上转发光免疫层析法定量检测乙型肝炎病毒外膜大蛋白的临床价值研究

目的评价上转发光免疫层析法定量检测乙型肝炎病毒外膜大蛋白（HBV—LP）在乙型肝炎患者中的应用价值。方法利用一种新的基于上转发光法的免疫层析检测技术（UPT）检测500份乙肝病毒感染患者血清样品HBV．LP含量,并采用实时荧光定量PCR法检测HBVDNA;化学发光法检测乙肝五项指标。结果500例乙肝病毒感染患者HBV-LP与HBVDNA阳性率分别为58．0％和42．2％,两者间差异有统计学意义（P〈0．01）,其中215份HBeAg阴性患者血清中,HBVDNA与HBV—LP的阳性率分别为29．3％和37．2％,两者差异无统计学意义（P〉0．05）;HBeAg阳性检出率为57．0％,与HBVDNA阳性检出率差异有统计学意义（P〈0．01）。结论上转发光免疫层析法检测乙肝病毒外膜大蛋白对HBeAg阴性和HBVDNA低拷贝患者体内病毒复制及预后评价有重要价值,联合检测HBVDNA、HBV—LP和HBeAg有利于乙肝病毒复制水平的判断和抗病毒治疗终点的确定。     

烟台地区献血人群感染乙肝病毒血清学标志的表现模式

目的 探讨献血员感染乙肝病毒(HBV)血清学标志的表现模式.方法 利用酶联免疫吸附试验( EUSA)以AlisA多功能全自动酶联免疫快速分析仪进行检测.荧光定量聚合酶链式反应(PCR)检测HBVDNA.设定HBV血清学标记检测项目序号,并以出现阳性项目的序号为该模式的代码.结果 139份乙肝表面抗原(HBsAg)灰区及阳性献血者样本乙肝血清学标记模式有28种,以14567,0,02,145,13567模式为主,占66,91％;另可见15种特殊模式,其中11种为HBsAg灰区表现模式,部分献血员HBsAg灰区人群HBVDNA阳性;检测出44例HBVDNA阳性样本(31.65％),其血清学标记模式有16种.结论 献血员感染HBV血清免疫学标记的模式较为复杂,应重视对献血员乙肝表面抗原(HBsAg)灰区人群的研究.     

孕妇注射乙肝免疫球蛋白阻断HBV宫内传播的研究

目的 :研究乙型肝炎免疫球蛋白 (HBIG)对HBsAg阳性孕妇的乙肝病毒 (HBV)宫内阻断作用及孕妇血清中HBVDNA水平与宫内感染的关系。方法 :HBIG组 5 6例 ,孕 2 8周起肌注HBIG ,每 4周一次至分娩 ;对照组 5 2例 ,未予用药。两组孕妇均于孕 2 8周、分娩前 ,其新生儿于生后 2 4小时内免疫接种前抽静脉血检测HBsAg ,HBeAg及HBVDNA定量。结果 :HBIG组孕妇HBVDNA水平显著下降 (P <0 .0 5 ) ,其新生儿宫内感染率明显低于对照组 (分别为 16 .1%和 32 .7% ) ,P <0 .0 5。胎儿宫内感染率随着孕妇血清中HBVDNA含量增加而呈现增高趋势 (P <0 .0 5 )。两组孕妇及其新生儿未发现有不良反应。结论 :携带HBV孕妇产前多次注射HBIG可有效减少HBV宫内感染发生率 ;孕妇血清HBVDNA水平增高是胎儿发生HBV宫内感染的重要因素之一     

