上海地区慢性乙型肝炎患者HBV基因型特点分析

目的 探讨上海市乙型肝炎病毒(HBV)基因型分布及与HBV感染患者的临床意义.方法 选择2005年2月至2006年2月上海华山医院门诊及住院患者中HBV DNA阳性(荧光定量PCR法)的HBV感染者45例,采用S基因序列分析法检测HBV基因型,并分析相应的前-C/C基因序列特点.根据患者的HBV标志物和HBV DNA水平判断不同基因型与疾病的相关性.结果 45例HBV感染者中基因型B共15例,C型30例,无A、D、E、F、G、H基因型.15例HBV/B均为Ba亚型,其中2例的前-C/C基因与HBV/C在nt 1975～nt 2293之间发生重组.HBV/C的HBeAg阳性率显著高于HBV/B(分别为83.3%,33.3%;P＜0.05),抗-HBe阳性率则显著低(分别为53.3%,73.3%;P=0.02).2种基因型的HBV DNA水平无显著差异.结论 本次抽样检查结果中HBV基因型为B型和C型,以C型为主,未发现A、D、E、F、G、H型.HBV/C型与B型相比有较高的HBeAg阳性率和较低的抗-HBe阳性率.     

湖南省怀化市少数民族及汉族慢性乙型肝炎患者病毒基因分型及临床分析

目的 了解湖南省怀化市少数民族及汉族慢性乙型肝炎患者病毒基因型分布特点及不同基因型与临床肝病的相关性.方法 采用S基因序列分析法对湖南省怀化市111例慢性乙型肝炎患者进行乙型肝炎病毒基因分型,并分析相关流行病学、病例构成、HBV DNA载量、HBeAg阳性率及肝功能情况.结果 该地区111例慢性乙型肝炎患者HBV基因型检测到B型及C型,其中B型90例(81.08%),C型19例(17.12%),2例(1.80%)无法分型. B、C基因型分布情况:33例少数民族组患者B基因型31例(93.93%),C型2例(6.07%);76例汉族组患者B基因型59例(77.63%),C基因型17例(22.37%).C基因型患者肝硬化及肝癌构成比高于B基因型患者,HBV DNA载量、HBeAg阳性率及球蛋白水平高于B基因型,而白蛋白水平低于B基因型.结论 该地区乙型肝炎病毒基因型以B型为优势基因型,少数民族与汉族患者HBV基因型构成有显著差异,C基因型患者HBeAg血清转换率低,可能较易发生肝病进展.     

乙型肝炎病毒基因型B、C与肝细胞性肝癌临床病理的研究

目的 探讨HBV基因型B、C与肝癌临床病理方面的关联性.方法 对58名手术切除肝癌病人的血清样本进行基因型检测.结果 HBV基因型B、C的感染率分别为31%(18/58)、69%(40/58),基因型B病人肝硬化的发病率低于基因型C(33% vs 70%,P=0.01).基因型B、C多发肿瘤的发病率为28%、7.5%(P=0.04),伴有血管侵犯的发病率为33%、10%(p=0.03).结论 HBV基因型B相关性肝癌与HBV基因型C相关性肝癌相比,肝硬化发生率低,多发肿瘤及血管侵犯发病率高.造成了肝癌病人的复发及预后的差异性.     

