鲁南地区HBV基因型和HBV核心启动子双点突变与肝硬化、肝癌的关系

目的研究鲁南地区肝细胞癌(HCC)、肝硬化(LC)患者与乙型肝炎病毒(HBV)基因型及基本C区启动子(BCP)基因区A1762T/G1764A双位点变异之间的关系,探讨其相关性。方法按慢性HBV感染者111例的不同临床分型,对其中HCC、LC和慢性乙型肝炎(CHB)患者各37例,采用实时荧光定量PCR法及PCR微板核酸杂交ELLSA技术进行HBV基因定量、分型检测;采用HBV基因多态性芯片检测BCP区A1762T/G1764A双位点变异;对不同性别、年龄、病毒基因型分布、临床分型患者进行HBV基因分型、BCP区双突变,以及不同HBV基因型BCP双突变的比较。结果在CHB、LC、HCC患者中,HBeAg阴性者分别为24.3%、75.7%和83.8%;HCC患者HBeAg阴性率较CHB患者明显升高(P<0.05)。男、女性别HBV均以C基因型占优势,分别为57.3%和54.5%,性别间无统计学差异(P>0.05);年龄<30岁组HBV以B基因型(40.3%)、C基因型(51.7%)占优势,≥30岁组以C基因型(67.2%)占优势,<30岁组B基因型构成比高于≥30岁组(29.6%,P<0.05);HCC、LC患者中HBV以C基因型为主,分别占73.0%和75.6%。BCP双突变率在HCC、LC分别为64.9%和56.8%;HBVC基因型多发生BCP双突变,占63.6%(42/66)。结论鲁南地区HBV基因型以C型和B型为主,其中LC、HCC患者基因型以C型占优势,HCC患者BCP双突变率显著高于CHB患者,在慢性HBV感染者中HBVC基因型多发生BCP双突变。     

自贡地区HBV基因BCP区1762/1764及前C区1896位点突变与HBV相关性肝癌的相关性研究

目的通过分析自贡地区乙肝患者乙型肝炎病毒HBV基因BCP区1762/1764及前C区1896位点的突变情况,探讨其与HBV相关性肝癌的关系。方法收集2015年9月至2018年6月141例经本院确诊的乙肝性相关疾病患者血清标本(HBV DNA≥103IU/mL):慢性乙肝(CHB组)50例、肝硬化(LC组)45例、肝癌(HCC组)46例,并收集临床相关资料。采用荧光定量PCR法检测患者的HBV DNA水平,多通道荧光PCR法检测HBV基因型,然后采用ARMS-PCR法检测HBV基因BCP区1762/1764及前C区1896突变情况。采用SPSS17.0软件对数据进行统计学分析。结果HCC组和CHB组在e抗原阳性率、HBV DNA水平及HBV DNA>105IU/mL方面对比发现差异均具有统计学意义(P<0.05);HCC组和LC组在e抗原阳性率方面比较发现差异无统计学意义(P>0.05),而HBV DNA水平方面差异具有统计学意义(P<0.05)。男性、女性乙肝患者HBV基因BCP区1762/1764位点突变率分别为67.0%、57.1%(P>0.05),前C区1896位点突变率分别为61.6%、66.7%(P>0.05)。HCC组患者、LC组患者、CHB组患者的HBV基因BCP区1762/1764突变率分别为91.3%、84.4%、22%,HCC组与CHB组比较差异具有统计学意义(P<0.05),而HCC组与LC组比较差异无统计学意义(P>0.05);HBV基因前C区1896突变率分别为84.8%、62.2%、42.0%,HCC组与CHB组、LC组比较差异均具有统计学意义(P<0.05)。HCC组患者的HBV基因前C区1896和BCP区1762/1764位点同时突变率为78.3%,要高于LC组和CHB组,差异均具有统计学意义(P<0.05)。HBV基因型方面比较,无论是基因B型还是C型的乙肝相关患者,疾病进程较重(HCC组、LC组)的受试者携带BCP区1762/1764突变型或前C区1896突变型的比例都要高于慢性乙肝患者(CHB组)。结论自贡地区HBV基因BCP区1762/1764和前C区1896突变率高,无性别和基因型差异,其中HBV基因BCP区1762/1764位点和前C区1896位点联合突变与HBV相关性HCC发生可能存在一定关系。     