干扰素治疗慢性乙型肝炎过程中HBsAg发生阴转的病例分析

目的通过分析聚乙二醇干扰素α-2a治疗慢性乙型肝炎（CHB）患者发生HBsAg阴转病例的临床及实验室指标的特点,探讨影响HBsAg阴转的相关因素。方法选择中山大学附属第三医院3年间收治并给予聚乙二醇干扰素α-2a治疗的CHB患者61例,对其中发生HBsAg阴转的病例进行临床、实验室指标等分析。结果经聚乙二醇干扰素α-2a治疗的61例患者中,5例发生HBsAg阴转（占8.2%）,56例未阴转（占91.8%）;HBsAg阴转组平均年龄（26.5±7.5）岁,HBsAg阳性史平均（4.3±1.7）年;HBsAg未阴转组平均年龄（35.7±8.3）岁,HBsAg阳性史平均（6.7±2.8）年。阴转组基因分型均为B型,HBVDNA滴度治疗前较未阴转组低,未合并其他肝炎病毒感染,无乙肝家族史,既往未用过抗病毒药物治疗,治疗前均为HBeAg阳性的乙型肝炎。结论聚乙二醇干扰素α-2a抗病毒治疗CHB可以获得HBsAg的阴转,HBsAg的阴转可能与患者的基因分型、HBV DNA滴度、年龄、HBsAg阳性史、家族史等因素有关。     

免疫干预后母婴传播乙肝病毒标记物分析

目的：分析免疫干预后乙肝阳性产妇与新生儿脐带血标本乙肝标志物,评价其临床价值。方法：对我院228例经免疫预防乙肝阳性产妇所生新生儿脐带血资料进行回顾性分析,比较产妇与其新生儿乙肝标志物模式。结果：新生儿脐带血HBsAg和（或）HBeAg阳性23例,宫内感染率10.1%;其中双阳组产妇61例,所娩新生儿脐带血HBsAg和（或）HBeAg阳性21例,宫内感染率34.4%;单阳组167例,所娩新生儿脐带血HBsAg阳性2例,宫内感染率1.2%,两组宫内感染发生率有显著性差异（P〈0.05）。结论：产妇和新生儿HBeAg阳性是宫内感染和HBV感染慢性化的危险因素;对产前孕妇、出身后新生儿进行免疫干预是阻断HBV母婴传播的有效手段。     

检测乙型肝炎病毒表面抗原大蛋白的临床意义

目的检测乙肝患者血清中乙肝两对半（HBVM）、乙型肝炎病毒表面抗原大蛋白（HBV—LP）以及HBVDNA，比较在不同乙肝两对半模式的患者中HBV．LP与HBVDNA的检出率，探讨乙型肝炎病毒表面抗原大蛋白（HBV—LP）用于乙肝患者临床诊断的意义。方法采用酶联免疫吸附实验（ELISA）检测HBV．LP和乙肝两对半，采用荧光定量PCR方法对患者HBVDNA进行检测。结果（1）相同乙肝模式患者血清中HBV．LP与HBVDNA检出率差异无统计学意义；（2）143例小三阳乙肝患者血清中HBV．LP与HBVDNA阳性率差异无统计学意义，二者的检出一致率为82．52％[（65＋53）／143]；（3）HBV—LP吸光度（A值）与HBVDNA呈正相关关系（r=0．983）。结论乙型肝炎病毒表面抗原大蛋白与HBVDNA有良好的正相关关系，在HBeAg阴性的乙肝患者中乙肝病毒表面抗原大蛋白（HBV—LP）与HBVDNA有较高检出一致率，HBV—LP用于临床反映乙肝病毒复制水平，特别是HBeAg阴性乙肝患者体内病毒复制情况有重要的意义。     

拉米夫定在肝脏移植患者乙肝病毒再感染预防与治疗中的应用—第36届欧洲肝病年会巡礼

肝脏移植后有各种类型的合并症。由于接受肝脏移植的患者有相当比例是慢性乙肝病毒（HBV）感染引起的终末性肝病患者，而且肝脏移植供体也包括相当数量的HBV标志阳性的人群，因此肝脏移植后有再发HBV感染的问题。肝脏供体的HBV标志类型、HBVDNA是否已经发生变异、以及是否经过合适的预防性抗病毒治疗，都是影响肝脏移植患者发生HBV再感染的重要因素。拉米夫定，以及拉米夫定联合小剂量乙肝病毒高效价免疫球蛋白（HBIG）是预防肝脏移植后再发HBV感染的有效手段。尽管拉米夫定对于肝脏移植后再发HBV感染的抗病毒疗效不满意，且易出现HBV DNA的YMDD基因变异，但探索拉米夫定为主的联合抗HBV治疗方案可能是较好的解决方案。     

