第003例——纳差、乏力、尿黄

病历摘要 患者男,51岁,异体肝移植术后2年8个月,因进行性黄疸到本院就诊.患者因乙型肝炎肝硬化(失代偿期)并原发性肝癌,于2004年11月行异体原位肝移植(orthotopic liver transplantation,OLT).术前查HBsAg阳性、HBcAb阳性,术后服用拉米夫定100 mg/d抗病毒治疗,并间断肌注高效价乙肝免疫球蛋白(HBIG),保持HBsAb滴度大于100 IU/L、HBsAg阴性.     

肝移植术后乙肝主动免疫重建受者停用HBIG和（或）核苷（酸）类似物的长期安全性和有效性

目的 探讨乙型病毒性肝炎（乙肝）相关疾病肝移植受者接种乙肝疫苗成功后长期停用乙型肝炎免疫球蛋白（HBIG）和（或）核苷（酸）类似物（NAs）预防乙型肝炎病毒（HBV）再感染的安全性及有效性。方法 回顾性分析76例接种乙肝疫苗后成功重建乙肝主动免疫的肝移植受者的基本资料,分析疫苗接种及应答情况、应答者停用HBIG和（或）NAs的随访结果、停用HBIG和（或）NAs后HBV再感染情况。结果肝移植术后至开始接种乙肝疫苗的时间间隔为26(20,40)个月。接种疫苗至应答时间为15(8,27)个月。初始76例受者全部停用HBIG,36例受者停用HBIG和NAs。随访期间,76例停用HBIG受者中12例恢复使用HBIG,36例停用HBIG和NAs者中16例恢复使用NAs。HBIG和NAs停用时间分别为135(98,150)个月与133(34,149)个月。16例应答者未接种过加强针,36例应答者定期接种加强针,第1次接种加强针的时间距离停用HBIG的间隔时间为44(11,87)个月,未接种加强针和接种加强针的应答者一般资料比较差异均无统计学意义（均为P>0.05）。截至随访日,9例受者失访,...     

胸腺肽a1改善血液透析患者乙型肝炎疫苗免疫应答的临床研究

目的:维持性血液透析(Hemodi al ysi s,MHD)患者为乙型肝炎病毒(Hepat i t i sB Vi rus,HBV)感染的高危人群,改善其对乙型肝炎疫苗的免疫应答有重要的临床意义,而通过临床发现,相当多的MHD患者对常规乙型肝炎疫苗的应答差,血清转换率低下。本研究探讨了对MHD患者应用胸腺肽a1改善其对乙型肝炎疫苗免疫应答的效果。方法:采用多中心、随机的方法,将79例具备正常转氨酶水平、HBsAg(-)、Ant i-HBc(-)及Ant i-HBs(-)的MHD患者随机分为两组,A组MHD患者39例,进行常规疗程(O月、1月、6月)肌内注射普通基因重组乙肝疫苗,10μg/针,每次注射剂量为2针20μg,共三次6针,总剂量为60μg;B组MHD患者40例,按A组方法行乙肝疫苗接种,随后行胸腺肽a1皮下注射,每次1.6mg,每周2次,连续用4周(共8针),第一针在疫苗注射后立即皮下注射。以乙肝表面抗体滴度≥10 ml U/ml为产生保护性血清转换。注射结束后3个月检测乙肝表面抗体滴度,分析两组之间保护性血清转换率及抗体滴度水平的差异。结果:A组患者有26例产生了保护性抗体,保护性血清转换率为66.67%,B组患者有37例产生了保护性抗体,保护性血清转换率为92.50%,两组差异有统计学意义(P<0.01);同时B组的抗体滴度明显高于A组,两组差异有统计学意义(P<0.01)。两组患者抗体滴度水平与患者性别、年龄、病程、肌酐水平、白蛋白水平、血红蛋白水平等无明显相关性(P>0.05)。结论:MHD患者对常规基因重组乙肝疫苗的免疫应答低下,胸腺肽a1可明显改善MHD患者的免疫应答,增强乙肝疫苗的免疫效果,故可减少MHD患者感染乙肝的概率,改善其生存质量。     