拉米夫定抗HBV疗效与其基因型的关系

目的：探讨乙型肝炎病毒（HBV）基因型与拉米夫定抗HBV疗效的关系。方法；采用前瞻性和回顾性相结合的方法收集资料，患者口服拉米夫定100mg·d^-1治疗至少12个月，停药观察至少6个月。采用多引物对巢式PCR法检测HBV基因型，并对停药后HBVDNA阳性者用PCR-序列分析法检测病毒前C（PC）区和C区基本核心启动子（BCP）突变。结果：53例慢性HBV感染患者中C基因型占45．3％，B基因型41．5％，B＋C混合基因型为3．8％，未测出A、D、E、F型。B、C基因型患者的病毒学应答在服药6个月、服药12个月及停药时无统计学差异，停药6个月后的病毒学应答有统计学差异，B基因型优于C基因型。两组患者的PC变异率差异无统计学意义，但BCP变异率差异有统计学意义，C基因型更易发生BCP变异。结论：B基因型患者停药6个月后的持续病毒学应答优于C基因型，C基因型较B基因型更易发生BCP变异。     

HBV感染不同时期基因分型和P基因区点突变及其意义

目的探讨乙型肝炎病毒(HBV)基因型及耐药位点变异在不同类型HBV感染患者中的分布及意义。方法收集40例急性乙型肝炎(AHB)患者、53例慢性乙型肝炎(CHB)患者、44例乙型肝炎肝硬化(LC)患者和32例肝细胞肝癌(HCC)患者血清标本,用PCR扩增及基因测序技术进行基因分型,并对各组患者的HBV DNA载量及血清标志物进行测定。结果不同临床类型(AHB、CHB、LC、HCC)患者拉米夫定(LAM)耐药率及阿德福韦酯(ADV)耐药率分布为11.25%(19/169)、4.73%(8/169);HBV感染者基因型为B型和C型,未见其他基因型;C型年龄分布高于B型(t=2.48,P<0.05);AHB、CHB、LC、HCC患者HBV基因型分布差异有统计学意义(χ2=37.86,P<0.05)。结论苏州地区HBV感染者基因型为B型和C型,且HBV C型更易导致严重肝病的发生。     

乙型肝炎病毒感染与肝细胞癌相关性的多因素研究

目的了解宿主遗传、免疫以及病毒等因素在肝细胞癌(HCC)形成中的作用,探讨乙型肝炎病毒(HBV)感染与HCC形成的多因素相关性。方法选择慢性乙型肝炎(CHB)87例、乙型肝炎肝硬化(LC)38例和HCC 34例,分别对其进行HLA-DR基因型、血清IFN-γ和TNF-α水平、HBV基因型及其前C区1896位和BCP区1762/1764位基因变异情况的检测。结果单因素分析发现,HCC组和LC组的HLA-DR13基因频率、血清TNF-α水平、HBV前C区1896位和BCP区1762/1764位基因变异率均高于CHB组,有显著性差异(P<0.05)。而血清IFN-γ水平和HBV基因型在CHB组、LC组和HCC组间无显著性差异(P>0.05)。Logistic回归分析结果显示,血清TNF-α水平升高和HBV前C区G1896A变异是HCC和LC的危险因素。结论血清TNF-α水平升高和HBV前C区G1896A变异是HBV相关HCC形成的危险因素,可能在HCC形成中具有重要意义。     

