烟台地区慢性乙型肝炎患者病毒基因型分布与临床特征分析

目的了解烟台地区慢性乙型肝炎患者HBV基因型的分布及其与临床的关系。方法采用实时荧光定量PCR法,检测362例慢性乙型肝炎患者HBV基因型,并分析不同基因型之间性别、年龄及ALT、HBV DNA定量、HBeAg状态的差异。结果 362例标本中,B基因型7例（1.9%）,C基因型344例（95.0%）,非B非C型11例（3.0%）。B基因型患者年龄（36.29±17.54）岁,C基因型患者年龄（37±10.64）岁,非B非C型患者年龄（45.09±10.67）岁,P=0.050;两两比较提示C基因型患者年龄较非B非C型患者年龄低,P=0.015,余差异无统计学意义。不同基因型之间性别及ALT、HBV DNA定量、HBeAg状态的差异均无统计学意义。结论烟台地区慢性乙型肝炎患者HBV以基因C型为主,存在少量基因B型及非B非C型。不同基因型患者年龄可能存在差异。     

乙型肝炎病毒的基因型及临床意义

自1988年首次提出乙型肝炎病毒(hepatitis B virus.HBV)基因型以来。关于HBV基因型的研究不断深入,发现不同基因型感染后,临床的病情进展和治疗反应有所差异。虽然各研究结果间有的观点相同,有的观点不同.但这些初步研究结果都为进一步明确HBV基因型的确切临床意义奠定了必要的基础。已知1b型和4型丙型肝炎病毒感染人体后对干扰素治疗的敏感性低于其他基因型;6型和11型人乳头瘤病毒感染常常引起尖锐湿疣。而16、18型则与宫颈癌前病变有关。提示病毒基因型与临床之间确切的关系依病毒不同而有区别。要明确HBV基因型与临床的确切关系,还有待传染病学工作者不断努力,去伪存真,用科学的方法     

镇江地区B、C基因型慢性乙型肝炎临床因素分析

目的：比较B、C基因型慢性乙型肝炎患者（慢乙肝）在临床特征上的差异，总结与C基因型乙型肝炎有关的临床因素。方法：选择经肝穿刺行肝组织病理检查、并经基因型检测确定为B、C基因型的患者共78例，检测血清HBV DNA载量，统计重型肝炎、肝硬化、肝细胞癌和HBeAg阳性发生率，确定肝组织病理炎症分级及纤维化分期。通过x^2检验和多分类Logistic多元回归，分析B、C基因型患者间上述指标的差异，总结与HBVC基因型有关的临床因素。结果：HBVC基因型慢乙肝患者血Alb、前白蛋白均低于B基因型，而ALT、TBil及凝血酶原时间（PT）均高于B基因型，差异有统计学意义。HBVC基因型慢乙肝患者比率随肝组织炎症分级G0～G4（1．8％、11、1％、20．4％、33．3％、33．3％）及纤维分期S0～S4（5．6％、5．6％、14．8％、33．3％、40．7％）进展均明显增加，而B基因型患者随炎症分级（16、7％、25、0％、25、0％、20．8％、12．5％）及纤维分期（16．7％、29．2％、20、8％、16、7％、16．7％）进展变化不大，两种基因型分布与炎症分级（x^2=11．49，P=0．022）及纤维分期（x^2=13.56，P=0．006）差异均有统计学意义。在HBV DNA〉1．0×10^6拷贝／mL时，C基因型患者比率明显高于B基因型（51．8％比12、5％），5．0×10^2～1．0×10^6拷贝／mL时差异不大（35.2％比45．8％），〈5．0×10^2拷贝／mL时明显低于B基因型（13．0％比41．7％），两种基因型分布与DNA载量差异有统计学意义（x^2=13．25，P=0．001）；C基因型慢乙肝患者HBeAg阳性率明显高于B基因型（61．1％比25．0％），差异有统计学意义（x^2=8、67，P=0、003）；C基因型患者发生失代偿期肝硬化比率明显高于B基因型（40．7％比4．2％），未发生肝硬化比率明显低于B基因型者（37.0％比75．0％），两种基因型患者发生肝硬化比率差异有统计学意义（x^2=12.47，P=0．002）。结论：C基因型慢乙肝患者与肝纤维化、炎症损伤程度、HBV标志物、肝硬化发生率及程度等均有较高的相关性。     

