妊娠中晚期注射HBIG对阻断乙肝病毒母婴传播的分析

目的:目前临床普遍建议乙肝孕妇妊娠中晚期注射乙肝免疫球蛋白( HBIG)以阻断母婴传播,为验证其效果,做以下研究.方法:乙肝血清指标HBsAg和HBeAg双阳性孕妇妊娠中晚期注射HBIG共三次(实验组)与未注射孕妇(对照组)所产幼儿于5岁采血检测HBsAg及抗-HBs,将两组进行比较. 结果:孕晚期预防性应用HBIG组孕妇所产新生儿随访5年后,两组幼儿的HBsAg反抗-HBs阳性率无统计学差异(P＞0.05).结论:新生儿应用乙肝免疫球蛋白与乙肝疫苗联合免疫能有效阻断HBV母婴传播,妊娠中晚期注射HBIG并不能更加有效的提高乙肝病毒母婴传播的阻断率.所以己肝孕妇妊娠中晚期注射乙肝免疫球蛋白(HBIG)的治疗效果有待研究.     

孕晚期注射乙肝免疫球蛋白对乙型肝炎病毒母婴传播阻断率影响的探讨

目的 探讨孕晚期注射乙肝免疫球蛋白(HBIG)对乙型肝炎病毒(HBV)母婴传播阻断率的影响.方法 对103例慢性HBV携带孕妇于孕晚期按1:1比例随机分为注射HBIG组和对照组,两组新生儿出生2 h内均尽快注射HBIG 200 IU,基因重组酵母乙肝疫苗每次10μg,按0、1、6月方案注射.新生儿于7月龄及12月龄时检测外周血HBV标记物.结果 孕晚期注射HBIG组51例和对照组52例孕妇所生新生儿共103例,在7月龄、12月龄时均无HBV携带,阻断率均达100%.结论 新生儿出生2 h内尽快注射HBIG 200 IU,同时按0、1、6月方案规范注射乙肝疫苗,即可获得满意的HBV母婴传播阻断效果;孕晚期注射HBIG对提高HBV母婴传播阻断率无显著意义.     

慢性乙型肝炎母婴传播的影响因素新进展

乙型肝炎病毒(HBV)传播的主要途径是母婴传播,对母亲HBs Ag阳性的新生儿进行联合免疫(HBIG+乙肝疫苗),母婴阻断成功率可达90%~95%,但对于高病毒载量的母亲,在联合免疫的情况下,仍有8%~32%的婴儿在围生期感染HBV,在围产期感染HBV者有90%发展成慢性感染,这些慢性感染者有15%~25%死于肝硬化和肝癌。因此,对HBV感染的孕妇进行管理及制定阻断HBV母婴传播的策略对降低母婴传播率至关重要。由于人们对此类问题的敏感性,临床试验难以进行。本文将从HBV母婴传播模式和影响因素等方面进行综述。     

原位杂交检测乙肝携带者精子和卵巢颗粒细胞中HBV-DNA

乙型肝炎是世界性的传染病,我国乙肝病毒(HBV)携带者高达1.3亿[1].为阻断HBV的传播,我们采取对新生儿联合应用乙肝疫苗及乙肝免疫球蛋白但仍有10%～20%得不到保护[2].为探讨是否存在通过生殖细胞传播的 HBV,本研究采用原位杂交技术检测男性携带者精子及女性携带者卵巢颗粒细胞中HBV-DNA,旨在为HBV的防治提供依据.     

