Hepatitis B virus genotypes

Eight genotypes of hepatitis B virus (A-H) are currently recognized, and subgenotypes have recently been described in four of these genotypes (A, B, C and F). The genotypes show a distinct geographical distribution between and even within regions, and are proving to be an invaluable tool in tracing the molecular evolution and patterns and modes of spread of hepatitis B virus. Structural and functional differences between genotypes can influence the severity, course and likelihood of complications, and response to treatment of hepatitis B virus infection and possibly vaccination against the virus. Although the number of studies on these genotypes has increased dramatically during recent years, much remains to be learnt about their full implications.     

Hepatitis B virus genotypes: a South Pacific perspective

87-91% but still, 0.6% of those that did respond to vaccination became infected. The infection rate of the vaccinated populations in the Pacific Islands ranged between 0.7 and 3.8%, which is comparable to Taiwan. A vigorous polyclonal response This communication discusses the current status of research in the hepatitis B virus in relation to the South Pacific. The hepatitis B virus (HBV) is a small DNA virus--3200 nucleotides. It has a circular genome and replicates through an RNA intermediate giving this DNA virus many characteristics similar to RNA viruses. Viral genomes can be single-stranded (+ or - sense) or double-stranded. If not vaccinated, infants born to HBeAg positive mothers (i.e. with high viral titer) have a 90% chance of being infected and becoming HBV carriers themselves. Mutants that affect the major antigenic determinant in HBV surface antigens are probably responsible for HBV infection despite immunization and mutants in the polymerase protein may render HBV resistant to therapy with nucleoside analogs. Within HBV seven genotypes A-G have been reported that is, HBV genotype A (HBVA), HBV genotype B (HBVB) etc. HBV is endemic worldwide with an estimated that 5% of the worlds population being carriers. Before the introduction of vaccination programs carrier rates varied between 5-30% in communities of these ethnic groups, and in some cases 80-90% of a community tested positive for HBV markers (i.e. were infected or had been infected). In Taiwan, of vaccinated babies born to HBV positive mothers, the proportion of those that responded to vaccination varied between will usually result in an acute infection and viral clearance. An associated problem with HBV, in the South Pacific, is the hepatitis delta virus (HDV). HDV is a satellite viroid-like RNA virus that requires HBV for replication. It can either co-infect with, or super-infect upon HBV infection resulting in acute infection and/or chronic infection respectively.     

Heterogeneous recombination among Hepatitis B virus genotypes

The rapid evolution of Hepatitis B virus (HBV) through both evolutionary forces, mutation and recombination, allows this virus to generate a large variety of adapted variants at both intra and inter-host levels. It can, for instance, generate drug resistance or the diverse viral genotypes that currently exist in the HBV epidemics. Concerning the latter, it is known that recombination played a major role in the emergence and genetic diversification of novel genotypes. In this regard, the quantification of viral recombination in each genotype can provide relevant information to devise expectations about the evolutionary trends of the epidemic. Here we measured the amount of this evolutionary force by estimating global and local recombination rates in > 4700 HBV complete genome sequences corresponding to nine (A to I) HBV genotypes. Counterintuitively, we found that genotype E presents extremely high levels of recombination, followed by genotypes B and C. On the other hand, genotype G presents the lowest level, where recombination is almost negligible. We discuss these findings in the light of known characteristics of these genotypes. Additionally, we present a phylogenetic network to depict the evolutionary history of the studied HBV genotypes. This network clearly classified all genotypes into specific groups and indicated that diverse pairs of genotypes are derived from a common ancestor (i.e., C–I, D–E and, F–H) although still the origin of this virus presented large uncertainty. Altogether we conclude that the amount of observed recombination is heterogeneous among HBV genotypes and that this heterogeneity can influence on the future expansion of the epidemic.     