磁微粒化学发光法定量检测525名儿童表面抗体结果分析

目的:简要了解我市儿童乙型肝炎(下称乙肝)病毒表面抗体的浓度,以观察该群体抵御乙肝痛毒侵入的能力.方法:以磁徽粒化学发光免疫分析仪定量检测525名儿童的乙肝病毒表面抗体(HBsAb)浓度,然后对所有结果进行统计分析.结果:在525名儿童中,乙肝病毒表面抗体(HBsAb)浓度值≤10mIU/ml 126人,完全不具有抵御乙肝病毒(HBV)入侵的能力,需要立即进行乙肝疫苗的接种;HBsAb浓度值在10-100mIU/m1 150人,具有部分抵御HBV入侵的能力,需要进行乙肝疫苗加强接种;HBsAb浓度值≥100mIU/ml 249人,具有抵御HBV入侵的能力,不需要进行乙肝疫苗接种.结论:许多儿童不具有和不完全具有抵御HBV入侵的能力,需要进行乙肝疫苗接种,以预防乙肝.     

肝移植术后乙型肝炎复发的预防和治疗

目的探讨拉米夫定联合低剂量乙型肝炎（乙肝）免疫球蛋白（HBIG）预防肝移植术后乙肝复发的效果及乙肝复发后的治疗。方法对2000年12月至2003年5月因乙肝相关性终末期肝病和（或）合并肝细胞癌于我院接受肝移植手术并经随访的11例患者进行回顾性分析。所有患者均接受拉米夫定联合低剂量HBIG预防乙肝复发方案。观察术后近期乙肝转阴情况、术后较远期乙肝复发情况以及乙肝复发后的治疗情况。结果（1）所有患者HBsAg、HBeAg、HBV-DNA均于术后1-4d转为阴性,术后1周所有患者对HBIG均有反应,HBsAb滴度水平逐渐上升;（2）所有患者于观察期内生存情况均良好,对患者HBsAb滴度水平定期进行监测结果示大部分患者HBsAb滴度水平与预期治疗水平基本符合;（3）1例患者于术后25个月乙肝复发,通过改用阿德弗韦并加大HBIG用量,基本得到控制。结论拉米夫定联合低剂量HBIG预防肝移植后乙肝复发疗效确切,而且可显著降低治疗费用。     

拉米夫定联合乙肝免疫球蛋白防治肝移植术后乙肝复发的多中心临床研究

目的研究拉米夫定联合乙肝免疫球蛋白防治肝移植术后乙肝复发的效果。方法自2004年5月～2005年10月,采用随机、阳性药物平行对照、多中心临床研究的方法,在9家医院对230例病人进行了研究。结果在有效病例,在同等剂量给药的条件下,HBIG对靶抗原HBsAg的中和量及术后7天内HBsAg阴转率的变化趋势充分体现了HBIG的量效、时效性及给药途径不同存在的量效、时效区别。在联合使用拉米夫定时,HBIG剂量若定为无肝期至术后HBV标志物转阴前HBsAb效价维持在300IU/L,HBV标志物转阴后效价维持在100IU/L似乎更科学,间隔4周给药可维持体内相对稳定的药物浓度。观察到的不良事件与HBIG无关,无效病例可能与乙肝病毒变异有关。结论拉米夫定联合乙肝免疫球蛋白防治肝移植术后乙肝复发的方案是安全、有效的。     