乙肝核心抗体阳性供肝在肝移植中的应用

背景：现已经证实使用anti-HBc(+)供肝会使移植后乙肝复发的风险,但anti-HBc(+)供肝的应用明显缓解了供肝的相对匮乏。 目的：分析应用anti-HBc(+)供肝移植后乙肝复发风险及有效的预防措施。 方法：应用计算机检PubMed数据库中1994-01/2009-12关于anti-HBc(+)供肝文章,在标题和摘要中以“Hepatitis B core antibody; donor;liver transplantation”为检索词进行检索。选择与anti-HBc供肝相关文章。初检得到109篇文献,根据纳入标准选择48篇文章进行综述。 结果与结论：HBsAg(+)患者接受anti-HBc(+)供肝移植术后乙肝复发率为11%,生存率为67%~100%,与HBsAg(+)受者接受anti-HBc(-)供肝相似。HBsAg(-)受者接受anti-HBc(+)供肝总体感染率为19%,其中未感染过乙肝受者移植术后乙肝感染率为48%,感染过乙肝受者后感染率为15%。未感染乙肝与感染过乙肝受者移植后采取有效预防措施后感染率分别为3%,12%。采用HBIG、拉米夫定、联合用药的移植后感染率分别为19%,2.6%,2.8%。提示,采用anti-HBc(+)供肝做为供体是安全的,尤其是用在HBsAg(+)、anti-HBc(+)、anti-HBs(+)受者。而HBsAg(-)受者移植后接受拉米夫定可以有效复发乙肝感染。     

异基因造血干细胞移植后乙型肝炎病毒感染2例临床干预并文献复习

目的加强对造血干细胞移植中HBV感染的重视,注重早期干预,提高移植成功率。方法回顾性分析97例异基因造血干细胞移植患儿的临床资料,通过对2例HBV感染的诊治体会结合文献复习。结果2001年5月至2008年5月在上海交通大学附属上海儿童医学中心接受异基因造血于细胞移植的97例患儿中,2例分别在移植后41d（病例1）、15个月（病例2）发生HBV感染。病例1移植前肝功能正常,乙肝二对半检查阴性,回顾性分析发现该患儿移植时HBV正处于潜伏状态（HBV—DNA1．17×10^6copies·mL^-1）。该患儿乙肝来势凶猛,移植后41～43d出现巩膜明显黄染并伴大量腹水,移植后46d迅速发展至肝、肾功能衰竭,出现少尿,凝血酶原时间38．4S,部分凝血酶原时间〉120S,凝血酶时间〉100s,Cr251μmol·L^-1,ALT3195U·L^-1,血清总胆红素7mg·L^-1,直接鹏红素2．8mg·L^-1,HBV—DNA1,08×10^3copies·mL^-1,经拉米夫定等积极治疗2周后好转。移植后130d随着移植物抗宿主病（GVHD）的复燃和免疫抑制药物的加强应用,HBV再度活跃,HBV—DNA从原已控制的3．50×10^4copies·mL^-1逐升至2．05×10^6copies·mL^-1,移植后315d出现HBVYMDD（＋）变异株,遂予阿德福韦酯联合治疗至今（移植后3．5年）,目前肝、肾功能正常。病例2白血病起病初及干细胞移植前均示HBs-Ab（＋）、HBc—Ab（＋）、HBe—Ab（＋）,A¨和HBV—DNA正常,移植后12个月发生慢性广泛性GVHD,加强抗排异治疗后于移植后15个月复查发现：ALT168U·L^-1,HBV-DNA升至5×10^8copies·mL^-1,出现HBs-Ag（＋）和HBe-Ag（＋）。予拉米夫定治疗至移植后4．5年,目前ALT40～80U·L^-1,HBV—DNA1×10^3～1×10^4copies·mL^-1。结论乙肝在移植患儿巾并不少见,长期的免疫抑制治疗常使病情反复,加强病毒监测、重视早期干预至关重要;移植前HBVDNA检测有助于发现潜伏期患儿;HBs—Ab（＋）、HBe—Ab（＋）和HBc—Ab（＋）患儿在强烈免疫抑制下仍有HBV复燃的风险。     