泉州地区乙型肝炎病毒基因型调查及其流行病学研究

目的:初步确定流行于泉州地区的乙肝病毒的基因型的基本情况,并探讨HBV基因型的流行病学特点及其与HBVDNA、HBeAg阳性率的关系。方法:采用分层多阶段随机抽样法收集慢性HBV感染者的血清,应用荧光定量PCR方法对乙型肝炎病毒进行DNA定量和基因型测定,并用SPSS8.0统计软件进行分析。结果:泉州地区的HBV基因型分布分别为B型52.36%,C型46.06%和B/C混合型1.58%。B型患者平均年龄28.99岁、C型慢性乙肝患者平均年龄31.28,C基因型大于B基因型,但两者差异无统计学意义。性别构成比中B型男性多于女性,C型女性多于男性,它们的差异都具有显著性。HBeAg阳性者中B和C这2种基因型分别占55.64%和47.86%;HBVDNA高载量中B基因型(48.72%)多于C基因型(23.08%)。结论:泉州地区HBV携带者HBVDNA阳性者中以B、C型为主,B型占优越,存在少量B和C基因型混合感染。     

Hepatitis B virus genotypes from European origin explains the high endemicity found in some areas from southern Brazil

Southern Brazil is considered an area of low Hepatitis B endemicity, but some areas of higher endemicity have been described in the Southwest of Paraná and Santa Catarina states. The aim of this study was to evaluate viral genotypes circulating throughout Paraná state. PCR amplification and partial sequencing of the S gene was carried out in 228 samples from HBsAg positive candidate blood donors. Samples have been collected in seven different counties (Cascavel, Curitiba, Foz do Iguaçu, Francisco Beltrão, Maringá, Londrina and Paranaguá). The most common HBV genotype in Paraná state was D (82.9%; 189/228), followed by A (14.1%; 32/228). Genotypes F (1.3%; 3/228), C (1.3%; 3/228) and H (0.4%; 1/228) were also found. Distribution of genotypes was different in the studied counties, but genotype D was the most frequent in all of them. In Francisco Beltrão, all studied samples belonged to genotype D. The high prevalence of HBV genotype D in South of Brazil is explained by the intense migration of settlers from Europeans countries. Subgenotypes A1 and A2 were identified circulating in all cities where HBV/A was found. As observed in other areas of Brazil, HBV/A1 is more frequent than the HBV/A2 in Paraná state and its presence was significantly larger in black and mulatto individuals. Genotype C was found only in individuals with Asian ancestry from Londrina and Maringá. Most HBV/F sequences identified in this study were classified as subgenotype F2a that was previously described in Brazil. The sole case of subgenotype F4 was from Foz do Iguaçu city, near to Northern Argentina, where F4 is highly prevalent. The single genotype H sample was from Curitiba. This is the first case of this genotype described in Brazil. Further studies should be carried out to determine if more genotype H samples can be found in other populations from Brazil.     

Pattern and molecular epidemiology of Hepatitis B virus genotypes circulating in Pakistan

The continuously mutating nature of Hepatitis B virus (HBV) is responsible for the emergence of varying genotypes in different regions of the world affecting the disease outcome. The objective of the current study was to find out the pattern of HBV genotypes circulating in Pakistan. HBV genotypes were determined in HBV chronic patients of different age and gender from all the four different geographical regions (provinces) of Pakistan for a period of 2 years (2007–2009). Out of the total 3137 consecutive patients, 300 (175; 58.3% males and 125; 41.7% females) were randomly selected for HBV genotype A through H determination using molecular genotyping methods. Total 269 (89.6%) isolates were successfully genotyped where as 31 (10.3%) samples failed to generate a type-specific PCR band and were found untypable. Out of the successfully genotyped samples, 43 (14.3%) were with type A, 54 (18%) were with type B, 83 (27.6%) were with type C, 39 (13%) were with type D, 2 (0.6%) were with type E, 4 (1.3%) were with genotype F and total 44 (14.6%) were with mixed HBV infections. Of the mixed genotype infection cases, 16 were with genotypes A/D, 9 were B/C, six were A/D/F, five were with genotypes A/F, two were with A/B/D and B/E and one each for A/C as well as A/E genotypes. Four common genotypes of HBV found worldwide (A, B, C & D) were isolated from Pakistan along with uncommon genotypes E and F for the first time in Pakistan. Overall Genotype C is the most prevalent genotype. Genotypes B and C are predominant in Punjab & Balochistan and Khyber Pakhtoonkhwa, respectively whereas genotype A in Sindh.     

