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Core Promoter Mutations (core + promoter_mutation)
Selected AbstractsThe natural history of chronic hepatitis BJOURNAL OF VIRAL HEPATITIS, Issue 2007C.-L. Lai Summary., The natural history of chronic hepatitis B is dependent on the age of acquiring the hepatitis B infection. Those who are infected at adolescence or adulthood (including most of the Caucasians) tend to have stable disease after hepatitis B e antigen seroconversion with normal serum alanine aminotransaminase (ALT) and hepatitis B virus (HBV) DNA levels <105 copies/mL (20 000 IU/mL). In contrast, those who are infected at birth or early childhood (including the majority of the world's hepatitis B carriers, i.e. Asians) have a prolonged immune tolerance phase followed by a prolonged immune clearance phase. A proportion of these patients have progressive disease after HBeAg seroconversion with HBV DNA <104 copies/mL (<2000 IU/mL) and ALT between 0.5 and 2× upper limit of normal. Core promoter mutations may play a part in the development of cirrhosis-related complications. However, continuing viral replication, even at a relatively low level of <104 copies/mL (<2000 IU/mL), is probably the most important factor for the development of complications. [source] Nuclear HBcAg and histology activity index as independent predictors of the expression of singly spliced HBV-RNAJOURNAL OF VIRAL HEPATITIS, Issue 1 2007I.-S. Sheen Summary., Although hepatitis B virus (HBV) RNA splicing has been reported by many researchers, the clinical significance of this event remains illusive. The present study was designed to investigate the clinical roles of singly spliced HBV-RNA. Liver biopsy tissues obtained from 32 consecutive patients were subjected to reverse transcriptase-polymerase chain reaction for the detection of singly spliced and unspliced HBV-RNA. Stepwise linear regression model was used to estimate the ratio of singly spliced to unspliced (S/US) HBV-RNA in the presence of the following variables: age, gender, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alpha-foetoprotein, status of HBV e antigen (HBeAg), status of antibody to HBeAg, HBV-DNA, histology activity index (HAI), fibrotic score, grade of cytoplasmic HBV core antigen (HBcAg), grade of nuclear HBcAg, genotype, status of precore-stop-mutation, basal core promoter mutation, previous lamivudine therapy and superinfection by other hepatitis viruses. The results showed that HAI (, = ,0.2616; P = 0.011) and grade of nuclear HBcAg expression (, = 0.5599; P =0.0067) were two independent predictors for the expression of singly spliced HBV-RNA. Further categorical analysis showed that patients with HAI score ,6 and grading of nuclear HBcAg ,2 have significantly higher S/US ratios. In conclusion, nuclear HBcAg and HAI are two independent predictors for the expression of singly spliced HBV-RNA. [source] Evolution of hepatitis B virus precore/basal core promoter gene in HBeAg-positive chronic hepatitis B patients receiving lamivudine therapyLIVER INTERNATIONAL, Issue 1 2004Chih-Lin Lin Abstract: Aim: Lamivudine is effective in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, but the relapse rate after cessation of treatment is high. The evolution of viral genome may contribute to the viral replication under antiviral pressure of lamivudine. We therefore determined the evolution of hepatitis B virus (HBV) precore/basal core promoter and polymerase genes in HBeAg-positive chronic hepatitis B patient during lamivudine therapy. Method: Thirteen patients with HBeAg-positive chronic hepatitis who had received short-term lamivudine therapy (mean, 30 weeks) during 1999,2001 were enrolled. The precore/basal core promoter region and polymerase gene were amplified and directly sequenced before, during and post lamivudine treatment. Result: HBeAg loss or seroconversion occurred in 11, but eight relapsed after stopping therapy and five had reversion of HBeAg. Before treatment, basal core promoter mutation was found in 1. In the first 3 months of therapy, a rapid decline of serum HBV DNA level accompanied with basal core promoter mutation appeared in 11 of 13 patients (vs. before therapy; P=0.003). However, this mutant was replaced by wild-type virus in four of eight patients who relapsed after treatment. There was no significant change of precore sequences before and during therapy. Conclusions: Lamivudine therapy may result in the rapid development of basal core promoter mutation of HBV, but this mutation may revert to wild type gradually after cessation of therapy. [source] Molecular evolutionary analysis and mutational pattern of full-length genomes of hepatitis B virus isolated from Belgian patients with different clinical manifestationsJOURNAL OF MEDICAL VIROLOGY, Issue 3 2010Mahmoud Reza Pourkarim Abstract Molecular evolutionary patterns of 62 HBV full-length genomes obtained from Belgian patients were characterized. Phylogenetic analysis revealed diverse HBV subgenotypes including A2 and A6 (46.8%), D1,D4 (38.8%), E (9.7%), C1 (1.6%), and B2 (1.6%). The study population consisted of patients with different ethnic origin (Caucasian, Turkish, Asian, Arab, and African). One HBV D/C recombinant isolate was identified, which encoded subtype adw2. An HBV subgenotype D4 with an aberrant subtype ayw4 was detected. Although none of the genotypes was associated with a specific