乙型肝炎病毒表面抗原和e抗原双阳性乙型肝炎病毒高载量孕妇孕晚期应用替比夫定行母婴阻断的疗效

目的评价妊娠晚期对乙型肝炎病毒（HBV）表面抗原（HBsAg）和HBV e抗原（HBeAg）双阳性的高HBV载量孕妇应用替比夫定行HBV感染母婴阻断的疗效。 方法选取2007年7月1日至2017年6月30日于首都医科大学附属北京地坛医院产科门诊进行系统产前检查的慢性HBV感染孕晚期（妊娠28周）孕妇及其分娩婴儿作为研究对象，分析血清HBsAg和HBeAg双阳性、肝功能正常、HBV DNA≥ 1 × 10⁶拷贝/ml，且获得完整随访资料的孕妇共250例，向患者充分告知HBV母婴阻断孕期抗病毒用药的利弊，根据知情自愿原则，按照患者是否服用替比夫定，分成替比夫定组（150例）及对照组（100例）。替比夫定组孕妇自孕28周起口服替比夫定600 mg/d，至分娩后42 d止。对照组孕妇则不应用抗病毒药物。检测两组受试者在孕28周和分娩时血清HBV DNA载量；观察替比夫定组孕妇服药后出现的不良反应。两组孕妇的婴儿出生后均接受主、被动联合免疫；在出生6 h内、1月龄和6月龄时肌内注射乙肝疫苗各10 μg，均于出生后6 h内和1月龄时肌肉注射乙肝免疫球蛋白各200 IU。检测婴儿出生后6 h内（于主、被动免疫前抽股静脉血）和7月龄血清HBsAg阳性率及HBV DNA载量。 结果服药后分娩前替比夫定组孕妇平均HBV DNA载量显著低于对照组，差异有统计学意义（t = 31.07、P < 0.001）。替比夫定组与对照组婴儿出生6 h内血清HBV DNA阳性率（0.00% vs. 17.00%）差异有统计学意义（χ² = 27.36、P < 0.001）；新生儿7月龄时，替比夫定组HBV DNA载量均低于检测下限，对照组婴儿HBV DNA阳性率为10.00%。经Fisher精确检验，对照组婴儿宫内感染率显著高于替比夫定组（12.00% vs. 0.00%），差异有统计学意义（P < 0.001）。替比夫定组使用随访期间未发现严重不良反应，且该组婴儿未发生出生缺陷。 结论随着分娩前孕妇血清HBV DNA载量升高，HBV宫内感染的危险性增加。肝功能正常、HBsAg及HBeAg双阳性，HBV DNA高载量孕妇孕晚期应用替比夫定抗病毒治疗可显著降低妊娠晚期孕妇血清HBV DNA载量，有效阻断HBV宫内感染，对母婴均具有良好的安全性。     

乙型肝炎病毒的夫妻间传播及其预防的研究

乙型肝炎严重危害人类健康,研究发现,夫妻间传播也是乙型肝炎病毒(HBV)传播的重要途径之一.但由于目前缺乏大规模流行病学资料,HBV在夫妻间的传播长期被忽视.选择1999年1月至2006年12月我院门诊新婚体检中发现的HBV感染者的血清乙型肝炎病毒标志物(HBV-M)全阴的配偶注射乙肝疫苗和乙肝免疫球蛋白(HBIG)预防HBV传播,取得十分满意的预防效果,现报告如下.……     

乙型肝炎病毒产前垂直传播机制及其阻断研究

众所周知,垂直传播是感染乙型肝炎病毒（HBV）的重要途径之一,广义的垂直传播途径包括经生殖细胞、宫内感染、分娩及产后接触等,在时间上则可分为产前、产时和产后3个阶段。对产时、产后两种传播方式,现在通过联合使用乙型肝炎免疫球蛋白（HBIG）和乙型肝炎疫苗对新生儿进行主-被动联合免疫,已经使HBV感染率有了明显的下降,阻断率可达90％,但仍有10％左右的新生儿未能避免HBV感染,即免疫失败。     

乙型肝炎及丙型肝炎病毒污染针具刺伤6例的紧急处理

目的我院近年来6例工作人员被乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）污染针具刺伤后紧急处理方法及效果。方法被预防针刺伤的医护人员在反复挤压伤口、反复局部消毒后尽可能早的注射乙肝免疫球蛋白，1周后注射乙肝疫苗。被丙肝病人针具刺伤后注射胸腺肽注射液。结果立即注射高效价乙肝免疫球蛋白及胸腺肽，其能随时中和进入血液的HBV、HCV病毒，是迅速有效的人工被动免疫；HBV进入肝细胞大量复制前即刺激人体产生抗－HBs形成主动免疫，清除HBV。结论此种处理方法是有效、可靠的，说明乙肝免疫球蛋白、胸腺肽与乙肝疫苗及时实施序贯注射是有效保护该类伤者的主要措施。     