阻断乙型肝炎病毒父婴传播的研究

目的探讨阻断乙型肝炎（乙肝）病毒父婴垂直传播的有效方法。方法将在北京市海淀区妇幼保健院乙肝母婴阻断门诊就诊的配偶为HBV携带者的孕妇共例61例作为观察对象,22例配偶为乙肝表面抗原和乙肝e抗原双阳性及乙肝病毒脱氧核糖核酸阳性。其中28例孕妇也为乙肝病毒携带者,仅1例孕妇为HBsAg和HBeAg双阳性。对33例本人未检出HBV抗原的孕妇检测乙肝表面抗体定量,对定量较低或阴性的孕妇在孕前或孕期接种国产（基因重组酵母）乙肝疫苗10μg,根据定量接种1—2次。对孕妇也为HBV携带者和孕妇在孕末期前检验血中尚未达到高滴定度保护性抗体乙肝表面抗体者,在孕末期28、32、36w各肌肉注射乙肝免疫球蛋白400IU。观察新生儿生后12h内静脉血乙肝表面抗原和乙肝e抗原及乙肝表面抗体定性,采用酶联免疫法定性测定。结果所有观察新生儿61例生后12h内静脉血乙肝表面抗原和乙肝e抗原均为阴性,以后3、6、12个月复查乙肝表面抗原和乙肝e抗原未发现阳转者。33例母亲未检出HBV的新生儿生后12h内静脉血乙肝保护性抗体乙肝表面抗体均为阳性,28例母亲也为乙肝病毒携带者的新生儿乙肝表面抗体均为阴性。结论对配偶为乙肝病毒携带者的孕妇在孕前或孕期接种乙肝疫苗;对孕妇也为HBV携带者或孕妇在孕末期前检验血中尚未达到高滴定度保护性抗体乙肝表面抗体者,在孕末期肌肉注射较大剂量乙肝免疫球蛋白的措施可基本阻断乙肝病毒父婴垂直传播。     

Development of antibodies to hepatitis B virus surface antigen in bone marrow transplant recipient following treatment with peripheral blood lymphocytes from immunized donors.

Bone marrow transplantation (BMT) recipients are immunosuppressed and are at risk for contracting severe infections. Recently, adoptive transfer of immunity against hepatitis B virus (HBV) was documented in BMT recipients receiving bone marrow from 'naturally' HBV-infected individuals who recovered spontaneously, or those transplanted with bone marrow cells obtained from actively immunized donors. Furthermore, reconstitution of the immune system in a BMT recipient who was a hepatitis surface antigen (HBsAg)+/HBV DNA+ carrier with HBV immune bone marrow cells led to clearance of the replicating virus, presumably through adoptive cell-mediated immunotherapy. We report three cases of induction of immunity to HBV by selective adoptive transfer by i.v. injection of peripheral blood lymphocytes (PBL) obtained from BMT donors who were actively immunized against HBV after harvesting of bone marrow. All three BMT recipients developed anti-HBs antibodies. In one BMT case in whom antibodies to HBsAg developed following adoptive transfer of immune PBL, a mild booster effect was documented in the BMT recipient upon immunization with a recombinant hepatitis B vaccine. The two remaining patients lost their antibodies to HBsAg in association with relapse of leukaemia. This immune manipulation may open the door to evaluation of adoptive transfer of immunity to HBV through selective transplantation of HBV immune lymphocytes in selected patients such as those with persistent HBV infection, as well as liver transplant recipients who require protection of the graft against HBV re-infection.     

Lamivudine prophylaxis and treatment of hepatitis B Virus-exposed recipients receiving reduced intensity conditioning hematopoietic stem cell transplants with alemtuzumab

