Epidemiological and Virological Characteristics of 2 Subgroups of Hepatitis B Virus Genotype C
15 Jun 2005-The Journal of Infectious Diseases (Oxford University Press)-Vol. 191, Iss: 12, pp 2022-2032
TL;DR: HBV genotypes C can be differentiated into 2 subgroups--namely, genotype Ce and genotype Cs--that have different epidemiological distributions and virological characteristics.
Abstract: BACKGROUND: We aimed to investigate the characteristics of hepatitis B virus (HBV) genotype C subgroups in Hong Kong and their relationship with HBV genotype C in other parts of Asia. METHODS: Full-genome nucleotide sequences of 49 HBV genotype C isolates from Chinese patients with chronic hepatitis B were compared with the sequences of 69 HBV genotype C isolates and 12 non-genotype C isolates in the GenBank database. Phylogenetic analysis was performed to define the subgroups of HBV genotype C on the basis of >4% heterogeneity of the entire HBV genome. RESULTS: HBV in 80% of patients in Hong Kong belonged to a subgroup predominantly found in Southeast Asia (Vietnam, Thailand, Myanmar, and southern China) designated as HBV genotype "Cs," and HBV in the remaining 20% of patients belonged to another subgroup, predominantly found in the Far East (Korea, Japan, and northern China), designated as HBV genotype "Ce." Overall, the mean+/-SD nucleotide sequence difference between HBV genotype Cs and HBV genotype Ce was 4.2%+/-0.3%. When HBV genotype Cs and HBV genotype Ce were compared among patients in Hong Kong, HBV genotype Cs was associated with a higher tendency to develop basal core promoter mutations (80% vs. 50%; P=.14), a higher prevalence of C at nucleotide 1858 (95% vs. 0%; P<.001), and a lower prevalence of precore stop codon mutations (5% vs. 50%; P=.002). CONCLUSIONS: HBV genotype C can be differentiated into 2 subgroups--namely, genotype Ce and genotype Cs--that have different epidemiological distributions and virological characteristics.
Citations
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TL;DR: Current knowledge of the epidemiology of genetic variability in hepadnaviruses is summarized and, due to rapid progress in the field, updates several recent reviews on HBV genotypes and subgenotypes.
Abstract: Hepatitis B virus (HBV) is a member of the hepadnavirus family. Hepadnaviruses can be found in both mammals (orthohepadnaviruses) and birds (avihepadnaviruses). The genetic variability of HBV is very high. There are eight genotypes of HBV and three clades of HBV isolates from apes that appear to be additional genotypes of HBV. Most genotypes are now divided into subgenotypes with distinct virological and epidemiological properties. In addition, recombination among HBV genotypes increases the variability of HBV. This review summarises current knowledge of the epidemiology of genetic variability in hepadnaviruses and, due to rapid progress in the field, updates several recent reviews on HBV genotypes and subgenotypes.
343 citations
TL;DR: This data indicates that vaccination against chronic hepatitis B infection leads to development of hepatocellular carcinoma, but the effects of treatment in preventing HCC are not clear.
Abstract: Summary
Background Chronic hepatitis B (CHB) infection leads to development of hepatocellular carcinoma (HCC), but the effects of treatment in preventing HCC are not clear.
Aim To study the effects of interferon (IFN) or nucleoside/tide analogue (NA) on the risk of developing HCC in CHB patients.
Methods Randomized trials, case–control and cohort studies were retrieved from five electronic databases and international conferences over the past 10 years. Relative risks (RRs) of HCC with or without treatment were studied.
Results Twelve studies (n = 2742) enrolling patients treated by IFN vs. control showed that the risk of HCC after treatment was reduced by 34% (RR: 0.66, 95% CI: 0.48–0.89). Benefit is more significant among patients with early cirrhosis than among those without cirrhosis. Five studies (n = 2289) compared patients treated by NA with control. The risk of HCC after treatment was reduced by 78% (RR: 0.22, 95% CI: 0.10–0.50). HBeAg-positive patients showed more significantly reduced HCC risk with treatment. Patients without cirrhosis benefited more from NA than those with cirrhosis. Resistance to NA has obviated the benefit of the treatment.
Conclusions IFN or NA treatment significantly reduces risk of HCC. While IFN benefited patients with cirrhosis, NA benefited patients with no cirrhosis and HBeAg-positive CHB infection.
337 citations
TL;DR: An overview of the HBV life cycle is provided, followed by review of HBV genotypes and mutants in terms of their biological properties and clinical significance.
300 citations
Cites background from "Epidemiological and Virological Cha..."
...Indeed, such mutations are more prevalent in genotype A than genotype D [87,88] and in subgenotype C1 than C2 [89–91]....
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TL;DR: High HBV DNA level and HBV genotype C, particularly subgenotype Ce, increased the risk of HCC in chronic hepatitis B.