乙型肝炎病毒母婴传播婴儿11例感染因素分析

目的分析11例婴儿发生HBV母婴传播的原因和时间,为采取措施进一步降低HBV母婴传播提供临床依据。 方法对2010年12月至2012年6月首都医科大学附属北京地坛医院收治的409慢性HBV感染母亲分娩的409例婴儿随访观察,所有婴儿均在出生后2 h内、15~30 d各注射乙肝免疫球蛋白（HBIG）200 IU,并按0-1-6方案接种重组酵母乙肝疫苗10 μg。采用微粒子化学发光法（CMIA）、荧光定量聚合酶链反应技术检测婴儿出生时外周静脉血的血清学标志物（HBsAg、抗-HBs、HBeAg、HBeAb、HBcAb）和HBV DNA,并于婴儿1个月、7个月~3岁随访。409例慢性HBV感染母亲按照血清HBV DNA水平高低分为3组,分别为HBV DNA阴性组147例患者（< 5 × 10²拷贝/ml）、低病毒含量组124例患者（≥ 5 × 10²~< 1.00 × 10⁶拷贝/ml）、高病毒含量组138例患者（≥ 1.00 × 10⁶拷贝/ml）。多因素Logistic回归分析喂养方式、分娩方式、母亲血清HBV DNA和HBVeAg水平对母婴传播的影响。 结果发生母婴传播的11例婴儿中,45.45%（5/11）婴儿从出生至1月龄HBsAg、HBV DNA持续阳性,1月龄时HBsAg均> 250 IU/ml、HBV DNA均> 1.00 × 10⁶拷贝/ml,免疫失败,全部进展为慢性感染,分析为宫内感染;54.55%（6/11）婴儿出生时至1个月龄无明确感染,抗-HBs均阳转,但在7月龄时5例婴儿、12月龄时1例婴儿发生HBsAg、HBV DNA阳转,分析为产后感染。HBV DNA阴性组、低病毒载量组和高病毒载量组婴儿感染率分别为0、0.81%（1/124）和7.25%（10/138）,高病毒载量组较低病毒载量组婴儿感染风险高8.98倍（P = 0.01）。多因素Logistic回归分析显示母亲血清HBV DNA水平是影响母婴传播的的独立危险因素（95%CI：1.28~6.39、P = 0.01）。 结论婴儿出生后经严格主-被动联合免疫,血清高病毒载量母亲分娩婴儿仍有HBV母婴传播风险,母婴传播的原因除宫内感染外,产后感染亦是母婴传播的重要因素,特别在被动免疫消失,主动免疫尚未产生时,婴儿存在较大母婴传播风险。     

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。     

替比夫定阻断孕晚期HBV母婴传播的疗效及安全性Meta分析

目的：评价替比夫定阻断HBV母婴传播的效果和安全性。方法检索2010年1月至2012年12月万方数据、中国知网和NCBI数据库,根据纳入标准、排除标准,对入选随机对照试验（RCT）的研究结果,采用RevMan 5.0软件进行分析。结果共检索到符合标准的文献8篇,共518例。替比夫定组治疗后孕妇HBV DNA水平显著下降,差异具有统计学意义（OR =3.95,95%CI：3.61～4.28, P ＜0.00001）。替比夫定组婴儿在出生时HBsAg阳性率和HBV DNA阳性率均显著低于对照组,差异有统计学意义（OR =0.28,95%CI：0.17～0.46,P ＜0.00001;OR =0.22,95%CI：0.12～0.40,P＜0.00001）;随访6个月时婴儿HBsAg阳性率和HBV DNA阳性率均低于对照组,差异具有统计学意义（OR =0.17,95%CI：0.80～0.35,P ＜0.00001;OR =0.12,95%CI：0.05～0.29,P ＜0.001）;替比夫定组和对照组孕妇在服药期间和婴儿的的不良反应发生率无明显差异。结论替比夫定能够安全、有效地阻断母婴传播。     

Prophylactic use of low-dose, on-demand, intramuscular hepatitis B immunoglobulin and lamivudine after liver transplantation