Individuals with past exposure to hepatitis B virus (HBV) may reactivate HBV following bone marrow transplantation. Alemtuzumab (CAMPATH)-based reduced intensity conditioning bone marrow transplantation has been associated with a high incidence of viral infections. Lamivudine prophylaxis for HBV should be instituted in this setting. The management of 240 CAMPATH-based reduced intensity conditioning bone marrow transplantation, carried out over an 8-year period at Kings College Hospital, was reviewed. Hepatitis B core total antibody (anti-HBc) testing identified recipients and donors with previous HBV exposure. Fifteen donor-recipient pairs were identified as being at risk of HBV reactivation. Eight recipients of anti-HBc negative donors were HBsAg negative, anti-HBc positive pre-transplantation. Five anti-HBc negative recipients received transplants from HBsAg negative, anti-HBc positive donors. Two HBV carrier recipients had one anti-HBc negative and one positive donor, respectively. Pre-transplant lamivudine prophylaxis was given to 8/10 (80%) anti-HBc positive recipients. Although HBsAg and HBV DNA were detected 4 months after bone marrow transplantation in one patient who did not receive prophylaxis, a good antiviral response was documented on starting lamivudine. The two HBV carrier recipients had stopped lamivudine at 8 and 31 months post-bone marrow transplantation, respectively, and died of liver failure with a sharp rise in HBV DNA levels. The five anti-HBc negative recipients with anti-HBc positive donors remained HBsAg and HBV DNA negative. Although lamivudine prophylaxis prevented HBV reactivation, it is unclear at what stage post-transplantation prophylaxis can be discontinued. Close monitoring of liver function tests (LFTs), HBsAg, and HBV DNA must be undertaken even after stopping antiviral prophylaxis.     

De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome

De novo infection of hepatitis B virus (HBV) occurs after liver transplantation from donors with HBV markers that suggest past infection. In the present study, the complete nucleotide sequences of HBV derived from a donor and recipients were determined to determine the clinical and virological characteristics. A total of 57 donor-recipient pairs, which underwent living-related orthotopic liver transplantation, were enrolled in the present study; all were negative for HBsAg before transplantation. HBV DNA was tested in serum, liver tissue, and peripheral blood mononuclear cells (PBMCs) by the polymerase chain reaction (PCR). The nucleotide sequence of HBV was determined based on PCR products and the phylogenetic analysis. De novo infection of HBV was found in 3 of the 57 recipients. Anti-HBc was positive in all donors of 3 recipients with the de novo infection but was positive only in 4 donors of the remaining 54 recipients (P=0.001). HBV DNA was detected in the liver but not in the serum or PBMCs in donor 3 whose recipient developed de novo HBV infection. The nucleotide sequence covering entire genome of HBV (3,215 bases) derived from the liver of donor 3 had a homology of 99.8-100% with that derived from the serum of corresponding recipient 3. The strain of recipient 3 showed the closest association with that of the donor 3 by phylogenetic analysis. Complete sequences from two recipients with de novo HBV infection including recipient 3 conserved the basic organisation of HBV genome. Analysis of the entire nucleotide sequence of HBV genome proved that HBV existed in the liver of the donor with anti-HBc, and it caused de novo infection in the corresponding recipient.     

献血人群隐匿性乙型肝炎病毒感染的流行病学和血清学研究

目的了解广州地区献血人群隐匿性乙型肝炎病毒感染（OBI）的流行病学和血清学情况。方法对广州地区199631例无偿献血者标本同时用ELISA法检测HBsAg、紫外-乳酸脱氢酶法检测ALT、核酸扩增技术（NAT）联合检测HBV/HCV/HIV及HBV单项鉴别试验,对HBsAg阴性HBV DNA阳性者进行随访,用荧光定量PCR检测病毒载量,用ELISA法检测乙肝两对半。结果 199631例标本中共检出104例HBsAg阴性HBV DNA阳性者,经随访有54例为OBI,OBI检出率为0.027%,年龄以46～55岁组检出率最高（P〈0.01）,外地身份证的献血者检出率高于广州市身份证者（P〈0.01）,OBI检出率与性别和献血次数无关（P〉0.05）。104例HBsAg阴性HBV DNA阳性的标本ALT均正常,病毒载量均〈1000IU/ml,平均值为162IU/ml。随访标本中,除6例ALT异常外其余均正常,54例OBI标本病毒载量均〈1000IU/ml,平均值为122IU/ml,乙肝两对半中抗-HBc阳性率明显高于其他项目（P〈0.01）。结论 HBsAg阴性献血者中存在OBI,有必要在献血者中开展核酸检测。     