慢性乙型肝炎病毒感染者病毒基因型分布及其与肝纤维化和肝细胞癌的关系

目的 调查浙江省杭州地区慢性乙型肝炎病毒(HBV)感染者的HBV基因型分布,并分析基因型与肝纤维化和肝细胞癌的关系.方法 回顾性分析2007年6月至2012年6月在杭州市第一人民医院就诊的190例慢性HBV感染者的血清学、病毒学指标和临床病理学资料.190例患者根据病理及相关检测分为慢性乙型肝炎(CHB)组(62例)、肝硬化组(60例)和肝细胞癌组(68例).HBV基因型测定采用多重PCR扩增,基因亚型测定采用PCR扩增结合限制性片段长度多态性(RFLP)方法.采用SPSS 11.0软件进行统计学分析.结果 190例慢性HBV感染者中,B基因型感染61例(32.1％),C基因型感染126例(66.3％),3例为B、C基因混合型感染.其中,B基因型全部为B2亚型,C基因型中C2亚型占绝对优势(97.6％,123/126).B基因型在CHB组的比例(46.8％,29/62)高于肝硬化组(20.0％,12/60)和肝细胞癌组(29.4％,20/68)(x2=8.73和4.16,P＜0.01或＜0.05);C基因型在肝硬化组和肝细胞癌组的比例高于CHB组(x2=9.54和4.17,P＜0.01或＜0.05).三组患者中感染C2基因亚型的血清透明质酸(HA)水平高于感染B2基因亚型的患者(t=2.685,2.433和2.015,P＜0.01或＜0.05).CHB患者中感染C2基因亚型者比感染B2基因亚型者有更高的肝纤维化分期(x2=6.726,P=0.010),而肝脏炎症分级差异无统计学意义(x2=0.601,P＞0.05).肝细胞癌患者中,感染B2基因亚型者肿瘤直径≥5 cm的比例更高(x2=7.231,P＜0.01),感染C2基因型者伴肝硬化更常见(x2 =4.910,P＜0.05).结论 浙江省杭州地区CHB患者以C2和B2基因亚型为主.感染C2基因亚型的患者可能更易发展为严重肝纤维化,而感染B2基因亚型的患者和大肝癌相关.     

HBV感染者HBsAg和HBsAb同时阳性的血清学异常模式的研究

目的：分析HBsAg和HBsAb同时阳性的慢性HBV感染者的血清学模式,分析病毒Pre-S/S区基因序列变异或缺失情况对其进行基因分型,并探讨其临床意义。方法采用酶联免疫分析法筛选出HBsAg和HBsAb同时阳性的慢性HBV感染者共100例,采用化学发光微粒子免疫分析确认,用实时荧光定量聚合酶链反应（PCR）检测其HBV DNA含量,其中HBV DNA阳性者60例, HBV DNA阴性者40例。将60例HBsAg和HBsAb同时阳性的慢性HBV感染者作为实验组,并选取60例HBsAg（＋）HBsAb（-）的慢性乙型肝炎患者作为对照组。采用PCR法体外扩增两组患者HBV Pre-S/S基因序列并测序分析,根据测序结果对患者的基因型进行分型,比较两组Pre-S/S基因变异情况,结合临床资料探讨其临床意义。结果实验组患者中B基因型19例、C基因型41例,对照组患者中B基因型18例、C基因型42例。实验组B基因型患者的年龄[（50.0＆#177;16.3）岁]大于C基因型[（34.0＆#177;13.4）岁],差异具有统计学意义（F=31.6,P=0.0432）。实验组B基因型和C基因型的S区氨基酸突变率分别为10.8%和21.6%,差异具有统计学意义（F=24.31,P=0.046）。同样为C基因型的两组患者,实验组S区氨基酸突变为41.6%,显著大于对照组的氨基酸突变率（3.2%）,差异具有统计学意义（F=85.68,P=0.006）。结论 HBsAg（＋）且HBsAb（＋）并伴有HBeAg（＋）的患者血清中HBV DNA的阳性率显著增高。HBsAg和HBsAb同时阳性的现象与pre-S/S区基因突变具有显著关性,且C基因型的突变率高于B基因型患者的突变率。     