探讨前C区A1896变异与乙型肝炎病毒相关的进展性肝病的关系

目的探讨前C区A1896变异与乙型肝炎病毒（HBV）相关的进展性肝病的关系。方法选择172例HBV感染者,采用PCR-RFLP进行A1896变异的检测,并对其临床意义进行分析。结果172例患者A1896变异的总体检出率为45.9%。在A1896变异株和野生株中,慢性无症状携带者（ASC）、慢性乙型肝炎（CHB）、肝硬化（LC）、慢性重型肝炎（CSH）、肝细胞癌（HCC）的构成比差异有统计学意义（P〈0.05）。CHB、LC、CSH、HCC的A1896变异率分别为39.7%、52.0%、50.0%、74.1%,显著高于ASC的12.5%（P〈0.05）。进展性肝病（包括CSH、LC、HCC）的A1896变异率为59.0%,显著高于CHB的39.7%（P〈0.05）。慢性乙型肝病不同临床类型的A1896的野生株、变异株构成比差异无统计学意义（P〉0.05）。HBeAb阳性组的A1896变异率为73.2%,显著高于HBeAg阳性组的28.1%（P〈0.05）。A1896野生株HBeAg阳性率显著高于变异株（45.2%vs 19.0%,P〈0.05）。变异株HBV-DNA复制的均数水平显著高于野生株[（9.55±4.65）lg copies.L-1vs（10.35±4.49）lg copies.L-1,P〈0.01]。结论A1896变异与HBV相关的进展性肝病有关,但与CHB的炎症活动程度无关。A1896变异株的HBeAg阴性率和HBV-DNA病毒载量较野生株高,前者使HBV易逃避免疫清除,后者引起疾病逐步进展。     

乙型肝炎病毒基本核心启动子区A1762T/G1764A突变检测的意义

目的探讨乙型肝炎(乙肝)病毒(HBV)基本核心启动子区(BCP)A1762T/G1764A联合突变在不同疾病中发生的差异及其与乙肝相关肝癌预后的关系。方法选择慢性乙肝(CHB)患者38例、乙肝肝硬化(LC)患者36例、乙肝相关肝细胞肝癌(HCC)患者74例,用巢式PCR扩增患者血清中HBV BCP区,直接测序法检测HBV BCP区变异,分析A1762T/G1764A突变与HBV复制、HBeAg表达和HBV感染不同阶段的关系,以及与HCC患者预后的关系。结果在148例患者中,A1762T/G1764A突变总体发生率为54.7%,乙肝相关HCC组中A1762T/G1764A突变发生率为79.7%,而CHB、LC患者分别为31.6%、27.8%,HCC组变异的发生率明显高于CHB组(P0.05)和LC组(P0.05);A1762T/G1764A突变组HBV-DNA载量与非突变组比较差异无统计学意义(P0.05);HBeAg阳性组A1762T/G1764A突变发生率为41.4%,HBeAg阴性组为73.5%,HBeAg阴性组变异发生率明显高于HBeAg阳性组(P0.05);HCC患者A1762T/G1764A变异组与非变异组之间无病生存期及总体生存期差异无统计学意义(P0.05)。结论 HBV核心启动子区A1762T/G1764A联合突变与HCC发生具有显著关系,该变异与血清HBV-DNA的复制水平无关,但与血清HBeAg表达水平有关,与乙肝相关HCC预后无显著关系。     

不同基因型的乙型肝炎病毒基因变异状况分析

目的研究不同的HBV基因型前C区的第1896位、基本核心启动子（BCP）区第1762位和第1764位双变异的规律及其与临床的关系。方法分别用基因芯片和基因测序的方法检验HBV—DNA阳性的乙型肝炎病毒携带者（ASC）26例、慢性乙型肝炎（CHB）186例、肝硬化（HLC）69例、肝细胞癌（HCC）26例、重型肝炎（FHF）34例的基因型和部分点突变，并比较基因型与基因变异、临床类型与基因变异的关系。结果各临床型间第1762位和第1764位双变异差异显著，ASC组与CHB组、HLC组、HCC组和FHF组相比较，X^2分别为10．8985、42．4086、14．0159、21．7324，P分别为0．0010、0．0000、0．0002和0，0000；基因型B与C型的第1762位、第1764位双突变相比，X^2=48．1395，P=0．0000。结论基因型的存在决定了HBV的某些其他基因变异的方向和频率，从而也决定了因此而造成的肝损伤的程度。     

