Hepatocyte transplantation in acute liver failure
Hepatocyte transplantation in acute liver failure
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DOI：
10.1016/s1527-6465(00)80030-1
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发表时间：
2000-01-01
影响因子：
4.6
通讯作者：
Durham, J
中科院分区：
文献类型：
--
作者：
Bilir, BM;Guinette, D;Durham, J
大多数急性肝衰竭（ALF）患者在等待原位肝移植（OLT）时死亡，没有其他治疗方式被证明可以提高生存率。本研究旨在评估肝细胞移植（HT）的安全性和可行性以及随后的移植和供体细胞的功能。通过形态学特征、P-4501A1转录诱导和异种移植在大鼠体内的存活来评估冷冻保存和解冻的人肝细胞的功能和结构完整性。5例严重ALF患者在环孢素免疫抑制下通过血管造影接受脾内（4例）和/或肝内（2例）HT治疗，所有患者均为病至IV级脑病，因子V水平低于0.5 U/mL，依赖呼吸机和透析，不适合OLT治疗。在HT后48小时存活的5例患者中，有3例在脑病评分、动脉氨水平和凝血酶原时间方面有显著改善。临床改善与氨基比林和咖啡因清除率的增加是平行的。所有3例患者在接受HT治疗后的生存时间（12,28和52天）都比临床经验预期的要长得多，但最终死亡，尸检时光镜和荧光原位杂交（FISH）显示肝脏和脾脏中存在移植的肝细胞。冷冻保存和解冻的人肝细胞可以移植到ALF患者体内，但有一些可接受的并发症。经颈静脉活检和尸检的组织学检查和FISH证实了供体肝细胞的移植。脑水肿的改善、脑病等级的改善以及安替比林和咖啡因的清除提示功能，尽管移植后延迟24至72小时。版权所有(C) 2000年由美国肝病研究协会。
The majority of patients with acute liver failure (ALF) die waiting for orthotopic liver transplantation (OLT), No other treatment modality is shown to improve survival. This study was conducted to assess the safety and feasibility of hepatocyte transplantation (HT) and subsequent engraftment and function of donor cells. Functional and structural integrity of cryopreserved and thawed human hepatocytes were assessed by their morphological characteristics, induction of P-4501A1 transcription, and survival in vivo by xenotransplantation into rats. Five patients with severe ALF underwent intrasplenic (4 patients) and/or intrahepatic (2 patients) HT through angiography under cyclosporine immunosuppression, All patients had grade ill to IV encephalopathy and factor V levels less than 0.5 U/mL,were ventilator and dialysis dependent, and were not OLT candidates. Three of the 5 patients who survived 48 hours after HT had substantial improvement in encephalopathy scores, arterial ammonia levels, and prothrombin times. Clinical improvement was paralleled by an increase in aminopyrine and caffeine clearances. All 3 patients lived substantially longer than expected based on clinical experience after HT (12, 28, and 52 days) but eventually died, postmortem examination showed the presence of transplanted hepatocytes in liver and spleen by light microscopy and fluorescent in situ hybridization (FISH). Cryopreserved and thawed human hepatocytes can be transplanted into recipients with ALF with some acceptable but definite complications. Engraftment of donor hepatocytes was proven by histological examination and FISH by both transjugular biopsy and at autopsy. Improvement in brain edema, encephalopathy grade, and clearance of antipyrine and caffeine suggested function, albeit with a 24- to 72-hour delay posttransplantation. Copyright (C) 2000 by the American Association for the Study of Liver Diseases.