替诺福韦酯对四川地区妊娠中期高HBV载量慢性乙型肝炎孕妇母婴阻断的疗效

目的探讨替诺福韦酯（TDF）在四川地区感染高载量不同基因型乙型肝炎病毒（HBV）妊娠中期孕妇中阻断HBV母婴传播的疗效。 方法选择2016年8月至2019年8月成都市公共卫生临床医疗中心收治的高HBV载量乙型肝炎孕妇共258例，根据患者意愿分为观察组（156例）和对照组（102例），观察组孕妇于妊娠第24周开始口服TDF至分娩当日停药，对照组孕妇不予抗病毒治疗。两组孕妇所生婴儿均接受规范的乙型肝炎免疫接种，对抗病毒治疗后孕妇及婴儿的安全性及母婴阻断效果进行比较。 结果258例孕妇中HBV基因B型213例（82.5%），C型45例（17.5%），差异有显著统计学意义（χ² = 14.616、P < 0.001）。无B/C混合基因型和其他基因型检出。基因B型与基因C型HBV DNA基线载量差异无统计学意义（t = 0.752、P = 0.458）。两组患者的新生儿早产发生率（χ² = 0.018、P = 0.904）、剖宫产率（χ² = 0.038、P = 0.813）和产后24 h出血量（t = 0.153、P = 0.703）差异均无统计学意义。观察组患者分娩时HBV DNA水平较抗病毒治疗前显著降低（t = 19.67、P = 0.032），随访至产后7个月，观察组婴儿HBsAg阳性者2例（阳性率为1.28%），HBeAg、HBV DNA均为阴性；对照组婴儿HBsAg阳性者9例（阳性率为8.82%），其中HBeAg阳性者6例（阳性率为5.88%），HBV DNA阳性者6例（阳性率为5.88%）。两组婴儿HBsAg阳性率差异有统计学意义（χ² = 4.956、P = 0.038）。观察组HBV基因B型及C型在抗病毒治疗后HBV DNA载量均显著下降，差异无统计学意义（t = 1.043、P = 0.491）。发生母婴传播的11例患者中，8例为基因B型，3例为基因C型，两种基因型母婴传播发生率差异有统计学意义（χ² = 4.527、P = 0.045）。观察组中3例孕妇出现轻微头晕、乏力，1例孕妇出现轻微恶心、食欲下降，不良反应发生率为2.6%（4/156）。治疗期间无血磷和血肌酐异常。两组患者新生儿头围、身长、体质量差异均无统计学意义（P均> 0.05）。 结论四川地区乙型肝炎孕妇HBV基因型以B型为主，TDF用于高HBV载量的妊娠中期乙型肝炎孕妇安全性好，能有效阻断HBV母婴传播。     

HCV合并HBV感染者血清学指标的相关价值研究

目的探讨HCV合并HBV感染者的血清学指标,分析混合感染后的基因型情况并探讨其临床意义。 方法采用ELISA方法对431例丙型肝炎患者进行抗-HCV以及乙型肝炎病毒抗原-抗体的血清学检测,采用化学发光微粒子免疫分析确认,其中HCV感染合并HBV感染者60例作为试验组,HCV感染者60例为对照组。采用实时荧光定量聚合酶链反应（PCR）对60例HCV合并HBV感染的患者血清进行HCV RNA和HBV DNA载量检测,并对HCV和HBV进行基因分型及检测生化指标。 结果试验组与对照组患者病毒载量高于1 × 10⁵拷贝/ml的感染者分别为68.33%（41/60）和31.67%（19/60）,差异具有统计学意义（F = 35.35、P = 0.0403）。试验组患者HCV的3个亚型分别为1b 71.67%（43/60）、2a 26.67%（16/60）和6a 1.67%（1/60）,HBV分型C、B基因型分别为83.33%（50/60）和41.67%（25/60）,差异具有统计学意义（F = 38.15、P = 0.0326）。试验组与对照组的转氨酶升高的阳性率分别为56.67%（34/60）和25.00%（15/60）,差异具有统计学意义（F = 40.65,P = 0.0214）。 结论HCV合并HBV感染后HBV基因型以C型为主,感染后抗-HCV水平不受影响。感染的HBV受HCV的抑制。HCV合并HBV感染者可能会增加肝癌发生的风险。     