乙肝病毒基因变异和基因型(亚型)与肝细胞癌的关系

目的 初步探讨乙肝病毒基因变异、基因型及亚型与HCC发病的相关性。 方法 特异探针杂交法检测乙肝病毒C启动子变异，分别用特异探针杂交和特异引物PCR两种方法鉴定病毒基因型，限制性酶切片段长度多态性法鉴定部分HCC乙肝病毒的基因亚型。用SPSS10.0进行统计分析其中相关性。 结果 HCC组与NHCC组HBV-DNA载量无显著差异，两组HBV中A1762T/G1764A变异株分别占77.8%和44.4%。B和C型为HBV主要基因型，基因型B和C在HCC患者中分别为3例（11.11%）和24例（88.89%），在NHCC患者中分别为29例（42.65％）和21（50.85％），HCC组24例基因型C的HBV中21例为C2亚型。 结论 乙肝病毒C启动子A1762T/G1764A双变异、基因型C与HCC的发生密切相关，HCC患者HBV基因亚型主要为C2亚型。     

江苏省南通地区乙型肝炎病毒基因分型与临床相关性

目的了解江苏省南通地区乙型肝炎病毒(HBV)基因型分布状况及其临床相关性。方法选择南通地区HBV-DNA阳性的乙型肝炎病毒感染者300例,其中乙型肝炎表面抗原携带者(ASC)28例,慢性乙型肝炎(CHB)189例,重型肝炎(CSH)26例,肝硬化(LC)30例,肝细胞癌(HCC)27例,采用多对型特异性引物巢式PCR法检测HBV基因型。结果300份血清标本中B型89例(29.7%),C型196例(65.3%),BC混合型15例(5.0%);C基因型在LC组、HCC组中的比例显著高于ASC组和CHB组(P<0.05)。结论南通地区HBV基因型可能以B、C型为主,C型为优势基因型并与肝硬化、肝癌的发生相关。     

慢性乙型肝炎乙型肝炎病毒核心启动子区和前核心区基因变异后的预后分析

目的 为了解慢性乙型肝炎患者乙型肝炎病毒(HBV)核心启动子(BCP)区和前核心(前C)区基因变异后的临床转归及其预后。方法 采用DNA序列分析法检测123例HBV DNA阳性的慢性乙型肝炎患者血清HBV BCP区(nt1762、nt1764)和前C区(nt1896)基因序列,并同步进行乙型肝炎e抗原(HBeAg)、乙型肝炎e抗体(抗-HBe)定量及肝功能检测。结果 123例患者HBV BCP区(A1762T、G1764A)和前C区(G1896A)基因变异检出率为76.42％;其中肝炎肝硬化(HLC)患者双变异(A1762T、G1764A)和联合变异(A1762T、G1764A、G1896A)率最高(52．94％与29．41％);慢性重型肝炎患者终止变异(G1896A)率最高(42．86％);HBeAg／抗HBe转换率分别为：双变异组23.91％,终止变异组75．00％,联合变异组84．00％,无变异组13．79％。结论 HBV BCP双变异、前C终止变异和联合变异均可引起慢性乙型肝炎病情加重及肝硬化的发生,但严重肝损伤与这3种变异之间可能无因果关系,只是HBV减少病毒蛋白的产生,逃避免疫监视的一种方式;推测BCP双变异和联合变异可能是引起HLC的重要病因之一;BCP区变异患者时干扰素治疗敏感。     

Nucleic acid sequence analysis of basal core promoter/precore/core region of hepatitis B virus isolated from chronic carriers of the virus from Kolkata, eastern India: low frequency of mutation in the precore region

OBJECTIVE: The aim of the present study was to characterize the predominant hepatitis B virus (HBV) strains and their molecular variants present in the HBV isolates of the different genotypes found among the chronic carriers of the virus in our community. METHODS: Precore/core and core promoter regions of HBV DNA were amplified by polymerase chain reaction and then subjected to direct sequencing. Of the 64 hepatitis B surface antigen (HBsAg)-positive chronic HBV carriers investigated, 44 were HBeAg negative and 20 were HBeAg positive. RESULTS: In addition to genotype D, which was the predominant genotype, 12 genotype C (18.7%) and 6 genotype A (9.4%) were also detected. Presence of T at nt 1858 has often been related to the development of precore stop mutation at nt 1896, while that of C has been related to the development of 1762-1764 double mutation. In our study group, 39 of the 44 HBeAg-negative samples have T1858. The precore stop codon mutation was found in only 8 (18%) of the HBeAg-negative samples. More than half of the HBeAg-negative samples had wild-type sequence in the precore region. The core promoter region could be sequenced from 40 samples, and 1762-1764 double mutation was detected in 13 (32.5%) of them. No significant changes could be detected in the core amino acid sequence of these isolates. CONCLUSION: The pattern of core promoter and precore mutation of HBV isolates in the present study is atypical and not in accordance with reports from other parts of the world, where genotype D and genotype C with T at codon 1858 are common.     