乙型肝炎病毒感染者病毒基因型和亚型分布及其临床意义

目的研究不同类型乙型肝炎病毒（HBV）感染者中HBV基因型和亚型分布情况及其临床意义。方法应用基因型和亚型特异性引物聚合酶链反应法（PCR），对北京、长春、汉川，深圳，清远和南京等6个城市445份HBV感染者血清进行基因型及亚型分型，其中急性肝炎7例，无症状携带者36例，慢性乙型肝炎352例，肝硬化28例，肝细胞癌22例。通过对PCR产物测序确定其基因型，以验证该法的准确性。结果445份血清中，239例（53．7％）为C型，其中13例（5．4％）为C1亚型，135例（56．5％）为C2亚型，91例（38．1％）为非C1／C2亚型；145例（32．6％）B型，其中100例（69．0％）为Ba亚型，25例（17．2％）为Bj亚型，20例（13．8％）为非Ba／Bj亚型；61例（13．7％）为B型与C型混合感染，其中6例（9．8％）为Ba与C1亚型混合感染，3例（4．9％）为Bj与C1亚型混合感染，15例（24．6％）为Ba与C2亚型混合感染，8例（13．1％）为Bj与C2型混合感染，11例（18．0％）为Ba与非C1／C2亚型混合感染，7例（11．5％）为Bj与非C1／C2亚型混合感染，2例（3．3％）为非Ba／Bj亚型与C1亚型混合感染，3例（4．9％）为非Ba／Bj亚型与C2亚型混合感染，6例（9．8％）为非Ba／BJ亚型与非C1／C2亚型混合感染。未检测到其他基因型及亚型。在不同类型乙型肝炎病毒感染者中，B型，C型、B与C型混合感染及亚型分布差异有统计学意义，在肝硬化和肝细胞癌患者中C型所占比例较高（分别为78．6％和86．4％），无症状携带者中B型所占比例较高（72．2％）。但不同性别患者中，HBV基因型和亚型分布无差异。在HBeAg阳性和阴性感染者中，HBV基因型和亚型分布差异也有统计学意义。结论该6个城市HBV感染者中，以B2和C2亚型占优势，C基因型可能与肝硬化和肝细胞癌的发生有关。     

沈阳地区650例慢性丙型肝炎病毒感染者的病毒基因型分析

HCV感染呈全球分布,不同基因型和亚型的地理分布,可能与抗HCV治疗的疗程及效果相关.本研究以核酸序列分析法对650例患者进行HCV基因型检测分析,以探讨沈阳地区感染人群中HCV的基因型特征.一、资料与方法     

广东地区原发性肝癌与乙型肝炎病毒基因型的相关性

目的研究广东地区原发性肝癌（HCC）与HBV基因型的相关性。方法2003至2005年慢性HBV感染相关肝脏疾病患者共298例，其中HCC73例，肝硬化（LC）53例，慢性乙型肝炎（CHB）91例，无症状HBV携带者（ASC）81例。采用PCR-限制性片段长度多态性（PCR-RFLP）分析及克隆测序方法对血清HBVDNA进行基因分型，比较各组患者HBV基因型的分布及临床特征。结果298例患者基因型分布为B型142例，占47．65％；C型156例，占52．35％。HBVC基因型在HCC患者分布明显高于其他对照组（X^2=45．20，P〈0．01）。HCC组中男性比例明显高于女性；HCC和LC组平均年龄显著高于其他组。结论广东地区HBV相关性肝病HBV基因型主要为C型和B型，HBVC基因型感染可能为HCC的高危因素之一。     

四川省德阳地区乙型肝炎病毒相关性肝癌患者的病毒基因型分布及其临床特点

原发性肝细胞癌(HCC)是我国临床常见的恶性肿瘤,HBV感染是引起HCC的最主要病因.有研究报道,HBV基因型与HCC的发生有一定的相关性.由于HBV基因型分布存在地域性及种族差异等因素,相关研究在不同地区尚未得出一致的结论.本研究对四川省德阳地区112例HBV相关HCC和1152例慢性HBV感染者进行了研究,以了解该地区HBV相关HCC患者基因型的分布及其临床特点.     