A Novel Strategy for the Prevention of Hepatitis B Virus-Related Hepatitis Following Allogeneic Hematopoietic Stem Cell Transplantation from Hepatitis B Surface Antigen-Positive Donors

Hematopoietic stem cell transplantation (HSCT) is increasingly being applied globally. Cases in which healthy HSCT donors are chronically infected with hepatitis B virus (HBV) are relatively common in areas where HBV is endemic. Recipients of stem cells from such hepatitis B surface antigen (HBsAg)-positive donors are at risk of viral infection, and thus may develop HBV-related hepatitis. Given the lack of standardized approach to minimizing the risk of such infections from HBsAg⁺ donors during HSCT, we conducted this study with the aim of developing an efficient strategy to address this challenge. A strategy comprising antiviral treatment for detectable HBV-DNA in HBsAg⁺ donors, hepatitis B immune globulin (HBIG) administration in HBsAg^– recipients with passive immunity, and prophylactic antiviral treatment for HBsAg⁺ recipients was developed. The strategy was validated using a case-control study of 40 recipients who received stem cells from HBsAg⁺ donors (group A) and 40 pair-matched controls who received stem cells from HBsAg^– donors (group B). The cumulative incidence of HBV-related hepatitis was relatively similar in the 2 groups (group A: 8.5%; 95% confidence interval [CI], -.9% to 17.9%; group B: 7.9%; 95% CI, -.9% to 16.7%; P = .939). In HBsAg^– recipients who received passive immunity from HBIG treatment, a significant negative linear correlation was observed between HBsAb titer in vivo and time in the first year after allo-HSCT (R² = .23; P < .001). This method was cost-effective, with a median cost of all HBV management of USD 332.1 (range, 172.7 to 1985.3), compared with USD 1464.9 (range 409.9 to 1985.3) for conventional strategies (P < .001). The novel strategy presented in here is robust in preventing HBV-related hepatitis after allo-HSCT with stem cells from HBsAg⁺ donors. This is important for the effective application of allo-HSCT in HBV-endemic areas without precluding the use of HBsAg⁺ donors.     

乙型肝炎免疫球蛋白阻断乙型肝炎病毒母婴传播的临床研究

目的探讨乙型肝炎（乙肝）表面抗原（HBsAg）阳性孕妇及其新生儿采用乙肝免疫球蛋白（HBIG）阻断乙型肝炎病毒（HBV）母婴垂直传播的效果。方法将136例HBsAg（＋）的孕妇分为观察组（72例）和对照组（64例）,观察组孕妇于孕28、32与36周分别注射乙型肝炎免疫球蛋白（HBIG）,双阳性注射400IU,单阳性注射200IU;对照组只作随访及常规产检。两组的新生儿在出生6h内、第1、6个月时分别注射乙肝疫苗（HBvac）10μg、5μg、5μg;观察组新生儿在出生6h内臀部肌内注射HBIG 100IU。分别检测两组新生儿及6月龄婴儿血清中HBsAg、乙型肝炎表面抗体（HBsAb）及HBV DNA。结果观察组新生儿HBsAg和HBV DNA阳性率较对照组低,差异有统计学意义（P〈0．05和P〈0．01）。观察组6月龄婴儿HBsAb阳性率较对照组高,而HBV DNA阳性率较对照组低,差异也均有统计学意义（P〈0．01和P〈O．05）。结论HBsAg（＋）的孕妇应用HBIG可有效阻断HBV母婴传播,而新生儿出生时应用HBIG和HBvac联合免疫,可明显提高6月龄婴儿HBsAb阳性率。     

衢州市无偿献血者中隐匿性HBV感染的基因型别及突变类型分析

目的 了解衢州市无偿献血者隐匿性乙肝病毒感染情况及病毒的分子生物学特征.方法 对衢州市中心血站24 178例无偿献血者血液用北京万泰和Sorin公司生产的ELlSA试剂盒进行HBV的初检和复检,对HBsAg阴性标本进行HBV DNA检测,从而检出隐匿性乙肝病毒感染者,再对HBV DNA 阳性标本进行 S 基因片段序列分析和氨基酸突变分析,从而了解本市无偿献血者隐匿性乙肝病毒感染情况和病毒分子生物学特征,探讨隐匿性乙肝病毒感染的可能机制.结果 24 178例无偿献血者标本中,158例HBsAg阳性,24 020例HBsAg阴性标本中,15例HBV DNA阳性,隐匿性HBV感染比例为0.62‰（15/24 020）,其中基因C型9例（60％）,基因B型6例（40％）;S基因“a”表位氨基酸突变分析显示有11例隐匿性HBV感染病毒株在“a”表位发生突变.结论 衢州市无偿献血者中存在一定比例隐匿性乙肝病毒感染,隐匿性乙肝病毒感染与病毒基因突变有相关性.     