Precore wild-type hepatitis B virus with G1896 in the resolution of persistent hepatitis B virus infection

OBJECTIVE: Factors influencing the resolution of persistent hepatitis B virus (HBV) infection were sought for. METHODS: The loss of hepatitis B surface antigen (HBsAg) from serum was correlated with mutations in HBV DNA for a hepatitis B e antigen (HBeAg)-minus phenotype in patients infected with HBV genotype C and positive for HBeAg at presentation. RESULTS: HBeAg turned negative in all the 22 patients in whom HBV infection resolved, but only in 11 of the 25 patients with severe liver diseases (100 vs. 44%, p = 0.0001). The precore wild type (G1896) persisted significantly more frequently in the 22 patients in whom HBV infection resolved than in the 11 patients who developed decompensated liver cirrhosis or hepatocellular carcinoma (15/22 or 68% vs. 1/11 or 9%, p = 0.005). The double mutation in the core promoter (T1762/A1764) was comparably frequent in the two groups of patients at presentation (14/22 or 64% vs. 7/11 or 64%) and >15 years thereafter (18/22 or 82% vs. 10/11 or 91%). CONCLUSION: The precore wild type (G1896) would seem to facilitate the resolution of HBV infection, while the precore mutant (A1896) may induce severe liver diseases in patients with HBeAg-positive chronic hepatitis who have lost HBeAg from serum.     

乙肝病毒E抗原和抗体双阳性者中病毒X及前C基因变异热点研究

目的：了解乙型肝炎患者HBeAg和HBeAb双阳性状态下X区及前C区基因热点变异情况，探讨T1762与T1764及A1896热点变异与HBe转换时相的关系。方法：采用时间分辨荧光免疫分析方法定量检测乙肝5项标志物，对HBeAg/HBeAb双阳性标本采用巢式聚合酶链反应扩增，其包括X区及前C区在内的DNA片段，并对阳性的PCR产物直接标记测序，测序结果和Genbank中登录的标准序列相比较。结果：对15例HBeAg和HBeAb双阳性患者血清中HBV DNA进行了检测，阳性11例，测序结果显示，11例HBV DNA阳性者均存在T1762和A1764的突变，但仅有4例患者出现了A1896的突变。结论：在乙型肝炎HBe转换过程中均伴有BCP区T1762和A1764的突变，部分存在A1896位点的突变，T1762和A1764的突变要早于A1896的突变，而A1896的突变主要在E抗体产生过程中或产生以后。     