慢性肾脏病患者接种乙肝疫苗疗效研究

目的:探讨慢性肾脏病(chronic kidney disease,CKD)早中期(CKD1~3期)、晚期(CKD4~5期)患者接种乙肝疫苗后的反应情况,明确CKD患者接种乙肝疫苗的最佳时期,使CKD患者产生主动免疫抵御HBV感染。方法:对乙肝两对半全阴性的慢性肾脏病早中期、晚期患者接种乙肝疫苗,观察两组患者乙肝表面抗体的阳转率及抗体滴度高低情况,同时,将CKD早中期组分为接受或未接受激素/免疫抑制剂两组,所有CKD患者再分为男性、女性两组,分别对上述分组进行比较,观察各组患者乙肝表面抗体的阳转率及抗体滴度高低情况。结果:(1)CKD早中期患者接种乙肝疫苗后,乙肝表面抗体阳转率明显高于CKD晚期患者,且抗体滴度明显高于CKD晚期组。(2)在CKD早中期组中接受或未接受激素/免疫抑制剂治疗的患者中抗体阳转率差异无统计学意义,但接受激素/免疫抑制剂组抗体滴度更高。(3)性别不是影响乙肝疫苗接种效果的因素。结论:CKD早中期患者接种乙肝疫苗疗效优于CKD晚期患者,激素及免疫抑制剂治疗不影响CKD早中期患者接种乙肝疫苗的疗效,性别不影响接种效果。     

HBsAg阳性母亲其婴幼儿免疫阻断后无/低应答危险因素及个体化免疫干预效果分析

目的探讨HBsAg阳性母亲其婴幼儿免疫阻断后无/低应答的危险因素,以及个体化免疫干预的效果。方法选取2011年8月至2013年1月于本院出生母亲HBsAg阳性的婴幼儿144例,根据完成3次乙肝疫苗免疫计划后,即婴儿7月龄时的HBsAb水平,分为无/低应答组(53例)和正常应答组(91例)。分析两组母亲孕早期HBVDNA水平、HBV标志物(HBsAg、HBsAb、HBe Ag、HBe Ab和HBc Ab),婴儿出生史、喂养史以及出生后HBV标志物等,分析婴儿无/低应答的危险因素。选取乙肝疫苗全程免疫计划结束后无/低应答婴儿50例,正常应答婴儿50例作为对照组,对无/低应答婴儿进行个体化免疫干预,18月龄时比较两组患儿应答状态。结果 Logistic回归分析显示,早产儿、低出生体重儿、未按时添加蛋白质类辅食、未注射乙肝免疫球蛋白的儿童发生无/低应答的风险分别是正常儿童的25.51倍(Waldχ2=12.45)、20.54倍(Waldχ2=14.59)、28.47倍(Waldχ2=15.36)和16.67倍(Waldχ2=19.09)(P均0.001),母亲孕期e抗原、核心抗体是独立的危险因素,每增加1个单位,发生免疫不应答的风险分别增加1.001(Waldχ2=3.97)和1.16倍(Waldχ2=4.45)(P均0.05)。通过个体化免疫干预治疗,18个月龄时,83.3%的低应答儿和70.0%的无应答儿获得正常应答,与正常应答组差异无统计学意义(χ2=2.84、P=0.12;χ2=2.32、P=0.15),干预后低应答组的表面抗体水平与正常应答组差异无统计学意义(t=1.22、P=0.61),而无应答组抗体水平仍较正常组偏低(t=2.43、P=0.02)。与干预前相比,无应答组和低应答组的抗体水平均显著增高(t=2.54、P=0.02;t=2.76、P=0.01)。结论母亲孕期高水平HBe Ag、HBc Ab,早产儿、低出生体重儿、未按时添加蛋白质类辅食、未注射第2次乙肝免疫球蛋白是发生乙肝免疫无/低应答的危险因素。个体化免疫干预可有效提高免疫应答率,提高HBsAb水平,降低感染HBV的风险。     

湾里区15岁以下儿童乙肝感染和免疫状况调查

目的掌握湾里区15岁以下重点人群乙肝感染和免疫状况,为制定15岁以下儿童乙肝防治策略提供可靠的依据。方法采用酶联免疫法对3 128名1～15岁乙肝表面抗原携带情况进行调查分析,以问卷和查验预防接种证或卡片的方式对乙肝疫苗接种率进行调查。结果 3 128名儿童中HBsAg阳性104名,阳性率为3.32%。合格接种乙肝疫苗2 438人,接种率为77.94%。结论 HBsAg携带率随年龄增长而逐渐上升。乙肝疫苗的接种率随着年龄的增长逐渐降低。合格接种乙肝疫苗接种是阻断乙肝传播的有效途径,今后需提高乙肝疫苗的合格接种率,重点在大年龄组（6岁以上）儿童中开展乙肝疫苗查漏补种工作,加强乙肝防治知识的宣传,实现15岁以下重点人群乙肝表面抗原携带率3%以下目标。     