Association of polymorphisms in interleukin-18 and interleukin-28B with hepatitis B recurrence after liver transplantation in Chinese Han population

Interleukin-18 (IL-18) is a potent proinflammatory cytokine, which can promote hepatitis B virus clearance. The latest studies find that genetic polymorphisms near the IL-28B gene are strongly associated with sustained viral response and spontaneous viral clearance in patients with chronically infected hepatitis C and hepatitis B. We investigated the effect of rs187238 and rs1946518 in IL-18 gene and rs8099917 in IL-28B gene on HBV recurrence in liver transplant patients. A total of 200 liver transplant recipients and relevant donors were enrolled in this study. The patients' mean follow-up was 39 month (range 10-65 month). All liver transplant recipients were in a stable stage. The total recipients (n = 200) were divided into end-stage liver disease secondary to hepatitis B (n = 140) and end-stage liver disease secondary to other diseases (n = 60) before transplantation. Recipients (n = 140) with hepatitis B before transplantation were defined to nonHBV recurrence group (n = 119) or HBV recurrence group (n = 21), which was positive for HBsAg or elevatory in HBV DNA (>2.0 × 10(2) IU mL(-1)) after transplantation. For the recipients (n = 140) had hepatitis B before transplantation, we studied the single-nucleotide polymorphisms (SNPs) of IL-18 gene (rs187238 and rs1946518) and IL-28B gene (rs8099917) by high-resolution melting (HRM) curve analysis. The serum levels of IL-18 and IFN-γ were tested by ELISA. The serums levels of IFN-γ were lower in HBV recurrence group than that in nonHBV recurrence group (P < 0.01). The genotype of IL-28B gene rs8099917 was associated with alanine aminotransferase (ALT) levels and aspartate aminotransferase (AST) levels in HBV-related liver transplant recipients (n = 140). The recipients with allele G (GG+GT) had higher ALT and AST levels (P < 0.05). No association was found between IL-18 gene and IL-28B gene polymorphisms with HBV recurrence in the liver transplant recipients or the donors. We identified that the IFN-γ was a protective factor of HBV recurrence after liver transplantation. The allele G of rs8099917 was associated with hepatitis B-related hepatocytes injury. The rs8099917 G allele subgroup should reinforce antiviral therapy.     

Hepatitis B Virus Antigens in Peripheral Blood Mononuclear Cells during the Course of Viral Infection

We studied the expression of surface (HBsAg) and core (HBcAg) proteins of hepatitis B virus (HBV) on the surface of peripheral blood mononuclear cells (PBMC) from HBV-infected patients. A total of 122 patients with different liver viral diseases was analyzed by indirect immunofluorescence with monoclonal antibodies. The 35 patients with HBV chronic active hepatitis (CAH) and 38 of 60 patients with acute hepatitis B (63%) expressed HBsAg on the PBMC. No expression was detected on the cells from both normal and HBV-unrelated viral hepatitis control groups. Serial follow-up of patients with acute hepatitis B showed that HBsAg expression by PBMC tended to be undetectable 4 months after the onset of the disease and at the same time the clinical improvement was evident. Cell cultures of EBV-transformed B lymphocytes were established from PBMC of HBV-infected patients; immunoelectron microscopy demonstrated the HBsAg on the cellular membrane. One-third of HBV-infected patients who were studied showed the expression of HBcAg by PBMC. HBcAg was detected in patients with acute hepatitis B at the early stage of infection. The cells of these patients also expressed HBsAg in PBMC. In CAH patients, a positive association was observed between the expression of HBcAg and the presence of serum HBeAg.