Different hepatitis b virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversion

Chan, H.L.Y.; Hussain, Munira; Lok, Anna S.

doi:10.1002/hep.510290352

Cited by 242 publications

(206 citation statements)

References 32 publications

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“…[29][30][31][32] Despite the fact that HBV genotypes were identified in 1988, 14 more than 10 years earlier than HCV genotypes, there are only several reports on small numbers of patients focusing on the relationship between HBV genotypes and the HBeAg/anti-HBe status with reference to mutations in PreC and BCP sequences. 18,24,25,33,34 Furthermore, none of them are case-control studies. Because the HBeAg/anti-HBe status depends heavily on sex and age of the patients, 2 a case-control study would be indispensable for sorting out the relevance of HBV genotypes with HBeAg/antiHBe as well as mutations influencing the synthesis of HbeAg.…”

Section: Discussionmentioning

confidence: 99%

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A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C

et al. 2001

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Clinical and molecular virological differences were evaluated in 50 Japanese patients chronically infected with HBV of genotype B and C who were matched for age and sex as well as the severity of liver disease in a case-control study. Hepatitis B e antigen (HBeAg) was significantly less frequent (16% vs. 42%, P < .01), whereas antibody to HBeAg (anti-HBe) was significantly more common (84% vs. 56%, P < .01) in genotype B than C patients. The predominance of mutants with G-to-A mutation at nucleotide (nt) 1896 in the precore region (A1896) over the wild-type was comparable between genotype B and C patients (60% and 62%, respectively), and it correlated with anti-HBe. The double mutation in the basic core promoter (A-to-T at nt 1762 and G-to-A at nt 1764), however, was significantly more frequent in genotype C than B patients (58% vs. 16%, P < .01), and it did not correlate with anti-HBe or HBeAg. By the multiple logistic regression analysis, the double mutation in the basic core promoter (T1762/A1764) was significantly associated with genotype C [odds ratio (OR), 9.3; 95% confidence interval (

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Section: Discussionmentioning

confidence: 99%

“…[21][22][23][24][25][26] We have conducted a case-control study to see differences in clinical features and virological characteristics, with special reference to PreC and BCP mutations, between 50 Japanese patients who were infected with HBV of genotype B and C.…”

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confidence: 99%

A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C

et al. 2001

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“…The impact of HBV genotypes on the clinical outcomes of chronic HBV infection and the response to antiviral therapy have been partially clarified (Chan et al 1999). Wai et al (2002) had studied HBV genotypes on the response to interferonalpha in 66 Chinese Han patients with HBeAgpositive chronic hepatitis.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus Genotype-Associated Variability in Antiviral Response to Adefovir Dipivoxil Therapy in Chinese Han Population

Zeng

Deng

Yang

et al. 2008

Tohoku J. Exp. Med.

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It is well known that different genotypes of hepatitis B virus (HBV) have a different sensitivity to interferon-α or lamivudine (nucleoside analogue) antiviral therapy. However, for adefovir dipivoxil (ADV, a nucleotide analogue), the antiviral response of the different genotypes remains to be clarified. In order to evaluate the response of HBV genotypes to ADV therapy and to identify factors that might affect initial virological response, we performed a retrospective analysis on patients with chronic hepatitis B (CHB) in Chinese Han population. The study included 183 patients, who had been tested positive for hepatitis B e antigen (HBeAg) and had been treated with ADV (10 mg/day) for 48 weeks. The numbers of patients infected with HBV genotype B and genotype C were 98 and 75 cases, respectively, and the remaining 10 patients were mixture infection of genotypes B plus C or genotypes B plus D. The mean HBV-DNA reduction and HBV-DNA seroclearance of genotypes B and C at 48 weeks were 3.6 log 10 and 3.1log 10 copies/ml (p < 0.05) and 41.8% and 34.6% (p < 0.05), respectively. There were no statistically significant differences between genotypes B and C in terms of HBeAg loss, anti-HBe seroconversion and normalization of serum alanine aminotransferase (ALT). Multivariate analysis showed that young age, low pretreatment HBV-DNA and/or elevated ALT level might be independent predictive factors associated with initial virological response. Thus, in Han CHB patients who are HBeAg-positive, HBV genotype B shows a better virological response to ADV therapy than does genotype C.hepatitis B virus; genotype; initial virological response; adefovir dipivoxil; chronic hepatitis B.Tohoku