肝移植术后受者接种新型冠状病毒灭活疫苗单中心回顾性研究

目的探讨肝移植受者术后接种新型冠状病毒灭活疫苗(以下简称新冠疫苗)的安全性。方法回顾性分析2003年3月至2019年10月于解放军总医院第五医学中心行肝移植术、术后病情稳定并完成新冠疫苗接种疗程的151例受者的临床资料。统计接种新冠疫苗后受者出现接种部位疼痛, 疲惫感, 头晕头痛, 皮肤瘙痒等的频次。按接种疫苗后有无出现局部及全身反应进行安全性对比分析。同时, 按照疫苗生产企业是北京科兴中维生物技术有限公司(以下简称北京科兴)还是国药集团中国生物北京生物制品研究所有限责任公司(以下简称北京生物), 将完整接种了同一公司2剂疫苗的受者分为北京科兴组和北京生物组;按受者年龄是否大于60岁, 将其分为≥60岁组与<60岁组, 对各组肝移植受者术后接种新型冠状病毒灭活疫苗的安全性进行对比分析。结果本研究151例受者中, 年龄<60岁者98例(<60岁组), ≥60岁者53例(≥60岁组);疫苗接种距离肝移植手术的中位时间为8.44(4.37, 12.39)年;血清中位他克莫司浓度为2.5(1.8, 3.9)ng/L。完整接种了2剂北京科兴生产的新冠疫苗的有83例(北京科兴组)...     

Short-term high-dose followed by long-term low-dose hepatitis B immunoglobulin and lamivudine therapy prevented recurrent hepatitis B after liver transplantation

Hepatitis B immunoglobulin (HBIg) and lamivudine combination has been accepted as the best way to control hepatitis B recurrence after liver transplantation. However, the optimal dose of HBIg and the target titer of hepatitis B surface antibody (HBsAb) remain unclear. We report our satisfactory experience with high-dose HBIg in the early period followed by low-dose HBIg with lamivudine. Subjects comprised five patients with fulminant hepatitis (FH) and 18 patients with liver cirrhosis (LC) who underwent liver transplantation. HBIg at a dosage of 200 IU/kg per day was administered for one week postoperatively. Thereafter, HBIg was administered only for HBsAb titer <100 IU/L. After six months, HBIg was withdrawn in FH and administered in LC only for HBsAb titer <10 IU/L. Lamivudine was administered to two FH and all LC cases. Although two patients with LC showed transient hepatitis B surface antigen (HBsAg) recurrence, all patients remained HBsAg-negative at the final follow-up date. This method allows reliable and cost-effective control of hepatitis B recurrence.     

Good response to HBsAg vaccine in dialysis patients is associated with high CD4+/CD8+ ratio

Objective

Chronic renal failure is accompanied by various abnormalities of innate and acquired, cellular and humoral immunity. We aimed to investigate whether positive Candida skin test results, CD4+ and CD8+, before the first dose of vaccination could be a predictor for antibody response to hepatitis B vaccination and the relation of these parameters with hepatitis B antibody levels 1?month after the last dose of vaccination.

Materials and methods

The present study was carried out in 57 dialysis patients. All patients received recombinant hepatitis B vaccine (40???g) given intramuscularly in the deltoid muscle in a four-dose schedule at 0, 1, 2, and 6?months. Candida skin test and lymphocyte subsets (CD4+ and CD8+) were determined before the first dose of vaccination and 1?month after the fourth inoculation of hepatitis B vaccine.

