Bilir B M, Guinette D, Karrer F, Kumpe D A, Krysl J, Stephens J, McGavran L, Ostrowska A, Durham J
Department of Medicine, University of Colorado School of Medicine and the Children's Hospital, Denver, CO, USA.
Liver Transpl. 2000 Jan;6(1):32-40. doi: 10.1002/lt.500060113.
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 III 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.
大多数急性肝衰竭（ALF）患者在等待原位肝移植（OLT）的过程中死亡。尚无其他治疗方式被证明可提高生存率。本研究旨在评估肝细胞移植（HT）的安全性和可行性，以及供体细胞随后的植入和功能。通过其形态特征、P - 4501A1转录的诱导以及通过异种移植到大鼠体内后的体内存活情况，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了脾内（4例患者）和/或肝内（2例患者）HT。所有患者均有III至IV级脑病，因子V水平低于0.5 U/mL，依赖呼吸机和透析，且不是OLT的候选者。HT后存活48小时的5例患者中有3例在脑病评分、动脉血氨水平和凝血酶原时间方面有显著改善。临床改善伴随着氨基比林和咖啡因清除率的增加。根据HT后的临床经验，所有3例患者的存活时间均大大超过预期（分别为12天、28天和52天），但最终均死亡。尸检通过光学显微镜和荧光原位杂交（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，会出现一些可接受但明确的并发症。通过经颈静脉活检和尸检的组织学检查及FISH证明了供体肝细胞的植入。脑水肿、脑病分级以及安替比林和咖啡因清除率的改善表明了肝细胞的功能，尽管移植后有24至72小时的延迟。