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“…37 In Asian countries, where both A and non-A genotypes exist, in addition to precore mutants, BCP mutants are found. 38 For example in a recent study from China, 38% of the HBeAg-negative patients harbored the precore stop codon, 42% possessed the double BCP mutation and 12% had both mutations. 38 Similar results have been observed in other countries of the same region.…”

Section: Prevalencementioning

confidence: 99%

“…38 For example in a recent study from China, 38% of the HBeAg-negative patients harbored the precore stop codon, 42% possessed the double BCP mutation and 12% had both mutations. 38 Similar results have been observed in other countries of the same region. 39 The great majority of HBsAg (ϩ)/HBeAg (Ϫ) individuals have normal ALT values.…”

Section: Prevalencementioning

confidence: 99%

Hepatitis B e antigen–negative chronic hepatitis B

2001

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Thirty years ago, the diagnosis of chronic hepatitis B (CHB) was thought to require the presence of hepatitis B e antigen (HBeAg), as a reliable and sensitive marker of hepatitis B virus (HBV) replication. 1 Individuals positive for hepatitis B surface antigen (HBsAg) but negative for HBeAg were considered to have nonreplicative HBV infection, and if their liver enzymes were normal or nearly normal they were referred to as asymptomatic or healthy HBsAg or HBV carriers. 2 If, on the other hand, they displayed elevated serum aminotransferases and liver histology indicative of chronic hepatitis, they were generally thought to be suffering from other superimposed or complicating conditions such as hepatitis D virus infection, alcohol-induced, metabolic, autoimmune, drug-induced, or other forms of chronic liver disease. 3 In the early 1980s it became apparent that HBV could replicate in the absence of HBeAg. [4][5][6] Patients from the Mediterranean area, although negative for HBeAg and positive for antibodies to HBeAg (anti-HBe), were reported to have CHB with replicating HBV. 7 The term anti-HBe-positive or HBeAgnegative CHB was then proposed 4 and subsequently became widely accepted. In 1989 the molecular basis of this form of CHB was discovered 8,9 with the identification of HBV mutations preventing HBeAg formation from an otherwise normally replicating HBV. 10,11 With time, it became apparent that HBeAg-negative CHB, initially viewed as an atypical and rare form of CHB mainly restricted in the Mediterranean area, had a much wider geographical distribution and that its frequency was increasing. 12 Its molecular virology and immunology were found to be more complex than initially thought, 13 whereas the selection of precore HBV mutants was shown to be largely determined by the HBV genotype. 14 Mutations abolishing or diminishing HBeAg formation were identified along with changes in other parts of the HBV genome. 14 More recently, the new nucleoside analog, lamivudine, has been used to treat a sizeable number of patients with HBeAg-negative CHB, and important information on its efficacy and the development of resistance has been collected. [15][16][17][18] DEFINITION AND NOMENCLATUREThe term HBeAg-negative CHB defines the condition as disease caused by strains of HBV that are not producing HBeAg. 12 It does not specify the mutations responsible for the lack of HBeAg, i.e., a precore stop-codon mutation, 10 a double basic core promoter (BCP) mutation, or other, 14 and it says nothing about the level of HBV replication. The alternative term "precore mutant CHB," used by some investigators, also does not specify the nature of the precore mutation. In clinical practice, the term HBeAg-negative CHB is appropriate for patients with chronic HBV infection who test negative for HBeAg, are usually positive for anti-HBe, have increased alanine aminotransferase (ALT) levels and display detectable HBV DNA in serum by classical hybridization techniques. 12 Despite the fact that the identification of the underlying mutations in ...

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Different hepatitis b virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversion

Cited by 242 publications

References 32 publications

A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C

A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C

Hepatitis B Virus Genotype-Associated Variability in Antiviral Response to Adefovir Dipivoxil Therapy in Chinese Han Population

Hepatitis B e antigen–negative chronic hepatitis B

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