Results

Ten patients (17.5%) were non-responders (HBsAb??100?IU/L), which was determined 1?month after the fourth dose of vaccination. Thirty-nine patients (68.4%) and 44 patients (77.2%) were anergic to Candida skin test before the first dose and 1?month after fourth inoculation of hepatitis B vaccine, respectively. There was no relationship between Candida skin test and response to hepatitis B vaccination. Mean age was lower, and CD4+/CD8+ ratio measured both before and after vaccination was higher in good responders compared with that of weak responders and that of non-responders. Females were better responders than males.

Conclusion

High skin test anergy rate and low seroconversion rate after hepatitis B vaccination are important problems in patients on dialysis. Females, younger patients, and patients with higher CD4+/CD8+ ratio have better HBsAb antibody response to hepatitis B vaccination.     

Low-dose hepatitis B immunoglobulin given "on demand" in combination with lamivudine: a highly cost-effective approach to prevent recurrent hepatitis B virus infection in the long-term follow-up after liver transplantation

BACKGROUND: Cost of long-term prophylaxis with high-dose human hepatitis B immune globulin (HBIg) after liver transplantation is extremely high. The aim of the present study was to assess consumption rates of high (5,000 IU) and low (2,000 IU) doses of HBIg given intravenously "on demand", and determine their cost-effectiveness compared with conventional fixed monthly schedules. METHODS: The study included 11 male patients (mean age 53 years) who received transplants for hepatitis B virus (HBV)-related cirrhosis 29 to 96 months earlier, all receiving lamivudine (100 mg/day) prophylaxis. Each patient received three consecutive intravenous infusions of 5,000 IU HBIg, followed by three 2,000 IU infusions. HBIg consumption was assessed by serial measurement of serum hepatitis B surface antibody (HBsAb) titer at 2-week intervals. HBIg was readministered only when HBsAb titers dropped below 70 IU/L (i.e., "on demand"). RESULTS: Mean HBsAb peak titers after high and low HBIg doses were 1,641 +/- 385 and 848 +/- 216 IU/L, respectively (P <0.0001). Mean time to reach an HBsAb titer less than 70 IU/L was 79.5 +/- 38.2 days versus 61.6 +/- 32.1 days, respectively (P =NS). Interindividual variation coefficients were 23 +/- 18% and 32 +/- 26% (5,000 IU and 2,000 IU, respectively). Using the on demand approach, maintenance of a protective anti-HBs titer required an average number of 4.0 (5,000 IU) and 5.6 (2,000 IU) HBIg administrations per year, respectively (P =NS). CONCLUSIONS: Individual HBIg consumption profiles are highly variable. A low-dose (2,000 IU) on demand HBIg administration schedule is highly cost-effective and provides more than 50% savings compared with conventional high-dose monthly schedules.     

肝移植术后HBV再感染的危险因素分析及对策

目的探讨肝移植术后乙型肝炎病毒(HBV)再感染的危险因素及相关对策。方法对2003年9月至2004年12月间在我院施行原位肝移植术病例进行前瞻性研究,选取符合研究标准的130例患者,采用肌注型乙型肝炎免疫球蛋白(HBIg)联合核苷类抗病毒药物预防HBV再感染,并长期随访,分析HBV再感染的危险因素。结果130例中128例术后血清HBsAg转为阴性,并检测到HBsAb,平均随访12.2个月,HBV再感染率为6.3%(8/128)。结论肝移植术前血清HBeAg阳性、术后第1天血清HBsAg阳性及HBsAb<200U/L是HBV再感染的危险因素。     

Failure of hepatitis B vaccination with conventional HBsAg vaccine in patients with continuous HBIG prophylaxis after liver transplantation.