Abstract: Purpose We aimed to investigate the impact of hepatitis B virus (HBV) DNA and HBV genotypes/subgenotypes on the risk of hepatocellular carcinoma (HCC) Patients and Methods A prospective cohort of patients infected with chronic HBV in a surveillance program for HCC since 1997 was studied Ultrasound and alpha-fetoprotein evaluation were regularly performed to detect HCC Risk factors for HCC and the relationship between HBV DNA and HBV genotypes were determined Results Among 1,006 patients with a median follow-up of 77 years, 86 patients (85%) developed HCC With reference to the low HBV DNA stratum (log HBV DNA ≤ 45 copies/mL), the hazard ratio for HCC of the intermediate HBV DNA stratum (log HBV DNA > 45 to 65 copies/mL) was 162 (95% CI, 105 to 248; P = 027) and that of the high HBV DNA stratum (log HBV DNA > 65 copies/mL) was 273 (95% CI, 176 to 425; P < 001) Among patients with genotyping results, 330 patients had HBV genotype B and 439 patients had HBV genotype C (94 subgenotype Ce an
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TL;DR: This review summarises the recent publications on the geographical distribution of genetic variants of HBV, and proposes updated criteria for the identification of new genotypes and subgenotypes of the virus.
211 citations
References
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TL;DR: The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved and modifications are incorporated into a new program, CLUSTAL W, which is freely available.
Abstract: The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.
63,427 citations
"Epidemiological and Virological Cha..." refers methods in this paper
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TL;DR: The neighbor-joining method and Sattath and Tversky's method are shown to be generally better than the other methods for reconstructing phylogenetic trees from evolutionary distance data.
Abstract: A new method called the neighbor-joining method is proposed for reconstructing phylogenetic trees from evolutionary distance data. The principle of this method is to find pairs of operational taxonomic units (OTUs [= neighbors]) that minimize the total branch length at each stage of clustering of OTUs starting with a starlike tree. The branch lengths as well as the topology of a parsimonious tree can quickly be obtained by using this method. Using computer simulation, we studied the efficiency of this method in obtaining the correct unrooted tree in comparison with that of five other tree-making methods: the unweighted pair group method of analysis, Farris's method, Sattath and Tversky's method, Li's method, and Tateno et al.'s modified Farris method. The new, neighbor-joining method and Sattath and Tversky's method are shown to be generally better than the other methods.
57,055 citations
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TL;DR: Some examples were worked out using reported globin sequences to show that synonymous substitutions occur at much higher rates than amino acid-altering substitutions in evolution.
Abstract: Some simple formulae were obtained which enable us to estimate evolutionary distances in terms of the number of nucleotide substitutions (and, also, the evolutionary rates when the divergence times are known). In comparing a pair of nucleotide sequences, we distinguish two types of differences; if homologous sites are occupied by different nucleotide bases but both are purines or both pyrimidines, the difference is called type I (or “transition” type), while, if one of the two is a purine and the other is a pyrimidine, the difference is called type II (or “transversion” type). Letting P and Q be respectively the fractions of nucleotide sites showing type I and type II differences between two sequences compared, then the evolutionary distance per site is K = — (1/2) ln {(1 — 2P — Q) }. The evolutionary rate per year is then given by k = K/(2T), where T is the time since the divergence of the two sequences. If only the third codon positions are compared, the synonymous component of the evolutionary base substitutions per site is estimated by K'S = — (1/2) ln (1 — 2P — Q). Also, formulae for standard errors were obtained. Some examples were worked out using reported globin sequences to show that synonymous substitutions occur at much higher rates than amino acid-altering substitutions in evolution.
26,016 citations
"Epidemiological and Virological Cha..." refers methods in this paper
...The genetic distances were estimated by Kimura’s 2-parameter method, and phylogenetic trees were constructed by the neighbor-joining method [19,20]....
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TL;DR: An overview of the statistical methods, computational tools, and visual exploration modules for data input and the results obtainable in MEGA is provided.
Abstract: With its theoretical basis firmly established in molecular evolutionary and population genetics, the comparative DNA and protein sequence analysis plays a central role in reconstructing the evolutionary histories of species and multigene families, estimating rates of molecular evolution, and inferring the nature and extent of selective forces shaping the evolution of genes and genomes. The scope of these investigations has now expanded greatly owing to the development of high-throughput sequencing techniques and novel statistical and computational methods. These methods require easy-to-use computer programs. One such effort has been to produce Molecular Evolutionary Genetics Analysis (MEGA) software, with its focus on facilitating the exploration and analysis of the DNA and protein sequence variation from an evolutionary perspective. Currently in its third major release, MEGA3 contains facilities for automatic and manual sequence alignment, web-based mining of databases, inference of the phylogenetic trees, estimation of evolutionary distances and testing evolutionary hypotheses. This paper provides an overview of the statistical methods, computational tools, and visual exploration modules for data input and the results obtainable in MEGA.
12,124 citations
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TL;DR: The data suggest that HBV genotype C is associated with more severe liver disease and genotype B may be associated with the development of HCC in young Taiwanese, and additional large-scale longitudinal studies are needed to confirm the relationship ofHBV genotypes to liver disease severity and clinical outcomes.
929 citations