The combination of hepatitis B immunoglobulin (HBIG) and antivirals (nucleos[t]ide analogs) has extended the applicability of orthotopic liver transplantation (OLT) for patients with hepatitis B virus (HBV)-related liver disease. However, HBIG administrations have an extremely high cost. Herein, we evaluated our results with low-dose, on-demand, intramuscular HBIG plus lamivudine (LAM) prophylaxis after OLT. The HBV DNA status in 40 patients at the time of OLT determined the treatment: group A (n = 22), HBV DNA (-), no antiviral pretreatment; group B (n = 11), HBV DNA (-), after LAM; group C (n = 3), HBV DNA (+) after LAM (LAM resistance/Adefovir [ADV] unavailable); group D (n = 2), HBV DNA (+), no antiviral pretreatment; and group E (n = 2), HBV DNA (-) after LAM + ADV (LAM resistance/ADV available). Five patients died within 12 months after OLT unrelated to HBV infection. The remaining 35 patients were followed for a median duration of 16 months (range, 6-93 months). Only two recipients from group C, who were transplanted despite LAM resistance + no ADV pretreatment, revealed recurrent HBV infections at 14 and 16 months posttransplantation; they were then treated successfully with ADV as it became available. The third group C recipient had undetectable HBV DNA at 18 months after OLT. The mean cumulative doses of HBIG administered within the first, second, and third years were 34,014, 5258, and 5090 IU, respectively. In conclusion, low-dose, on-demand, intramuscular HBIG plus (LAM +/- ADV) prophylaxis is a safe, efficient, and cost-effective regimen to prevent recurrent HBV infection following OLT. OLT despite untreated LAM resistance may require sustained higher serum HBsAb levels after surgery.     

Prevention of hepatitis B virus recurrence after liver transplantation

Abstract:  Liver transplantation for hepatitis B virus (HBV)-related liver disease has changed from a contraindication to outcomes comparable with non-HBV-related liver transplantations during the last two decades. Mainly the implementation of immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and the use of nucleoside analogs such as lamivudine and adefovir account for this dramatic change. The standard of care in most centers today consists of lamivudine treatment in replicating hepatitis B pre-orthotopic liver transplantation (OLT) and a combination regimen of lamivudine and HBIG post-OLT. With adefovir, a potent antiviral drug became available in recent years that allows for the treatment of patients with lamivudine-resistant tyrosine-methionine-aspartate-aspartate (YMDD)-mutant HBV. In the transplantation setting, first studies indicate that a triple prophylactic therapy consisting of lamivudine, adefovir, and HBIG will become the standard of care for YMDD-mutant-related hepatitis B. With new drugs emerging for the treatment of chronic HBV, there is optimism for new options also in the transplant setting.     

Efficacy and Safety of Hepatitis B Virus Vaccination Following Hepatitis B Immunoglobulin Withdrawal After Liver Transplantation

BackgroundHepatitis B immunoglobulin (HBIG) and oral nucleoside/nucleotide analogs have been the mainstay of hepatitis B virus (HBV) prophylaxis after liver transplantation. However, long-term HBIG administration could have disadvantages, such as an increase in medical costs and the development of mutant HBV strains. This study aimed to investigate the safety and efficacy of HBV vaccination after the withdrawal of HBIG after liver transplantation.MethodsThis prospective open-label single-arm observational clinical trial enrolled 41 patients who underwent liver transplantation between 2010 and 2016 because of a condition related to chronic HBV infection. At the time of enrollment, all patients had taken entecavir and discontinued HBIG administration. When hepatitis B surface antibody titer was undetectable after the withdrawal of HBIG, a recombinant HBV vaccine was injected intramuscularly at month 0, 1, and 6.ResultsAfter excluding 5 patients who dropped out and 2 patients who had a persistent hepatitis B surface antibody titer, 9 (26.5%) of 34 patients had a positive vaccination response. The median hepatitis B surface antibody titer at seroconversion was 86 (12-1000) IU/L, and those at the end of follow-up were 216 (30-1000) IU/L. No patients experienced HBV recurrence during the study period. Sex (female, odds ratio 32.91 [1.83-592.54], P = .018) and the dosing interval of HBIG before withdrawal (≥90 days, 16.21 [1.21-217.31], P = .035) were independent contributing factors for positive response to the vaccination.ConclusionHBV vaccination still deserves consideration as active immunoprophylaxis after liver transplantation because it could provide added immunity to nucleoside/nucleotide analogs monotherapy with excellent cost-effectiveness.     