新疆维吾尔族慢性乙型肝炎患者HBV基因型分布及其特点

目的探讨新疆维吾尔族慢性乙型肝炎患者HBV基因型分布及其特点。方法采用型特异性引物巢式PCR法对127例维吾尔族慢性乙型肝炎患者进行基因分型,并测序验证。结果基因D型占39．4%（50/127）,基因B型占22．0%（28/127）,基因C型占16．5%（21/127）,基因BD混合型占9．4%（12/127）,基因CD混合型占8．7%（11/127）,基因BCD混合型占3．9%（5/127）; HBeAg阳性与HBeAg阴性的维吾尔族慢性乙型肝炎患者基因型分布,差异无统计学意义（x^2= 6．033,P＞0．05）;不同年龄维吾尔族慢性乙型肝炎患者HBV基因型分布差异无统计学意义（x^2= 3．137,P＞0．05）;不同性别维吾尔族慢性乙型肝炎患者HBV基因型分布差异亦无统计学意义（x^2= 8．058,P＞0．05）。结论新疆维吾尔族慢性乙型肝炎患者HBV基因型以D型占优势,其次可见B、C型及BD、CD、BCD混合型。同一疾病谱的慢性HBV感染者基因型分布可能与宿主HBeAg状态、年龄、性别无明显关系。     

天津地区家族聚集性慢性乙型肝炎病毒感染者病毒载量及组织病变与基因型的关系

目的探讨天津地区家族聚集性HBV感染患者基因型特征与病毒载量及肝组织病理的关系。方法随机采集临床确诊家族聚集性的慢性HBV表面抗原携带者(ASC)35例和轻型CHB患者65例。分别进行HBV基因分型、HBV DNA载量、肝组织病理学检测。结果HBV基因型显示:B型7例,HBV DNA主要为低载量(57.14%),病理损害程度较轻。BC混合型11例,HBV DNA以低、中载量为主(45.45%、36.36%),病理损害多为轻至中度≤G2 10例(90.91%),≤S2 9例(81.82%)。C型82例,其中ASC 29例,HBV DNA以高载量为主(72.41%),均有不同程度的病理损伤(100%);CHB 53例,HBV DNA主要为中、高载量(39.62%,49.06%),病理损害≥G2者38例(71.70%),≥S2者25例(47.17%)。结论天津地区家族聚集性ASC和CHB以基因C型为主、病毒载量高、肝组织病理损伤较严重,为乙型肝炎预后不良的主要因素;家族聚集性ASC不仅存在HBV病毒高载量,而且均有不同程度的肝脏病理损伤,临床可视肝组织病理结果酌情抗病毒治疗;肝组织病理学检查作为ASC和CHB患者治疗前的常规检测手段,为规范CHB的抗病毒治疗提供可靠依据。     

乙型肝炎病毒Ⅱ型与肝细胞癌

调查了237例肝细胞癌(HCC)患者血清中感染乙型肝炎病毒(HBV)的状态,其中152例(64.14%)HBs Ag阳性,并揭示HCC患者血清中存在HBV_2感染的血清学模式,即HBsAg阳性而抗-HBc阴性,占HBsAg阳性HCC患者的10.53%(16/152)。占所有HCC患者的6.75%(16/237)。应重视对HBV_2感染的防治。     

云南大理白族人群乙型肝炎病毒基因型和亚型的分布

目的调查云南大理地区白族人群乙型肝炎病毒（hepatitis B virus，HBV）基因型和亚型分布情况。方法在大理地区选择100例白族慢性HBV感染者，采用基因型特异性引物分型法和聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法测定HBV感染者血清HBV基因型和亚型，并用ELISA法测定HBV血清标志物。结果100例HBV感染者中，B型41例（41％），全部为Ba亚型，未发现Bj亚型；C型25例（25％），其中Cs亚型21例（84％），Ce亚型3例（12％），未分型1例（4％）；B＋C混合型34例（34％）。B型感染者与C型感染者比较血清HBeAg阳性率差异有统计学意义（P=0．024）。结论云南大理白族人群HBV感染的基因型主要为B型、B＋C混合型和c型，以Ba和cs亚型为主要流行株，B＋C混合型感染占很大比例。     

Detection of hepatitis B virus genotypes using oligonucleotide chip among hepatitis B virus carriers in Eastern China

AIM： TO determine the genotype distribution of hepatitis B virus （HBV） with a newly oligonucleotide chip assay among the HBV carriers in Eastern China. METHODS： An assay using oligonucleotide chip was developed for detection of HBV genotypes in serum samples from HBV DNA-positive patients in Eastern China. This method is based on the principle of reverse hybridization with Cy5-labeled amplicons hybridizing to type-specific oligonucleotide probes that are immobilized on slides. The results of 80 randomly chosen sera were confirmed by direct sequencing. RESULTS： HBV genotype B, C and mixed genotype were detected in 400 serum samples, accounting for 8.3% （n = 33）, 83.2% （n = 333）, and 8.5% （n = 34）, respectively. The evaluation of the oligonucleotide assay showed 100% concordance with the amplicon phylogenetic analysis except 9 mixed genotype infections undetected by sequencing. CONCLUSION： The study indicates that HBV genotype C and B prevail in the Eastern China. It is suggested that the oligonucleotide chip is a reliable and convenient tool for the detection of HBV genotyping.     

