al-Hemsi B, McGory R W, Shepard B, Ishitani M B, Stevenson W C, McCullough C, Pruett T L
Department of Surgery, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Clin Transplant. 1996 Dec;10(6 Pt 2):668-75.
Aggressive administration of hepatitis B immune globulin (HBIg) has been shown to prevent hepatitis B viral (HBV) infection of the allograft; however, the clinical sequela of such therapy has not been previously described. We reviewed our experience with high dose, intravenous infusion of an intramuscular HBIg preparation to assess the effectiveness and complications of such therapy. Thirty three orthotopic liver transplants (OLTx) were performed in 32 patients with chronic HBV cirrhosis at the University of Virginia between March 1990 and June 1995. Twenty-nine of 32 (91%) patients remain free of HBV recurrence (defined by undetectable serum HBsAg and HBV-DNA) after a mean of 21 months (2-54 months), with one patient requiring retransplantation. Three (10%) patients died of non-HBV causes (two vascular events, one infectious event). Twenty episodes of acute cellular rejection were treated in 18 patients (two had two episodes). Sixteen rejections occurred within 18 d of transplant, 19 by day 120, and one late rejection occurred at 18 months owing to medication non-compliance. Eighteen patients had at least one documented infection. Six patients were treated for CMV infection (five empirically). Eight patients were treated for HSV infections (seven mild herpetic labialis and one herpetic keratitis). Four patients had documented fungal infection (one mucormycosis pneumonia and three minor superficial mucosal infections). With the exception of one necrotizing pneumonia, 11 bacterial infections were successfully treated with conventional antimicrobial agents. No patient developed post-transplant lymphoproliferative disorder. Symptoms associated with HBIg infusion were intermittent but frequent and consisted of myalgias, predominantly back pain (90%), headache (20%) and flushing (5%). No patient experienced anaphylaxis, fever, rash, arthritis or hypotension. Despite the potential for mercury toxicity and HCV transmission in the HBIg formulations currently available in the United States, serum mercury levels remained below standards for industrial exposure (60 micrograms/ml), and only one individual developed post-transplant HCV infection after receiving multiple units of unscreened blood prior to 1991.
High-dose HBIg prevented HBV infection of the allograft in 29 of 32 patients transplanted for HBV cirrhosis with three non-HBV associated deaths. The intravenous infusion of HBIg was frequently associated with minor side effects that were safely tolerated by patients. The risk of HCV transmission and mercury toxicity are minimal, but support the need for a new intravenous formulation of HBIg. HBIg therapy successfully decreased post-OLTx HBV recurrence with no clinical events associated with immunosuppression. Patients did non experience allergic or infusion-related complications that altered or terminated therapy. Manufacturing modifications of HBIg may allow for improved patient tolerance and decreased risks.
已证明积极给予乙肝免疫球蛋白（HBIg）可预防同种异体移植肝的乙肝病毒（HBV）感染；然而，此前尚未描述过这种治疗的临床后遗症。我们回顾了高剂量静脉输注肌肉注射用HBIg制剂的经验，以评估这种治疗的有效性和并发症。1990年3月至1995年6月期间，弗吉尼亚大学对32例慢性HBV肝硬化患者进行了33例原位肝移植（OLTx）。32例患者中有29例（91%）在平均21个月（2 - 54个月）后仍无HBV复发（定义为血清HBsAg和HBV - DNA检测不到），其中1例患者需要再次移植。3例（10%）患者死于非HBV相关原因（2例血管事件，1例感染事件）。18例患者发生了20次急性细胞排斥反应（2例患者发生了2次）。16次排斥反应发生在移植后18天内，19次在120天内，1次晚期排斥反应发生在18个月，原因是患者未遵医嘱服药。18例患者至少有1次记录在案的感染。6例患者接受了巨细胞病毒感染治疗（5例经验性治疗）。8例患者接受了单纯疱疹病毒感染治疗（7例轻度唇疱疹，1例疱疹性角膜炎）。4例患者有记录在案的真菌感染（1例毛霉菌肺炎，3例轻度浅表黏膜感染）。除1例坏死性肺炎外，11例细菌感染用传统抗菌药物成功治疗。没有患者发生移植后淋巴细胞增殖性疾病。与HBIg输注相关的症状是间歇性但频繁出现的，包括肌痛，主要是背痛（90%）、头痛（20%）和潮红（5%）。没有患者发生过敏反应、发热、皮疹、关节炎或低血压。尽管美国目前可用的HBIg制剂存在汞中毒和丙型肝炎病毒传播的可能性，但血清汞水平仍低于工业暴露标准（60微克/毫升），并且只有1例个体在1991年之前接受多单位未筛查血液后发生了移植后丙型肝炎病毒感染。
高剂量HBIg预防了32例因HBV肝硬化接受移植患者中29例的同种异体移植肝HBV感染，有3例非HBV相关死亡。静脉输注HBIg经常伴有轻微副作用，患者可安全耐受。丙型肝炎病毒传播和汞中毒的风险极小，但支持需要一种新的静脉用HBIg制剂。HBIg治疗成功降低了OLTx后HBV复发，没有与免疫抑制相关的临床事件。患者没有经历改变或终止治疗的过敏或输注相关并发症。HBIg的生产改进可能会提高患者耐受性并降低风险。