乙型肝炎病毒基因型与YMDD基因区序列突变及BCP突变关系探讨

目的 对湘潭地区HBV感染者的基因型、YMDD基因区序列突变及BCP区突变情况进行研究,并对三者之间的关系进行探讨.方法 针对湘潭地区952例不同类型的HBV感染者的样本同时进行基因型、YMDD基因区序列突变及BCP区突变检测,并对检测结果进行统计分析.结果 湘潭地区HBV各种基因型分布比例为:B型698例、占73.32%,C型115例、占12.08%,B、C型混合感染139例、占14.60%.YMDD基因区序列突变结果显示:YMDD野生型844例、占88.66%,其余为YMDD突变型,其中YVDD 54例、占5.67%,YIDD 53例、占5.57%,1例为YMDD与YVDD混合感染.BCP区突变结果显示:1762A/1764G(野生型)672例、占70.59%,1762T/1764A(突变型)188例、占19.75%,其余92例为1762T/1764A和1762A/1764G混合型、占9.66%.基因型、YMDD基因区序列突变及BCP区突变三者相关性分析显示:HBV B型和C型YMDD基因区序列突变率分别为10.04%、10.43%,差异无统计学意义(χ2=0.017,P＞0.05),HBV B型和C型YMDD基因区序列突变类别差异有统计学意义(χ2=4.836,P＜0.05),HBV C型YVDD突变率(9.57%)要高于B型(5.88%).HBV B型和C型BCP区突变率分别为27.36%、46.09%,差异有统计学意义(χ2=16.478,P＜0.01),C型BCP区突变率要高于B型.HBV YMDD野生型和突变型的BCP区突变率分别为2 8.67%、35.51%,差异无统计学意义(χ2=2.139,P＞0.05),但YVDD BCP区突变率(61.11%)要高于其他类别.结论 (1)湘潭地区流行的HBV基因型主要为B型和C型,其中B型为优势基因型,具有南方地区的特点.(2)拉米夫定治疗前通过HBV基因型检测来预测抗病毒应答可能并无实际意义.(3)HBV基因分型、YMDD基因区序列突变、BCP区突变检测的应用,将有助于临床上对乙肝患者的预后和转归进行正确评价,为及时合理的实施干预措施提供了重要依据.

Abstract：

Objective To investigate the relationship between HBV genotypes and YMDD motif mutations or BCP mutations in Xiangtan of Hunan Province. Methods HBV genotypes, YMDD motif mutations and BCP mutations were analyzed in 952 HBV infected patients. Results HBV genotyping showed that 698 HBV type B patients and 115 HBV type C patients accounted for 73.32% and 12.08% respectively of all the participants. The rest 139( 14.60% )were genotype B and C mixed infection( B + C ). The analysis of YMDD motif mutations showed that 844 YMDD wild-type which accounted for 88.66% of all the subjects and the remainder were YMDD mutation types, of which 54( 5.67% ) carried YVDD, 53( 5.57% ) YIDD,and 1 YVDD and YIDD mixed infection. Basic Core Promoter mutations showed that 1762A/1764G ( wild type )accounted for 70.59% and 1762T/1764A( mutant ) accounted for 19.75%. The rest 92 patients were 1762T/1764A and 1762A/1764G mixed infection. This study showed no significant difference in the rate of YMDD mutation( 10.04% vs 10.43% ,χ2 =0.017,P＞0.05 ) ,but a significant difference in the types of YMDD mutation(χ2 = 4.836, P ＜ 0.05 )between HBV types B and C. The YVDD mutation was more commonly seen in genotype C( 9.57% ) than in genotype B( 5.88% ). The BCP mutation rate showed a significant difference( 27.36% vs 46.09%, χ2 = 16.478, P ＜ 0.01 ). Genotype C was more frequent than genotype B. The BCP mutation rate showed no significant difference between YMDD Wild-type and YMDD mutation types( 28.67% vs 35.51%, χ2 = 2.139, P ＞ 0.05 ), but most of BCP mutations happened in YVDD mutant type( 61.11% ). Conclusions ( 1 ) The predominant HBV genotypes in Xiangtan were genotype B and genotype C, the major genotype was type B, which display the characteristics of epidemiology in Southern China. ( 2 ) Determination of HBV genotypes before lamivudine therapy was probably not an important pretreatment investigation to predict antiviral responses. ( 3 ) Detection of HBV genotypes, YMDD motif mutations and BCP mutations will contribute to the correct evaluation of prognosis and timely proper management of HBV patients.     

Sequential accumulation of the basal core promoter and the precore mutations in the progression of hepatitis B virus-related chronic liver disease

