical implications of mutations in the hepatitis B virus genome

Torre, Francesco; Naoumov, N.V.

doi:10.1046/j.1365-2362.1998.00346.x

Cited by 14 publications

(12 citation statements)

References 163 publications

(165 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among them is a G-to-A change at nucleotide 1896 (codon 28), which creates a premature stop codon (precore stop codon mutant). This mutation prevents the translation of the precore protein and completely abolishes the production of HBeAg (27). In addition, nucleotide variability (T or C) at position 1858 (codon 15) is commonly observed (11).…”

Section: Discussionmentioning

confidence: 99%

Clinical and Virological Aspects of Blood Donors Infected with Hepatitis B Virus Genotypes B and C

et al. 2002

View full text Add to dashboard Cite

Pathogenic and therapeutic differences among hepatitis B virus (HBV) genotypes have been documented. However, the association of virological characteristics with clinical differences among HBV genotypes remains unclear. We therefore studied the clinical and virological characteristics of Taiwanese volunteer blood donors infected with HBV genotypes B and C. HBV genotypes were determined in 300 candidate blood donors positive for HBV surface antigen (HBsAg), and sequences of the precore gene of the HBV genome were determined in 50 HBV e antigen (HBeAg)-positive and 50 HBeAg-negative blood donors. Of 300 HBsAg-positive blood donors, 10% had elevated serum aminotransferase levels and 27% were positive for HBeAg. HBV genotype distribution in 264 viremic carriers was as follows: B, 221 (83.7%); C, 39 (14.8%); F, 1 (0.4%); and mixed infection, 3 (1.1%). Blood donors with genotype C infection tended to have a higher frequency of HBeAg positivity and a higher serum HBV DNA level than those with genotype B infection. The frequency of precore stop codon mutation was significantly higher in HBeAg-negative blood donors than HBeAg-positive ones, irrespective of HBV genotypes. Meanwhile, only 5% of blood donors with genotype C infection had C-1858 strains. In conclusion, mixed infection of HBV genotypes indeed occurs, and genotype C has a higher serum HBV DNA level than genotype B. Precore stop codon mutation is common in HBeAg-negative HBV carriers, irrespective of HBV genotypes. In contrast, precore C-1858 strains are rarely identified in Taiwanese HBV genotype C.Hepatitis B virus (HBV) infection is a global health problem, and more than 350 million people of the world population are chronic carriers of the virus (7). The infection is associated with a wide clinical spectrum, ranging from acute or fulminant hepatitis to various forms of chronic infection, including asymptomatic carrier status, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) (3, 7). Although serological and genotypic classifications of HBV have been well documented (20, 24), the clinical significance of HBV genotypes in terms of clinical outcomes and therapeutic response to antiviral therapy in patients with chronic HBV infection remained largely unknown until recently. Our previous studies indicated that HBV genotypes B and C are the most prevalent viral strains in Taiwan, and genotype C is associated with the development of cirrhosis and HCC while genotype B may be associated with the development of HCC in young patients (8). In addition, HBV genotype C is associated with a higher frequency of core promoter mutation and a lower response rate to alpha interferon therapy compared to genotype B (10). Taken together, these data suggest the possible pathogenic and therapeutic differences among HBV genotypes. However, the association of virological characteristics, including efficiency of viral replication as well as viral genome variability, with these clinical differences among HBV genotypes remains unclear. We therefore studied the clinical fe...

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical and Virological Aspects of Blood Donors Infected with Hepatitis B Virus Genotypes B and C

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Additionally, the gLCR assay can be automated (1) similar to methods used for the commercial detection of Chlamydia trachomatis (5). Other identified immune or diagnostic escape mutations, such as T/I126A/S, Q129H, K/L141E, and D144A (24,27), could also be identified by including specific probes in a gLCR mixture with the a determinant amplified product.…”

Section: Discussionmentioning

confidence: 99%

Sensitive Detection of HBsAg Mutants by a Gap Ligase Chain Reaction Assay

Osiowy

2002

J Clin Microbiol

View full text Add to dashboard Cite

Hepatitis B virus (HBV) surface gene variants have been associated with diagnostic escape and immune escape following vaccination. The most common mutation observed in these variants is a glycine-to-arginine substitution at amino acid 145 (G145R). In order to sensitively detect the presence of this mutant in serum, a new molecular detection system was developed; in this new system, a gap ligase chain reaction (gLCR) assay was coupled with electrochemiluminescence detection of reaction products. The gLCR assay could detect approximately 10 copies of mutant DNA and could discriminate low levels of mutant DNA in the presence of excess wild-type DNA. Detection of the G145R mutant in clinical specimens was evaluated by testing 56 suspect serum specimens. The G145R mutation was observed in 18 of 28 HBV-DNA-positive samples. The approximate percentage of mutant present in each specimen was calculated by comparison with a standard curve of an increasing ratio of mutant DNA to wild-type DNA. Most samples contained a very low percentage of mutant virus (approximately 5%), with an observed range of approximately 3 to 74%. The G145R mutation was most frequently observed in specimens producing a diagnostic anomaly or from transplant patients but was also observed in specimens from vaccinated individuals and specimens in which HBsAg diagnostic escape was suspected. Therefore, the gLCR assay is a sensitive and specific method for detection of G145R mutants, which could be modified to include the detection of other HBV mutants.

show abstract

“…It is, however, clear that the substitution rates within an individual vary and individuals with asymptomatic disease have very low rates of mutation (McIntosh et al, 1998), perhaps suggesting that the host immune response, which may be responsible for disease activity, leads to selection of preferred mutations (Lin et al, 2001, Preikschat et al, 1999. Taken together, these studies indicate that the outcome of infection with the hepatitis B virus is determined by complex interac-tions involving the age at infection, the viral and host genotype and the effects of the host response on viral replication (Torre and Naoumov, 1998;Gunther, 2000;Bartholomeusz and Locarnini, 2001;Kao et al, 2002;Kramvis and Kew, 2005).…”

Section: Introductionmentioning

confidence: 95%

Genome-wide characterisation of Hepatitis B mutations involved in clinical outcome

et al. 2006

View full text Add to dashboard Cite

Infection with the hepatitis B virus (HBV) leads to different disease outcomes, which can be broadly divided into three categories: acute mild infection, 'fulminant' and chronic hepatitis (long-term persistent form of the infection). The factors that influence the development of these different disease states are poorly understood and may include viral polymorphisms. To investigate this possibility, we analysed 116 published complete HBV genomes for which we knew disease outcome and had access to associated information on patients (age, sex and geographic origin). Our best statistical model correctly classified 72% of the cases and retained age and sex of the patient, as well as 29 candidate mutations. With the exception of one mutation in the X gene, all were located in the viral polymerase, suggesting this gene plays a critical role in clinical outcome. Our results highlight the importance of the genetics of HBV strains in the evolution of the disease and demonstrate that disease outcome can be predicted to a surprisingly large extent with a limited number of host and viral factors.

show abstract

Clinical implications of mutations in the hepatitis B virus genome

Cited by 14 publications

References 163 publications

Clinical and Virological Aspects of Blood Donors Infected with Hepatitis B Virus Genotypes B and C

Clinical and Virological Aspects of Blood Donors Infected with Hepatitis B Virus Genotypes B and C

Sensitive Detection of HBsAg Mutants by a Gap Ligase Chain Reaction Assay

Genome-wide characterisation of Hepatitis B mutations involved in clinical outcome

Contact Info

Product

Resources

About