乙型肝炎病毒基因型及S、P基因变异与肝移植术后乙型肝炎病毒感染的关系

目的 探讨乙型肝炎病毒(HBV)基因型和S、P基因变异与肝移植术后HBV再感染的关系.方法 因乙型肝炎相关终末期肝病接受肝移植,术后随访1.5～3年,发生HBV再感染者14例(再感染组),移植前服用拉米夫定,移植后采用拉米夫定和抗乙型肝炎球蛋白(HBIG)预防HBV再感染.采用聚合酶链反应测定血清中HBV DNA水平,基因测序法分析HBV基因型、S基因及P基因变异,微粒子捕捉酶免法检测血清HBIG浓度.随机选取同期因乙型肝炎相关终末期肝病接受肝移植而未发生HBV再感染者20例为对照.结果 再感染组移植前血清HBV DNA≥103拷贝/ml者占71.4%,明显高于对照组的30%(P<0.05).再感染组移植前HBV基因型有B型(2例)和C型(12例),移植后基因型不变;对照组B型11例,C型9例.再感染组3例术前发生拉米夫定耐药位点变异者,9例C型者在P区拉米夫定耐药位点变异以外发生多位点氨基酸变异,且变异位点差异较大.再感染组50%的患者HBIG浓度为0,其S区"a-决定簇"的基因均发生变异.结论 乙型肝炎相关终末期肝病患者肝移植后的HBV再感染与HBV基因型有关,C基因型者更易发生HBV再感染;再感染可能与P基因区存在多位点变异及S区的"a-决定簇"基因变异密切相关.     

乙型肝炎患者HBV基因型与核苷(酸)类似物耐药变异的关系

目的 探讨乙型肝炎病毒(HBV)基因型与核苷(酸)类似物抗病毒治疗过程中耐药变异发生的关系.方法 采用荧光定量聚合酶链反应(PCR)DNA测序方法,进行HBV基因分型,同时检测拉米夫定、阿德福韦酯和恩替卡韦特异耐药变异位点.结果 在湖南128例拉米夫定治疗患者中,HBV基因型B为107例,占83.6%;基因型C为21例,占16.4%,未发现基因型A、D、E、F、G、H型.总的耐药变异发生率48.4%(62/128),发生在12、24和36个月者分别为4.7%(6/128)、16.4%(21/128)、42.9%(55/128),随治疗时间延长,变异发生率增加(P＜0.01).基因型B、C感染发生YMDD突变率分别为49.5%和42.9%,无显著差异(P＞0.05),但YMDD变异类型在两基因型中不同,基因型B、C发生YVDD变异分别为64.2%(34/53)和0.0%(P＜0.01),YIDD变异分别为22.6%(12/53)和88.9%(8/9),P＜0.01.阿德福韦酯和恩替卡韦治疗一年尚未检测到耐药变异,45例经阿德福韦酯治疗24月时变异发生率为4.4%(2/45),变异率在B、C基因型患者中分别为0% (0/38)和28.6% (2/7),变异型均为N236T.结论 基因型B为湖南省的优势基因型,HBV基因型对核苷(酸)类似物抗病毒治疗反应有一定的影响.     

乙型肝炎病毒基因分型与拉米夫定临床应用反应

目的了解常州地区乙型肝炎病毒(HBV)基因型分布特征,探讨基因型与肝功能损害、病毒复制水平及其与拉米夫定疗效关系.方法 76例慢性乙型病毒性肝炎患者每天口服拉米夫定100mg治疗,并于治疗4～6周时测定不同基因型患者的丙氨酸转氨酶(ALT)和HBV DNA,治疗48周后测定HBV DNA反跳和YMDD变异.采用巢式聚合酶链反应(nest PCR)法扩增HBV S基因区,以4色荧光标记PCR产物末端,在以毛细管高压电泳为核心技术的核酸序列分析仪上自动测序,将测序结果与基因库中登录的标准基因型序列相比较.结果 76例慢性乙型肝炎患者血清HBV DNA基因分型示:B型株感染26例(34.2%),C型株感染50例(65.8%).B和C基因型患者ALT值分别为(246.3&#177;138.8)U和(283.7&#177;125.6)U,(t=0.335,P&gt;0.05),HBV DNA含量分别为107.124&#177;101.49和107.189&#177;101.56拷贝/ml(t=0.138, P&gt;0.05),HBeAg阳性数分别为20例和41例(χ2=0.159,P&gt;0.05).拉米夫定治疗4～6周后,B基因型和C基因型患者ALT、HBV-DNA(阴转)、HBV DNA(拷贝/ml)均呈良好恢复状态,两组间差异无显著性.治疗48周后,HBV DNA反跳者B基因型20例,C基因型16例(χ2=13.49,P&lt;0.001).结论常州地区HBV DNA基因型以单一B或C型为主;不同基因型患者ALT水平、病毒复制水平以及HBeAg表达水平差异均无显著性,拉米夫定对C基因型患者的疗效优于B基因型.     