OBJECTIVES: Despite the pathogenic role of the basal core promoter (BCP) and the precore mutations in chronic hepatitis B virus (HBV) infection, their role in the progression of liver disease is still controversial. We analyzed whether the accumulation of these mutations might enhance the progression of HBV-related chronic liver disease. METHODS: Forty consecutive patients at each clinical status were analyzed. Clinical statuses were as follows: HBeAg-positive asymptomatic carrier (HBeAg(+) ASC) (defined as HBeAg(+), anti-HBe(-), HBV-DNA(+) by hybridization, normal ALT); inactive HBsAg carrier; chronic hepatitis B; liver cirrhosis. The genotype and the BCP/precore regions were determined by PCR using genotype specific primers and direct sequencing, respectively. RESULTS: All patients except one were infected with genotype C. The A to T mutation at nucleotide 1762 and/or G to A mutation at nucleotide 1764 were found in 30% in HBeAg(+) ASC, 65.7% in inactive HBsAg carrier, 95% in chronic hepatitis B, and 90% in liver cirrhosis (p < 0.001). The prevalence of the G to A mutation at nucleotide 1896 was 5% in HBeAg(+) ASC, 22.5% in inactive HBsAg carrier, 32.5% in chronic hepatitis B, and 50% in liver cirrhosis, respectively (p < 0.001). The T to C/A mutation at nucleotide 1753 in the BCP and G to A mutation at nucleotide 1899 in the precore were more frequent in liver cirrhosis than in the other clinical statuses (p < 0.05). CONCLUSION: Sequential accumulation of mutations in the BCP/precore has an important role in the progression of HBV-related liver disease.     

湘潭地区乙型肝炎病毒基因型与YMDD基因区序列突变及BCP区突变关系探讨

【目的】对湘潭地区HBV感染者的基因型、YMDD基因区序列突变及BCP区突变情况及关系进行探讨。【方法】对952例不同类型的HBV感染者的样本同时进行基因型、YMDD基因区序列突变及BCP区突变检测和分析。【结果】湘潭地区HBV各种基因型分布比例为：B型占73．32％,C型占12．08％,B、C型混合感染14．60％。YMDD基因区序列突变结果显示：YMDD野生型,占88．66％,其余为YMDD突变型。BCP区突变结果显示：1762A／1764G（野生型）占70．59％,1762T／1764A（突变型）占19．75％,其余为混合型。基因型、相关性分析显示：HBVB型和C型YMDD基因区序列突变率无显著性差异（P〉0．05）,序列突变类别存在显著性差异（P〈0．05）,HBVC型YVDD突变率要高于B型。C型BCP区突变率要高于B型（P〈0．01）。HBV YMDD野生型和突变型的BCP区突变率存在显著性差异（P〈0．01）,HBV YMDD突变型标本BCP区突变率与YMDD野生型相比无差异,但YVDDBCP区突变率要高于其他类别。【结论】①湘潭地区流行的HBV基因型主要为B型和C型,其中B型为优势基因型,具有南方地区的特点。②拉米夫定治疗前通过HBV基因型检测来预测抗病毒应答可能并无实际意义。③HBV基因分型、YMDD基因区序列突变、BCP区突变检测的应用,将有助于临床上对乙肝患者的预后和转归进行正确评价。     

Infectious source factors affecting the severity of sexually transmitted acute hepatitis due to hepatitis B virus genotype C

OBJECTIVE: The aim of this study was to identify clinical features and virological aspects of infectious sources that are related to the severity of sexually transmitted acute hepatitis B virus (HBV) infection in patients, especially in cases of genotype C. METHODS: Nineteen patients with acute HBV infection, 10 classified with severe acute hepatitis (SH) (prothrombin time; PT <40%) and 9 with typical acute hepatitis (AH) (PT >40%), and their infectious sources (all were sexual partners) were studied. Infectious source factors were analyzed in relation to the severity of hepatitis in the patients' partners. RESULTS: The nucleotide homology of HBV-DNA between each pair was >/=98.9%. Sixteen were infected with HBV genotype C. Among the 16 infectious sources, age, numbers with elevated alanine aminotransferase (ALT, 7/9 vs. 1/7), anti-HBe positivity (8/9 vs. 1/7) and core promoter mutations at nt 1762 (7/9 vs. 1/7), nt 1764 (8/9 vs. 1/7) and precore mutation at nt 1896 (8/9 vs. 1/7) were significantly higher in the sources of SH than in those of AH. CONCLUSION: Higher age, elevated ALT, anti-HBe positivity and core promoter/precore mutations were possible risk factors for an infectious source of the severe form of sexually transmitted acute hepatitis due to HBV genotype C.