Hepatitis B virus (HBV) genotypes in the Czech Republic

Hepatitis B virus (HBV) was genotyped based on sequencing and analysis of nucleotide sequences of HBV S gene in sera samples from 176 patients with viral hepatitis B from all over the Czech Republic. The most frequent genotype A was detected in 118 (67.1%) of the patients, followed by genotype D found in 50 (28.4%) of the patients. Genotypes B and C were identified in 6 (3.4%) and 2 (1.1%) of the patients, respectively. The incidence of genotype A statistically significantly increases with age. There is no statistically significant correlation between genotypes A and D and gender or locality (region). Genotypes B and C, found mainly in South East Asia, were first detected in the Czech Republic. Detection of these genotypes in both foreigners and Czech population is suggestive not only of import but also of transmission of these genotypes in the Czech Republic. Fylogenetic analysis documents dissimilarity levels between HBV isolates. Based on the amino sequence derived, the percentages of HBV subtype determinants d (68.6%) and y (31.4%) were established. The gene S sequencing analysis proved suitable for HBV genotyping.     

深圳市劳务工乙型肝炎病毒基因分型及临床意义

目的:研究深圳市劳务工乙型肝炎病毒(HBV)感染者中HBV的基因分型及临床意义。方法:应用荧光定量聚合酶链反应法(荧光PCR),对178份HBV-DNA阳性的乙型肝炎病毒感染者血清进行HBV基因分型。结果:178份血清样品中B型116份(65.17%),C型43份(24.16%),B+C混合型13份(7.30%)。男女之间平均年龄存在统计学差异(P<0.05);C型的HBeAg阳性率高于B型(P<0.05),而HBV-DNA水平低于B型,但比较无统计学意义;来自华南地区的劳务工检出HBV基因型最多。结论:深圳市劳务工流行的HBV基因型主要为B型,同时存在C型和少量的B+C混合型;HBV基因型与其致病性存在相关性。     

乙型肝炎病毒基因型及其变异与抗病毒疗效

近年来,虽然对HBV有关HBV基因型、基因变异及其在临床上的应用研究取得了一些新的进展,但仍有许多问题尚未解决。目前研究的热点集中在HBV基因型的特点及临床意义、HBV聚合酶基因变异与核苷类似物耐药性的研究。现就国内外HBV基因型、基因变异及抗病毒治疗关系的研究现状综述如下。     

中国丙型肝炎病毒基因型分布

目的分析中国丙型肝炎病毒(HCV)基因型的分布及变化趋势。方法计算机检索1994年以来中国医院知识库(CHKD),1998年以来万方数据资源系统、中国生物医学文献数据库(CBMDisc)以及PubMed数据库,并结合文献追溯方法,收集国内HCV基因分型的相关文献。相同HCV亚型分别按地区、研究时间、人群分组,并进行简单数量合并,计算百分比。结果共纳人文献140篇(共168条记录)。不同地区HCV基因型存在差异,其中北方地区基因型较单一,以1b和2a型为主;南方地区HCV基因型种类较多,以1b型为主,2a,3a,3b及6a型各自占较大比例。早期HCV基因型较单一,随着时间推移,1b及2a亚型逐渐减少,而3a,3b及6a亚型逐年增加,亚型类型逐年增多。有偿献血人群lb,2a亚型所占比例较高;吸毒人群HCV基因亚型较多,3型(3a,3b亚型)及6a亚型所占比例较大,且有逐渐向普通人群扩散趋势。结论中国流行最广泛的HCV基因亚型为1b及2a,且分布地区差异较大,并随时间的推移,基因型分布产生较大变化。     

Hepatitis C virus genotypes in southern Taiwan: prevalence and clinical implications