回族乙型肝炎病毒基因型分布及其临床意义

乙型肝炎病毒（HBV）分为8种不同的基因型。其型别与患者的病情严重程度及预后等有密切关系，其分布也存在一定的区域及民族差异。为进一步明确回族人群HBV基因型分布情况及其临床意义，进行了此项研究。     

A complete genomic analysis of hepatitis B virus genotypes and mutations in HBeAg-negative chronic hepatitis B in China

Summary.  We aimed to study the distribution of hepatitis B virus (HBV) genotypes/subgenotypes in different parts of China and their clinical impact on the severity of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. Residual serum samples from a cohort of HBeAg-negative chronic hepatitis B patients in Hong Kong, Shanghai and Beijing were studied. Complete HBV genomic sequencing was performed for phylogenetic tree analysis and determination of HBV mutations was carried out. Mutations associated with severe liver fibrosis (Ishak score 4 or more) were selected by computerized information gain criteria. Genotype B (all subgenotype Ba) HBV was present in 19 of 45 (42%), 12 of 31 (39%) and 5 of 25 (20%) patients in Hong Kong, Shanghai and Beijing, respectively ( P  = 0.16). Ninety-seven per cent of genotype C HBV in Shanghai and Beijing belonged to subgenotype Ce whereas 69% of genotype C patients in Hong Kong belonged to subgenotype Cs ( P  < 0.001). Patients infected by subgenotype Cs had the lowest serum albumin and highest alanine aminotransferase levels compared with subgenotype Ce and Ba. Patients infected by subgenotype Cs also had more severe histological necroinflammation than subgenotype Ce. Two HBV mutations were identified to associate with severe liver fibrosis (G2858C and C2289A) and one mutation was protective against severe liver fibrosis (T2201C). The T2201C mutation was found exclusively among patients (21 of 46 patients, 45%) infected by HBV subgenotype Ce. The clinical differences in HBeAg-negative chronic hepatitis B in China may be influenced by different distribution of subgenotype C HBV.     

延边地区朝、汉族慢性乙型肝炎患者血清标志物与HBV DNA定量的关系

目的:探讨延边地区朝、汉族慢性乙型肝炎患者血清HBVM表现模式与HBVDNA含量的关系.方法:采用荧光定量聚合酶联反应(FQ-PCR)和酶联免疫吸附试验(ELISA)检测慢性乙肝患者1773例(朝鲜族1074例,汉族699例)血清HBVDNA含量及HBVM,比较分析朝、汉族HBVM表现模式与HBVDNA含量的关系.结果:HBVM表现模式中朝、汉族在A组(HBsAg 、HBeAg 、HBcAb )各占40.69%、47.07%(P<0.01),B组(HBsAg 、HBeAb 、HBcAb )和C组(HBsAg 、HBcAb )各占47.07%,38.34%及7.18%,4.58%(均P<0.05).两个民族A、B组HBVDNA的阳性率(A:93.82%,93.92%;B:47.54%,47.39%)相似,在A组HBVDNA含量主要以高含量(≥1014-1016copies/L,70.73%,72.17%)为主,B组多数以低含量(≥106-1010copies/L,51.64%,51.18%)为主.结论:延边地区朝、汉族HBVM表现模式有明显差异,但HBVDNA的阳性率相似,HBVDNA含量与HBVM表现模式明显相关.     