Hepatitis B vaccination after liver transplantation for hepatitis B-related liver disease has been investigated as an alternative strategy to reinfection prophylaxis with hepatitis B immunoglobulin (HBIG) with conflicting results. In most studies, HBIG treatment was discontinued before vaccination. An outstanding good response was achieved with vaccination under continuous HBIG administration using hepatitis B surface antigen (HBsAg)-based vaccine containing special adjuvants. Both, adjuvants and continuous HBIG administration have been discussed as crucial factors for good response. Twenty-four patients were vaccinated with conventional double dose recombinant vaccine containing 40 microg HBsAg up to 12 times at weeks 0, 2, 4 (cycle 1), 12, 14, 16 (cycle 2), 24, 26, 28 (cycle 3), and 36, 38, 40 (cycle 4). All patients received 2,000 IU HBIG every 6 weeks (4 times intravenously and 4 times intramuscularly). A significant response was defined as reconfirmed increase of anti-HBs-antigen (anti-HBs) unexplained by HBIG administration or lack of anti-HBs decrease below 100 IU/L after discontinuation of HBIG treatment after week 48. Only 2 of 24 patients (8.3%) responded significantly. Anti-HBs started to increase after the seventh vaccination (cycle 3, during intramuscular HBIG administration) in 1 patient and after 12th vaccination (cycle 4, during intravenous HBIG administration) in the other. Maximum anti-HBs levels were >1,000 IU/L in both patients and decreased significantly slower as compared to passive prophylaxis during follow-up. In conclusion, the conventional HBsAg vaccine failed to induce a significant humoral immune response in most patients despite continued HBIG treatment. Further studies should address the question, of whether the use of potent adjuvant systems results in higher response rates.     

Case studies in orthotopic liver transplantation for hepatitis B: a panel discussion

Five cases that were referred to the Division of Transplantation at NYU School of Medicine for consideration for liver transplantation were discussed among a panel of hepatitis B and liver transplant experts. Opinions were obtained on the management at every stage of treatment of patients with the following initial information: Case one: young Asian woman in stage IV hepatic coma; intubated; prothrombin time (PT): 30 s; serum glutamic oxaloacetic transaminase (SGOT): 8,000 IU; total bilirubin: 25 mg/dL; hepatitis B surface antigen (HBsAg) positive. Case two: 70-yr-old woman, native of Greece; decompensated cirrhosis with encephalopathy; Child-Pugh Class C; HBsAg positive; hepatitis B surface antibody (HBsAb) negative; hepatitis B e antigen (HBeAg) positive; hepatitis B e antibody (HBeAb) negative; hepatitis B virus (HBV) DNA titer: 10,000. Case three: Muscular detective working full-time; cirrhosis; Child Pugh Class B; ascites controlled with spironolactone and furosemide; PT: 19s; HBsAg positive; HBsAb negative; HBV DNA titer: 50,000; low platelet count. Case four: 45-yr-old baker; cirrhosis and resectable 4-cm hepatoma; Child-Pugh Class B; PT: 16 s; Blood type O; United Network for Organ Sharing (UNOS) 2B; HBV DNA titer: 3,000. Case five: 40-yr-old Indian man; 300 pounds with massive ascites; Child Pugh Class C; PT: 17 s; HBsAg positive; HBV DNA titer: 22,000; transplanted with intra-operative hypotension; tacrolimus; graft functioning; HBIg 10,000 IU intra-operative and around the clock during the first post-operative week; required huge doses of hepatitis B immune globulin (HBIg) to maintain adequate HBsAb level; daily loss of 5 6 L of ascites fluid; post-operative day 8: anuric, blood urea nitrogen (BUN) 127, creatinine 3, mental status changes.     

Long-term results of hepatitis B immunoglobulin and lamuvidine for hepatitis B prophylaxis after liver transplantation

Purpose

Recurrence of hepatitis B virus after a liver transplantation (OLT) is a risk factor affecting graft and patient survivals. Short-term hepatitis B virus reactivation rates after OLT range between 3% and 15%. Using combination prophylaxis, the outcomes of OLT among patients with liver disease related to hepatitis B virus have improved to levels comparable to those whose disease is not related to hepatitis B virus.

