A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients
A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients
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DOI：
10.1002/lt.20405
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发表时间：
2005-08-01
影响因子：
4.6
通讯作者：
Gnann, JW
中科院分区：
文献类型：
--
作者：
Davis, GL;Nelson, DR;Gnann, JW
慢性丙型肝炎是肝移植最常见的适应证，但病毒复发普遍存在，且大多数受者会发生移植物进行性损伤。我们的目的是评估高剂量的人丙型肝炎抗体富集免疫球蛋白产品（HCIG）在因慢性丙型肝炎接受肝移植的患者中的安全性、药代动力学（PK）和抗病毒效果。这是一项在美国4个移植中心进行的多中心、随机、开放标签、对照试验。共有18例接受肝移植的慢性丙型肝炎患者被随机分为接受低剂量HCIG（75mg/kg）、高剂量HCIG（200mg/kg）或不接受治疗三组。根据肝移植受者中抗乙型肝炎免疫球蛋白的药代动力学，采用时间依赖性给药策略，在14周内对每位接受治疗的患者共进行17次HCIG输注。在整个研究期间连续获取丙型肝炎病毒水平、肝酶和肝活检结果。在第4、10和98天测定HCV抗体的药代动力学特征。HCIG输注是安全且可耐受的。由于18% - 30%的剂量会出现症状，输注速度无法达到最大。移植后HCIG的半衰期极短，但逐渐延长。在高剂量组中，大多数受试者的血清丙氨酸氨基转移酶（ALT）水平恢复正常，且无患者发生肝纤维化。然而，两种剂量下血清HCV RNA水平均未被抑制。总之，HCIG这种抗 - HCV富集免疫球蛋白产品在接受肝移植的慢性丙型肝炎患者中似乎是安全的。需要进一步研究以确定该药物在这类患者中是否具有有益效果。
Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALI) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.