Chronic hepatitis B virus infection

Chronic hepatitis B virus infection affects approximately 350 million people worldwide and 1.1 million in Romania. Despite the tremendous progress in the management of virus B infection, the treatment of chronic hepatitis B remain difficult and often disappointing. The aim of treatment is sustained suppression of HBV replication and remission of liver disease. Treatment is not indicated in immune tolerance phase or in the inactive carrier state, but it is necessary in immune clearance phase, after 3-6 months of surveillance. Two antiviral drugs are accepted: alpha-interferon and lamivudine. The results of both treatments are far of being perfect; new, more potent antiviral drugs are required.     

慢性乙型肝炎患者病毒准种的研究进展

由于乙型肝炎病毒（HBV）的逆转录酶缺乏校正活性,在病毒复制过程中产生大量核苷酸错配,故HBV在宿主体内表现为大量在遗传学上高度相关而又有差别的病毒群体,这一群体称为准种,宿主体内的病毒准种在宿主免疫压力和药物的选择压力下不断发生动态变化,因此HBV准种变化在慢性乙型肝炎的抗病毒治疗、耐药检测以及预后等方面均有重要作用。本文对HBV准种变化与慢性乙型肝炎进展的关系作一综述。     

Adefovir treatment in posttransplant hepatitis B virus infection resistant to lamivudine plus hepatitis B virus immunoglobulin

Failure of prophylaxis for hepatitis B virus (HBV) recurrence in liver transplant patients with HBV immunoglobulin (HBIG) or lamivudine or both can be associated with rapid development of liver failure. Some of these patients develop a devastating clinicopathological state characterized by jaundice and rapidly progressive liver failure or fibrosing cholestatic hepatitis. We present two liver transplant recipients who experienced HBV recurrence while they were under lamivudine and HBIG prophylaxis. One of them had finding of severe HBV infection; the other, fibrosing cholestatic hepatitis. After commencing adefovir dipivoxil both patients showed improvements in clinical status and laboratory data. At month 4 of treatment, HBV DNA values became negative and liver function tests almost normalized. In addition, in one case showed HBs ag/anti-HBs seroconversion. When failure of prophylaxis with lamivudine and HBIG occurs, adefovir dipivoxil should be considered to be a safe and effective choice for recurrent HBV infections in liver transplant patients.     

Preliminary results: Outcome of liver transplantation for hepatitis B virus varies by hepatitis B virus genotype

Hepatitis B virus (HBV) is a leading cause of liver failure throughout the world. HBV has seven different genotypes based on variations within the viral nucleotide sequence. Initially, patients who underwent liver transplantation for HBV had high recurrence rates and poor survival. Recently, improved outcomes have been reported when patients are administered hepatitis B immunoglobulin (HBIg) infusions to maintain high serum hepatitis B surface antibody titers after transplantation. Unfortunately, recurrence rates are still high in patients with active pretransplant HBV replication. The aims of this study are to evaluate the impact of HBV genotype on pretransplantation HBV replication and posttransplantation HBV recurrence rate, morbidity, and mortality. Sera from 22 patients who underwent transplantation for HBV at our center were tested for HBV genotype by an enzyme-linked immunosorbent assay technique using monoclonal antibodies to the pre-S2 region. All patients were administered HBIg after transplantation; 5 patients were administered both lamivudine and HBIg. HBV genotypes were distributed as follows: genotype A (10 patients), genotype C (6 patients), genotype D (5 patients), and genotype E (1 patient). Pretransplantation HBV replication was most common with genotype A (80%), whereas less so with genotypes C (33%) and D (40%). Nine patients (41%) developed recurrent HBV infection: genotype A (2 patients; 20%), genotype C (3 patients; 50%), and genotype D (4 patients; 80%). Mortality was greatest with genotype D (40%). Our data suggest that patients with genotype A have the lowest risk for HBV recurrence despite having the highest rate of pretransplantation HBV viral replication. Patients with genotype D appear to have the highest risk for HBV recurrence and mortality. Additional larger multicenter studies are needed to confirm these findings. (Liver Transpl 2002;8:550-555.)     