The role of hepatitis C virus (HCV) genotypes in the development of hepatocellular carcinoma (HCC) is still controversial. To determine the distribution and clinical implications of HCV genotypes in southern Taiwan, we analysed 418 patients with chronic HCV infections. HCV genotypes were determined using an HCV Line Probe Assay. The predominant HCV genotype was 1b (45.5%), followed by 2a/2c (30.9%) and 2b (6.9%). The prevalence of genotype 1b in HCC patients (60.3%) was significantly higher than in those with liver cirrhosis (38.7%) and chronic hepatitis (38.7%) (P=0.003 and P<0.001, respectively). Patients with chronic HCV 2a/2c infection had higher alanine aminotransferase (ALT) levels than those with chronic HCV 1b infection (P<0.001). Univariate analysis revealed that disease severity was significantly correlated with older age, genotype 1b, lower ALT levels and lower viral load. Based on multiple logistic regression analysis, after adjusting for age and serum HCV RNA levels, HCV 1b infection was still a significant risk factor for HCC. In conclusion, the predominant genotypes in southern Taiwan were 1b and 2a/2c, and disease severity was associated with genotype 1b.     

Epidemic history of Hepatitis C virus in Brazil

Hepatitis C virus (HCV) subtypes 1a, 1b and 3a are the most prevalent strains in Brazil, but very little is known about the epidemic history of these subtypes in the country. A total of 231 HCV NS5B gene sequences (subtype 1a = 89, subtype 1b = 56, and subtype 3a = 86) isolated in Brazil between 1995 and 2007 were analyzed in the present study. Sequences (328-pb) were subjected to phylogenetic analyses and statistical tests of phylogenetic mixing by sampling location and risk group. Our results revealed important variations in the pattern of HCV transmission among subtypes. Transmission of subtype 1a was characterized by dissemination of one major Brazilian lineage with a random virus exchange between different geographical regions but not between IDU and non-IDU populations. Transmission of subtype 1b was characterized by concurrent dissemination of multiple HCV lineages with a restricted virus exchange between country regions and risk groups. Transmission of subtype 3a was characterized by simultaneous spreading of multiple HCV lineages and random phylogenetic mixing by risk group and sampling location. Epidemic histories of major subtypes 1a, 1b and 3a Brazilian clades were estimated using a Bayesian coalescent approach. Our results indicate that all major HCV Brazilian clades probably start to circulate in the country during the second half of the 20th century and displayed roughly similar epidemic histories characterized by an initial phase of exponential expansion and by reduction of growth rates since 1980–1995. This suggests that the expansion of HCV may have been effectively controlled in Brazil.     

中国乙型肝炎的流行及控制进展

  目的  调查分析深圳市罗湖区2010 — 2020年乙肝携带、新发感染和乙肝相关疾病死亡率流行特征,评估示范区乙肝综合防治效果。  方法  利用多阶段整群随机抽样的方法,分别于2010年和2020年对罗湖区进行乙肝携带率调查,同时收集了示范区罗湖区和对照区龙岗区2010 — 2020年乙肝新发感染、乙肝相关疾病死亡及人口学资料,运用描述性流行病学的方法,分析罗湖区乙肝携带率、新发感染率和相关疾病死亡率的现况和变化趋势。  结果  罗湖区2010年和2020年标化后的乙肝携带率分别为8.74 % 和6.91 %,差异具有统计学意义（P < 0.01）。乙肝新发感染率由2010年的2.88/10万下降至2020年的0.09/10万,下降了96.88 %。乙肝相关疾病的标准化死亡率2010年和2020年分别为5.36/10万和5.67/10万,变化趋势整体呈平稳状态,差异无统计学意义（P = 0.561）。罗湖区与龙岗区横向比较显示,2010 — 2020年罗湖区乙肝新发感染率均低于龙岗区,差异均有统计学意义（P < 0.05）;罗湖区在2010 — 2015年内乙肝相关疾病的标准化死亡率均高于龙岗区,2016 — 2017年两区基本持平,自2018年起,罗湖区低于龙岗区,差异有统计学意义（P < 0.05）。  结论  病毒性肝炎综合防治重大科技专项在深圳市罗湖区经过10年的努力取得显著成效,逐步形成了可推广的乙肝社区综合防治模式。     