Lamivudine or lamivudine combined with hepatitis B immunoglobulin in prophylaxis of hepatitis B recurrence after liver transplantation: a meta-analysis

There is a controversy over whether the different outcomes of prophylaxis of hepatitis B virus (HBV) recurrence are attributable to different treatments. A systematic review and a meta-analysis were conducted to evaluate lamivudine monotherapy and combined therapy of lamivudine and hepatitis B immunoglobulin (HBIG) in HBV infected liver recipients. A fixed effects model was used for statistical pooling of relative risks (RR) for the different outcomes. Six articles (551 patients) fulfilled the inclusion criteria. Statistically significant differences were observed between lamivudine monotherapy and lamivudine + HBIG therapy in hepatitis B recurrence [ P  < 0.0001; RR = 0.38; 95% CI (0.25, 0.58)], YMDD mutant [ P  = 0.002; RR = 0.40; 95% CI (0.23, 0.72)] and hepatitis B recurrence in HBV-DNA positive patients before orthotopic liver transplantation [ P  < 0.00001; RR = 0.31; 95% CI (0.21, 0.45)]. No significant differences were observed in patient survival [ P  = 0.59; RR = 1.02; 95% CI (0.95, 1.09)], graft survival [ P  = 0.56; RR = 1.02; 95% CI (0.95, 1.09)] and diseases leading to death between the two groups [HBV recurrence leading to death: P  = 0.05; RR = 0.47; 95% CI (0.22, 1.02); hepatocellular carcinoma recurrence leading to death: P  = 0.13; RR = 0.34; 95% CI (0.09, 1.36)]. In conclusion, combination of lamivudine and HBIG can effectively decrease the recurrence rate of HBV and the incidence of YMDD mutant, but it can not improve patient survival and graft survival significantly. Well-designed large-sample trials are needed to evaluate the efficiency of combined therapy of lamivudine and HBIG in prophylaxis of HBV recurrence in liver graft recipients.     

乙型肝炎病毒感染孕妇替比夫定母婴阻断及其对婴儿乙肝疫苗免疫应答的影响

目的探讨高病毒载量乙型肝炎病毒(HBV)感染的孕妇应用替比夫定行母婴阻断疗效,及其对乙肝疫苗免疫应答的影响。方法回顾性收集2017年10月1日至2019年12月30日于首都医科大学附属北京地坛医院产检并分娩的慢性HBV感染202例孕妇及其分娩婴儿,选取孕中期HBV DNA>2.0×105 IU/ml的孕妇,其中132例孕中晚期给予替比夫定行抗病毒治疗者为研究组,未服用抗病毒药物的70例孕妇中剔除3例母婴阻断失败者为对照组(67例)。两组孕妇所产新生儿出生后2 h内均给予乙肝疫苗10μg及100 IU乙肝免疫球蛋白,出生后1个月、6个月常规给予10μg乙肝疫苗免疫接种。采用微粒化学发光法检测1岁婴儿乙型肝炎病毒表面抗体(HBsAb)水平,采用非参数秩和检验比较两组婴儿对乙肝疫苗的免疫应答。两组孕妇及其新生儿呈正态分布的计量资料采用独立样本t检验,非正态分布的计量资料采用非参数检验;计数资料采用Pearson卡方检验或连续校正卡方检验进行分析。结果入组202例孕妇中,服用替比夫定者与未服用者母婴阻断失败率[0(0/130)vs.4.29%(3/70)]差异有统计学意义(χ^(2)=5.74、P=0.017)。研究组和对照组孕妇年龄(t=-1.62、P=0.110)、孕次(t=0.27、P=0.787)、产次(t=1.325、P=0.187)、体重(t=0.55、P=0.580)、孕中期丙氨酸氨基转移酶(ALT)(Z=-0.19、P=0.85)及HBV DNA载量(t=0.49、P=0.620)、剖宫产率(χ^(2)=0.71、P=0.400)及孕产期并发症等差异均无统计学意义。研究组和对照组孕妇分娩前HBV DNA载量[(3.74±0.78)lgIU/ml vs.(7.29±0.71)lgIU/ml]差异有显著统计学意义(t=31.88、P<0.001)。两组孕妇所产新生儿出生孕周(t=1.72、P=0.090)、身长(t=0.39、P=0.696)、出生体重(t=-0.13、P=0.90)、性别(χ^(2)=0.25、P=0.620)、Apgar评分(t=0.213、P=0.832)、1岁时体重(t=-0.20、P=0.840)、ALT(Z=-0.40、P=0.690)及HBsAb水平(Z=0.76、P=0.450)差异均无统计学意义。研究组孕妇所产婴儿1岁时对乙肝疫苗免疫无应答率、弱应答率和强应答率分别3.79%(5/132)、22.73%(30/132)和73.48%(97/132);对照组分别为0(0/67)、14.93%(10/67)和85.07%(57/67),差异无统计学意义(Z=-1.93、P=0.054)。结论替比夫定可显著降低HBV感染孕妇的HBV DNA载量,提高母婴阻断成功率;孕期应用替比夫定抗病毒治疗不影响婴儿对乙肝疫苗的免疫应答。     

Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis

BACKGROUND: The present scarcity of organ donors requires consideration of grafts from sources not previously used. Several studies have addressed the use of grafts from donors who have antibodies to the hepatitis B core antigen (anti-HBc+). The aim of this study was to evaluate the impact of the use of anti-HBc+ grafts in patients transplanted for hepatitis B virus (HBV)-related cirrhosis. METHODS: Recipients of first hepatic transplants from donors with antibodies to HBV were identified retrospectively. All patients who had serology suggestive of active HBV and were negative for hepatitis C and D were included in the analysis. The Kaplan-Meier method was used to assess the actuarial recurrence-free survival on patients with graft survival longer than 1.5 months. The stepwise Cox regression model was used to identify independent predictors of HBV recurrence. RESULTS: One thousand seven hundred seventeen first liver transplants were performed at the Thomas E. Starzl Transplantation Institute from September 1, 1990, to December 31, 1999. HBV was the cause of cirrhosis in 112 patients (6.5%). Thirty-three patients had coexistent viral infection (23 HCV and 10 HDV). Fourteen donors (17.2%) were positive for HBV markers, with nine anti-HBc+ and with five both anti-HBc+ and anti-HB surface-positive; of these, 13 anti-HBc+ organ recipients had long-term survival. Nine (69.2%) of these cases were reinfected versus 20 (35.7%) in the group that received grafts from HBV- donors (P<0.05, Fisher's exact test). The mean time to reinfection was shorter in the anti-HBc+ group (2.9 yr vs. 6.4 yr, P<0.005). There were no statistical differences in graft or patient survival between the two groups. HBV prophylaxis with combined lamivudine and hepatitis B immunoglobulin (HBIG) significantly reduced the reinfection rate (P<0.03). Hepatitis Be (Hbe) antigen-positive recipients trended to faster reinfection (not significant). Cox regression analysis revealed that both anti-HBc graft donor status (RR, 2.796; P=0.020) and combination of lamivudine/HBIG (RR, 0.249; P=0.021) are independently associated with reinfection. CONCLUSIONS: The use of anti-HBc+ liver grafts does not affect graft or patient survival. However, patients who receive these organs are 2.5 times more likely to develop HBV recurrence. Lamivudine and HBIG combination decreases HBV recurrence 4-fold.     

Prevention of hepatitis B virus reinfection after orthotopic liver transplantation

OBJECTIVE: We discuss the prevention of hepatitis B virus reinfection following orthotopic liver transplantation. METHODS: Sixty-eight cases of chronic fulminant hepatitis B, the end stage of liver cirrhosis and liver carcinoma complicated with HBV cirrhosis, were given antiviral drugs pre- and posttransplantation to prevent hepatitis B virus reinfection. Lamivudine was administered to two cases and lamivudine + HBIG to 63 cases. Adefovir + HBIG was administered to three cases. The serum HBV, HBV DNA, liver biopsy immunohistochemistry and clinical examinations were performed. RESULTS: One of two cases given lamivudine developed reinfection with serum HBSAg, HbeAb, HBcAb, HBV DNA, and positive and liver biopsy immunohistochemistry showing HBSAg phenotype. Two of the 63 cases given lamivudine + HBIG developed reinfection with serum HBSAg, HBeAb, HBcAb positive and liver biopsy immunohistochemistry showing HBSAg phenotype. The serum HBV DNA was positive in one of the two cases. Three cases given adefovir developed no reinfection with HBV. CONCLUSION: Orthotopic liver transplantation is an effective treatment for HBV infection; lamivudine + HBIG or adefovir + HBIG prevent hepatitis B virus reinfection.