disease outcome, several nucleotide substitutions, deletions and insertions were observed within the HBV preS1/S and X genes, particularly among patients with active chronic hepatitis B infection and patients with cirrhosis. Within the immunological domain of the HBsAg gene, the most frequent substitutions were sT125M and sT118A. High rates of precore and basal core promoter mutations were detected in patients infected with genotype D of HBV. Almost half of the patients who received lamivudine therapy for at least 1 year had HBV variants associated with lamivudine drug resistance. In conclusion, the most common HBV genotypes in West Europe (A and D) also prevail in Belgium. The highest degree of genetic diversity was detected in HBV genotype D. In addition, this study reveals the circulation of exotic HBV genotypes B, C, and E in Belgium. J. Med. Virol. 82:379,389, 2010. © 2010 Wiley-Liss, Inc. [source] Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearanceJOURNAL OF MEDICAL VIROLOGY, Issue 8 2007Jinlin Hou Abstract The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon-alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO-LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16-weeks interferon-alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P,=,0.014), or genotype D alone (P,=,0.05). The HBV genome analysis revealed that: (i) after 16-weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P,<,0.001) only in genotype A; (ii) the core gene of genotype A has the lowest number of amino acid variations in comparison with genotypes B, C, or D. Logistic regression analysis identified genotype A as a positive predictor of short (16 weeks) treatment response (P,=,0.001; odds ratio 6.19, 95 confidence interval 1.94,19.8), having a greater impact than baseline HBV DNA or alanine aminotransferase (ALT) levels. In contrast, the response to prolonged interferon-alpha treatment was not different between HBV genotypes. These results suggest that HBV genotype A responds earlier to interferon treatment than other genotypes, which is associated with its molecular characteristics. The optimal duration of interferon-based therapies in chronic hepatitis B may vary between different HBV genotypes. J. Med. Virol. 79: 1055,1063, 2007. © 2007 Wiley-Liss, Inc. [source] Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapyJOURNAL OF MEDICAL VIROLOGY, Issue 1 2004Reiichiro Kuwahara Abstract It has been reported that spontaneous or interferon (IFN)-induced hepatitis B e (HBe) seroconversion has usually been associated with the development of a stop codon in the precore region. However, the difference between lamivudine-induced seroconversion and spontaneous or IFN-induced seroconversion is not known. The aim of this study was to investigate the correlation between the evolution of the precore and core promoter mutations and lamivudine-induced seroconversion. Forty-five patients with chronic hepatitis B virus (HBV) infection who were treated with lamivudine for more than 1 year were enrolled. The nucleotide sequence of the precore and core promoter region was determined before and after treatment with lamivudine for 1 year. Among 29 patients who were hepatitis B e antigen (HBeAg)-positive before treatment, 12 (41.3%) lost HBeAg during the course of treatment for 1 year. Of these, eight patients (66.7%) still had precore wild type HBV after 1 year. After 1 year, reversion to precore wild type HBV was detected in 11 (64.7%) of 17 patients who had precore mutant HBV before treatment. Twelve (70.6%) of 17 patients who were persistently HBeAg-positive had precore wild type HBV before and after treatment for 1 year. Despite the loss of HBeAg, two thirds of the patients still had precore wild type HBV after the 1-year treatment. It is suggested that lamivudine-induced seroconversion differs from spontaneous or IFN-induced seroconversion in the change of nucleotides in the precore region. The reversion in the precore region may be caused by the difference of drug-susceptibility to lamivudine. The antiviral effect of lamivudine may be more effective in the precore mutant HBV than in the precore wild type HBV. J. Med. Virol. 72:26,34, 2004. © 2004 Wiley-Liss, Inc. [source] Performance of sequence analysis, INNO-LiPA line probe assays and AFFIGENE assays in the detection of hepatitis B virus polymerase and precore/core promoter mutationsJOURNAL OF VIRAL HEPATITIS, Issue 6 2006A. Olivero Summary., In this study, we compare results obtained by sequences analysis and commercial kits in the detection of hepatitis B virus (HBV) polymerase and precore (PC) and core promoter mutations. A total of 23 serum samples from lamivudine treated patients were tested for polymerase mutations by direct sequencing, INNO-LiPA HBV DR and AFFIGENE HBV DE/3TC. Full concordance among the three assays was observed in 63% of the total analysed codons. Concordant results were obtained between sequencing and LiPA in 80%, between sequencing and AFFIGENE in 73% and between LiPA and AFFIGENE in 74% of all tested codons. All discrepancies were observed in mixed population samples in which AFFIGENE and LiPA detected additional viral variants not revealed by sequence. In two patients, with serial samples, LiPA detected earlier than sequence and AFFIGENE an emerging mutate strain. PC and core promoter viral variants were detected in 28 serum samples collected from 14 HBV