Hepatitis B virus markers among teenagers in the Araguaia region, Central Brazil: assessment of prevalence and vaccination coverage

The Brazilian hepatitis B (HBV) vaccination program for neonates was implemented in 1998 and broadened to include young people up to 20 years of age in 2001. However, HBV coverage of teenagers has not been systematically assessed in Brazil.A cross-sectional study was performed to estimate the magnitude of HBV infection and vaccine coverage among adolescent students regularly enrolled in the public schools of Barra do Garças, a city located in the state of Mato Grosso, Brazil. A representative sample was randomly obtained and participants were interviewed and had blood samples collected to test for HBV markers.The sample was composed of 576 subjects, 51% of which were females. The average age was 15, with the group ranging from 12 to 20 years of age. There were 29 anti-HBc reactive participants (5.0%). Four out of 29 were HBsAg positive (0.7%). Anti-HBs alone (vaccinated profile) showed in 323 (56.1%) students and 224 (38.9%) were negative for all HBV markers. Increasing age was associated with HBV exposure in a χ² for trend analysis (p = 0.004). The prevalence of anti-HBs alone decreased as the subjects’ age increased. Multivariate analysis showed independent association between HBV infection and the start of sexual activity. Another associated variable was the fact that the some students were enrolled in two low-income neighborhood schools.Our findings classify this area as low endemic for HBV and suggest that there is a progressive decrease in the spread of HBV in the region due to the introduction of universal vaccination of neonates. Approximately half of the adolescents 15 years or older were not immunized, which raises a concern in terms of the need to increase the vaccination rate for this segment of the population.     

Hepatitis B virus DNA polymerase

Our aim was to discuss the practical value of HBV DNA polymerase (DNAp) determination. DNAp activity is a good marker of HBV high replication in patients with chronic hepatitis B (HBeAg+), very useful during monitoring of immunostimulation and/or antiviral treatment.     

Hepatitis B virus and persistent antigenemia in adolescents

Adolescents attending a municipal outpatient adolescent clinic in New York City were evaluated for the prevalence of hepatitis B virus (HBV) markers and persistent antigenemia. Among 313 teenagers tested in 1 year, 11.8% were HBV marker positive, and 4.8% had persistent antigenemia. Hispanic teens had a marker rate of 6.4% and an antigenemia rate of 1.4%. Dominican Republic teens had a significantly higher marker rate than Puerto Rican teens. Among Hispanics, sexual activity status and foreign- vs. U.S.-born status were not significantly related to the presence of HBV markers. Asian teenagers had a 50% marker rate and a 27.2% rate for persistent antigenemia. Marker and antigenemia rates were highest in the most recent immigrants. Unexplained persistent hematuria occurred more frequently in patients with HBV markers than in patients without markers. We recommend routine hepatitis B surface antigen screening in Hispanic and Asian adolescents. The greatest at-risk groups are Asians, especially recent immigrants, immigrants from the Dominican Republic, and probably patients with unexplained persistent hematuria.     

Hepatitis B virus replication and tuberculin reactivity: studies in Alaska

In a previous study in 1982-1984 of southeast Asian refugees in Philadelphia, the authors found that hepatitis B virus carriers who reacted to a tuberculin (purified protein derivative (PPD)) skin test were more likely to be negative for the hepatitis B e antigen (HBeAg) than carriers who did not react to PPD. Because it was not known whether the PPD reactivity was due to natural infection or vaccination with bacille Calmette-Guérin (BCG), the authors conducted a further study in 1985 in Alaskan Native hepatitis B carriers, a group not vaccinated with BCG. The inverse association of HBeAg and PPD reactivity was confirmed across all age groups and was similar in magnitude to that observed in the refugee population. The host response to tubercle bacilli may inhibit the replication of hepatitis B virus. If the host response to BCG is similar, BCG vaccination may be of therapeutic value in chronic hepatitis B infection.