Materials and Methods

Since September 2001, we performed 288 OLT in 282 patients including 74 who had liver failure related to hepatitis B virus among whom 58 were followed for >12 months and analyzed retrospectively. Our protocol included lamivudine (100 mg orally per day beginning the day after surgery) and hepatitis B immunoglobulin (10,000 IU IV during the anhepatic phase, 2000 IU/d IV during the first week after surgery, 2000 IU IV/month from postoperative months 1 to 12). Using our protocol, the anti-hepatitis B surface antibodies (HBsAb) serum titer was maintained up to 100 IU/mL. The female:male ratio was 11:47. The mean age of patients was 43 ± 12.8 years.

Results

Five patients died of causes unrelated to hepatitis B virus. At the time of death, their hepatitis B surface antigens were negative, and serum titers of anti-HBsAb were 45, 35.3, 56.4, 79.6, and 123 IU/mL. Mean follow-up was 46.5 ± 18.9 months (range, 12-79). The hepatitis B surface antigen became positive in 4 patients; the remaining 49 had no evidence of hepatitis B surface antigen. In 18 patients, serum titer of anti-hepatitis B surface antigen was 0; in the remaining 31 patients, it was 69.2 ± 133 IU/mL.

Conclusion

Our combination protocol with hepatitis B immunoglobulin and lamivudine is a safe, cost-saving, and effective treatment for hepatitis B virus prophylaxis after liver transplantation.     

Immunization with an adjuvant hepatitis B vaccine in liver transplant recipients: antibody decline and booster vaccination with conventional vaccine.

Patients after orthotopic liver transplantation (OLT) due to hepatitis B virus (HBV)-related disease are at risk of endogenous hepatitis B reinfection and may receive life long prophylaxis with hepatitis B hyperimmunoglobulin (HBIG). In a previous study 16 of 20 OLT patients were immunized successfully with an adjuvant hepatitis B vaccine. To maintain protective antibody levels under immunosuppressive therapy, 11 of these patients were revaccinated with a double dosed conventional hepatitis B vaccine. Median interval between last vaccination and booster was 24 months (range 22-31 months). Antibody titres against hepatitis B surface antigen (anti-HBs) were monitored at the day of booster vaccination (day 0), at day 7 and day 28. At day 0, all vaccinees but one had anti-HBs titres greater than 500 IU/L (median 1,925 IU/L, range 196-7,612 IU/L). Maximum antibody titres after previous vaccination declined by a median of 82% (range 47-96%). After booster vaccination the anti-HBs titre increased significantly by a median factor of 2.42 (P<0.05). In conclusion, the majority of liver transplant recipients who previously had responded to adjuvant hepatitis B vaccine exhibited sufficient immunocompetence to produce a substantial antibody response after booster immunization with a conventional vaccine.     

Low-dose intramuscular hepatitis B immune globulin and lamivudine for long-term prophylaxis of hepatitis B recurrence after liver transplantation

The combination of lamivudine and hepatitis B immunoglobulins (HBIg) to prevent recurrence of HBV hepatitis has significantly improved the survival of patients transplanted for HBV-related end-stage liver disease. Generally, HBIg are administered intravenously. We evaluated the efficacy, tolerability, and cost savings of long-term intramuscular HBIg and lamivudine in 28 patients (23 men and 5 women), who received liver transplants for acute or chronic HBV-related liver disease. Twelve patients started lamivudine before and 16 at the time of liver transplantation. HBIg were administered intravenously during the first week (50 to 70,000 IU) and intramuscularly thereafter (1200 IU every 3 to 6 weeks) to maintain an HbsAb titer >100 IU/L. Mean follow-up was 20 +/- 13 months. Only one patient experienced HBV recurrence (9 months after transplantation). This patient had failed to follow the scheduled prophylaxis. Cumulative survival at 3 years was 83%. Intramuscular HBIg were well tolerated in all cases. Cost analysis comparing intramuscular vs intravenous HBIg administration showed that 39,490 Euros were saved per patient per year. These preliminary results show that low-dose intramuscular HBIg and lamivudine are efficacious and cost-effective for long-term prophylaxis of hepatitis B recurrence after liver transplantation.