新疆地区汉族人群乙型肝炎病毒基因型的分布及其与临床类型的关系

本研究旨在通过型特异性引物巢式聚合酶链反应（PCR）的方法检测新疆地区汉族人群乙型肝炎病毒（HBV）患者HBV基因型并探讨与临床类型的关系，现将结果报道如下。     

Hepatitis B virus genotypes and clinical manifestation among hepatitis B carriers in Thailand

BACKGROUND: Hepatitis B virus (HBV) genotypes have distinct geographic distributions. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Thailand. METHODS: Hepatitis B virus genotypes among 107 hepatitis B carriers residing in Thailand were evaluated using serologic and genetic methods. They were clinically classified into asymptomatic carriers with normal serum alanine transaminase (ALT) levels and patients with chronic liver disease, such as those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). RESULTS: Hepatitis B virus genotype distribution among the 107 patients was 25.2% for genotype B, 72.0% for genotype C and 2.8% for genotype D. The serum ALT levels, HBV-DNA and hepatitis B e antigen positivity were significantly higher in carriers infected with genotype C HBV than in those infected with genotype B (P < 0.05). The proportion of genotype B HBV was higher in asymptomatic carriers than in patients with CH and those who developed liver disease, such as LC and HCC (45.5, 16.9 and 25.0%, respectively; P < 0.05). In contrast, the proportion of genotype C HBV was higher in patients who developed liver disease and CH than in asymptomatic carriers (68.7, 83.0 and 50.0%, respectively; P < 0.05). Phylogenetic analysis based on entire genome sequences revealed three HBV isolates, which were classified into a subgroup of genotype C in isolates from South-East Asian countries. CONCLUSIONS: Genotypes B and C are the predominant types among hepatitis B carriers residing in Thailand and those genotypes influence the clinical manifestation in carriers with chronic hepatitis B infection.     

YMDD mutations and genotypes of hepatitis B virus in northern China

The objective of this research was to determine the relationship between YMDD mutations and the genotypes of hepatitis B virus (HBV) during lamivudine treatment. HBV genotypes were determined by nested PCR with 6 pairs of HBV genotype-specific primers (A to F) in serum specimens from 142 hepatitis B patients receiving lamivudine antiviral therapy. YMDD mutations were detected by fluorescent hybridization bioprobe PCR and melting curve assay (FH-PCR-MC). Among 142 serum specimens, 13 samples were genotype B (9.2%), 125 samples were genotype C (88%), 4 samples were genotype D (2.8%), and 80 YMDD mutations were found. The YMDD mutation rates were 69.2 and 54.4% in genotype B and genotype C, respectively. There was no significant difference in the YMDD mutation rate between genotypes B and C. Nine genotype B sera with YMDD mutations were found, including 2 YIDD mutations and 7 YVDD (M + V) mutations. Sixty-eight genotype C sera with YMDD mutations were found, including 34 mutations I (M + I) and 17 mutations V (M + V). There was a significant difference in the YMDD mutation types between genotypes B and C. Our results suggested that the YMDD mutation rate was 56.3% in patients treated with lamivudine for 2-4 years. YIDD was the main mutation type. The YMDD mutation rate showed no significant difference between HBV types B and C (P > 0.05), while the YMDD mutation types showed a significant difference between HBV types B and C in Northern China (chi2 test = 4.6, P < 0.05).     

Hepatitis B virus taxonomy and hepatitis B virus genotypes

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.     

新疆汉族人群HBV基因型与临床病情的关系

目的了解新疆汉族人群乙型肝炎患者乙型肝炎病毒(HBV)基因型的分布及与临床病情的关系.方法新疆HBV感染者的血清226份,包括慢性乙型肝炎轻度、中度、重度、重型肝炎、肝硬化、肝癌患者.采用型特异性引物巢式PCR方法对血清中的HBV进行基因分型.结果新疆汉族人群HBV基因型以B、C混合型为主,占43.8%(99/226),B型31.46%(71/226),C型24.34%(55/226),未分型1例(0.44%),未见有A、D、E、F型分布.随机选取的4株HBV株经S基因序列的测定证实与本检测结果一致.C型HBV感染者的平均ALT、AST、γ-GT、AKP水平及HBV DNA浓度均高于B型、B+C型者(P＞0.05),C、B+C型TBIL平均水平高于B型,差异有统计学意义(P＜0.05).C型HBV感染者TP平均水平低于B、B+C型患者(P＞0.05).随着病情的加重,C型所占百分比逐渐高于B、B+C型,在LC、HCC中分别为36.4%,27.3%,C型感染者抗HBe阳性率逐渐增高,在HCC中B、C、B+C混合型者中抗HBe阳性率分别为26.7%、42.9%和32.6%(P＞0.05).结论新疆汉族人群HBV患者存在B、C与B+C基因型,以B、C混合型为主,基因型的分布与国内其它地方汉族人群相比有自身特点,且与临床病情有关,除TBIL外,各型在临床生化指标方面差异虽无统计学意义,但认为C型可能与较严重肝病有关,B+C型与HBV感染后病情的关系有待进一步明确.