inactive carriers and from 14 hepatitis B patients with chronic liver disease. Direct sequencing, INNO-LiPA HBV PreCore and AFFIGENE HBV MUTANT VL 19 showed fully coincident results in 88% of tested positions. These findings showed that all assays evaluated were sensitive and accurate tools to analyse HBV genomic variability. Sequence analysis is essential to study new emerging mutations as LiPA and AFFIGENE assays are more easily useful in clinical laboratories to detect the appearance of well-characterized HBV variants. [source] Impact of determination of hepatitis B virus subgenotype and pre-core/core-promoter mutation for the prediction of acute exacerbation of asymptomatic carriersHEPATOLOGY RESEARCH, Issue 4 2009Tadashi Ikegami Aim:, A large cohort study in Japan revealed that the specific viral profile may influence the fulminant outcome in acute hepatitis B virus (HBV) infections, while the genetic influence on outcome has not been clarified in patients with acute exacerbation of chronic liver disease caused by HBV. We experienced a case of fatal liver failure that developed as the result of chronic HBV infection. To determine possible genetic factor involving acute exacerbation, genetic analysis of serum from the patient and his siblings was performed. Methods:, HBV subgenotype as well as pre-core/core-promoter mutations of samples mentioned above were determined. Results:, Patient had HBV-Bj with pre-core (1896/1899) and core-promoter (1762/1764) mutations, the genomic profile frequently seen in fulminant hepatitis caused by acute HBV infection. Conclusion:, This result suggests that determination of the HBV subgenotype and pre-core/core promoter mutations could provide a rationale for development of a treatment strategy in asymptomatic HBV carriers. [source] Differences of YMDD mutational patterns, precore/core promoter mutations, serum HBV DNA levels in lamivudine-resistant hepatitis B genotypes B and CJOURNAL OF VIRAL HEPATITIS, Issue 11 2007X. P. Pan Summary., The aims of this study were to investigate the viral differences among lamivudine-resistant hepatitis B virus (HBV) genotypes B and C in vivo. Fifty-three patients carrying lamivudine-resistant HBV were enrolled in this study. HBV genotypes, Levels of alanine aminotransferase (ALT), HBV DNA levels were monitored during therapy. The polymerase and precore/core promoter genes were amplified by polymerase chain reaction and their products were sequenced directly. Among 53 patients resistant HBV genotypes B and C accounted for 41.50% and 58.50%, respectively. The occurrence of reverse transcriptase rt204I mutants was lower in genotype B (36.36%) than that in genotype C (87.10%), whereas rt204V mutants was higher in genotype B (63.64%) than that in genotype C (12.90%). The occurrence of precore mutation (nt1896A) was higher in genotype B (77.27%) than that in genotype C (32.26%). Serum HBV DNA levels after emergence of lamivudine resistance were higher in genotype C (7.71 ± 0.80 Log copies/mL) compared with genotype B (6.97 ± 0.77 Log copies/mL). Multivariate analysis identified pretreatment HBV DNA levels, HBeAg status and HBV genotype as independent factors associated with a shorter time to lamivudine resistance(P = 0.035, P = 0.006 and P = 0.001, respectively). Multivariate analysis showed that HBV genotype (P = 0.004) and pretreatment ALT levels (P = 0.01) was independently associated with YMDD mutational patterns. The results showed that the YMDD mutational patterns, precore mutation and serum HBV DNA levels differ between lamivudine-resistant HBV genotypes B and C in vivo. It is valuable for treatment of lamivudine-resistant HBV in clinic. [source] Performance of sequence analysis, INNO-LiPA line probe assays and AFFIGENE assays in the detection of hepatitis B virus polymerase and precore/core promoter mutationsJOURNAL OF VIRAL HEPATITIS, Issue 6 2006A. Olivero Summary., In this study, we compare results obtained by sequences analysis and commercial kits in the detection of hepatitis B virus (HBV) polymerase and precore (PC) and core promoter mutations. A total of 23 serum samples from lamivudine treated patients were tested for polymerase mutations by direct sequencing, INNO-LiPA HBV DR and AFFIGENE HBV DE/3TC. Full concordance among the three assays was observed in 63% of the total analysed codons. Concordant results were obtained between sequencing and LiPA in 80%, between sequencing and AFFIGENE in 73% and between LiPA and AFFIGENE in 74% of all tested codons. All discrepancies were observed in mixed population samples in which AFFIGENE and LiPA detected additional viral variants not revealed by sequence. In two patients, with serial samples, LiPA detected earlier than sequence and AFFIGENE an emerging mutate strain. PC and core promoter viral variants were detected in 28 serum samples collected from 14 HBV inactive carriers and from 14 hepatitis B patients with chronic liver disease. Direct sequencing, INNO-LiPA HBV PreCore and AFFIGENE HBV MUTANT VL 19 showed fully coincident results in 88% of tested positions. These findings showed that all assays evaluated were sensitive and accurate tools to analyse HBV genomic variability. Sequence analysis is essential to study new emerging mutations as LiPA and AFFIGENE assays are more easily useful in clinical laboratories to detect the appearance of well-characterized HBV variants. [source] | ||||||||||