Mutation analysis of hepatitis B virus X gene in hepatitis B virus-associated glomerulonephritis

Objective To determine whether mutation of Hepatitis B virus (HBV) X gene is associated with hepatitis B virus-associated glomerulonephritis (HBV-GN). Methods The venous blood was collected from 50 patients with HBV-GN and 60 patients with asymptomatic HBV carriers (control group). Serum HBV DNA was extracted to determine the serum titer of HBV-DNA and then polymerase chain reaction (PCR) was used to detect the HBV X gene mutation. Results (1)There were not statistical significance between age and gender in HBV-GN group and control group (P＞0.05). There were not statistical significance of serum replication level of HBV DNA in HBV-GN with X gene mutation and control group (P＞0.05). Urine protein excretion in HBV-GN group with or without X gene mutation was found with statistical significance (P＜0.05). (2)Nucleotide mutations [84%(42/50)] resulted in amino acid substitution in HBV-GN. Nucleotide mutations changed in trans-function control region of X gene, including position nt1653, nt1726, nt1727, nt1730, nt1753, nt1762 and nt1764. (3)Nucleotide mutations [8%(5/60)] resulted in amino acid substitution in control group. Nucleotide mutations changed in position nt1632 and nt1635, located in non-functional region. Conclusions HBV X gene mutations and the subsequent amino acid substitutions are found in HBV-GN. The urine protein excretion level increases in patients with X mutation, suggesting that these mutations may play an important role in the pathogenesis of HBV-GN.     

The extrahepatic manifestations of hepatitis B virus

Hepatitis B Virus (HBV) leads to a number of hepatic complications, from acute to chronic hepatitis, cirrhosis and hepatocellular carcinoma, is a well-established fact. Upcoming clinical research, over the years, associates numerous extrahepatic manifestations during the acute and chronic episodes of hepatitis B with significant morbidity and mortality. A causal relationship between HBV and serious autoimmune disorders has also been observed among certain susceptible vaccine recipients in a defined temporal period following immunization. The cause of these extrahepatic manifestations is generally believed to be immune mediated. The most commonly described include skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, and papular acrodermatitis etc. The serum-sickness like "arthritis-dermatitis" prodrome has also been observed in approximately one-third of patients acquiring HBV infections. Skin manifestations of HBV infection typically present as palpable purpura reported to be caused by chronic HBV, although this association remains controversial. To consider the relationship between HBV and other clinically significant disorders as well as serious autoimmune disorders among certain vaccine recipients is the topic of this review. Variable factors that influence extrahepatic manifestation are discussed, including possible synergy between hepatitis B virus and the immune system.     

维持性血液透析患者感染乙型和丙型肝炎的分析

目的为了评价血液透析（血透）患者乙型和丙型肝炎（HBV、HCV）感染状态及对临床情况和肝功能的影响。方法对62例血透患者应用ELISA法和RT-PCR法检测抗-HCV和HCVRNA，采用斑点杂交法和固相放免法检测HBV标志，并检测肝功能和血浆蛋白电泳。结果62例患者中，抗-HCVIgM阳性27例（43．6％），抗-HCVIgG阳性29例（46．8％），HCVRNA阳性34例（54．8％），三项任一项阳性37例（59．7％），5例（8．1％）HBsAg阳性，其中HBeAg和HBVDNA阳性3例。结论向透患者中HCV感染严重，临床情况及预后差，检测血浆蛋白和电泳较肝功能酶学能更好地作为肝炎诊断和反映病情的指标。