Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients
Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients
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DOI：
10.1177/039139880202500305
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发表时间：
2002-03-01
影响因子：
1.7
通讯作者：
Pinna, AD
中科院分区：
文献类型：
--
作者：
Morsiani, E;Pazzi, P;Pinna, AD
原位肝移植（奥尔特）是治疗严重急性肝功能衰竭（AHF）的唯一有效方法。移植器官的稀缺导致对AHF患者进行临时肝脏支持治疗的迫切需要。基于肝细胞的生物人工肝（BAL）正在研究中，其主要目的是作为桥接治疗，直到肝脏可用于奥尔特或促进自发性肝再生。我们开发了一种新的径向流生物反应器（RFB）的三维，高密度肝细胞培养和一个集成的泵装置，其中，血浆置换后，患者的血浆通过肝细胞填充的RFB再循环。将230 g新鲜分离的猪肝细胞加载到RFB中用于临床肝脏支持治疗。对7例Ⅲ ~ Ⅳ度昏迷等待紧急肝奥尔特的急性肝衰竭患者进行了8次BAL治疗。3例无既往肝病史的患者因B型肝炎病毒引起暴发性肝功能衰竭（FHF），3例因移植肝原发性无功能（PNF），1例因既往腹部外伤和肝脏手术引起AHF。7例患者中有6例在BAL治疗后接受奥尔特，持续6-24小时。所有患者均耐受良好，如脑病水平改善、血清氨、转氨酶降低和凝血酶原时间改善所示，奥尔特后神经功能完全恢复。我们的初步临床经验证实了这种BAL配置的安全性，并表明其作为AHF患者临时肝脏支持系统的临床疗效。
Orthotopic liver transplantation (OLT) is the only effective therapeutic modality in severe acute hepatic failure (AHF). The scarcity of organs for transplantation leads to an urgent necessity for temporary liver support treatments in AHF patients. A hepatocyte-based bioartificial liver (BAL) is under investigation with the main purpose to serve as bridging treatment until a liver becomes available for OLT or to promote spontaneous liver regeneration. We developed a novel radial-flow bioreactor (RFB) for three-dimensional, high-density hepatocyte culture and an integrated pumping apparatus in which, after plasmapheresis, the patient's plasma is recirculated through the hepatocyte-filled RFB. Two hundred thirty grams of freshly isolated porcine hepatocytes were loaded into the RFB for clinical liver support treatment. The BAL system was used 8 times in supporting 7 AHF patients in grade III-IV coma, all waiting for an urgent OLT Three patients with no history of previous liver diseases were affected by fulminant hepatic failure (FHF) due to hepatitis B virus, 3 by primary non-function (PNF) of the transplanted liver, and one by AHF due to previous abdominal trauma and liver surgery. Six out of 7 patients underwent OLT following BAL treatment(s), which lasted 6-24 hours. All patients tolerated the procedures well, as shown by an improvement in the level of encephalopathy, a decrease in serum ammonia, transaminases and an amelioration of the prothrombin time, with full neurological recovery after OLT Our initial clinical experience confirms the safety of this BAL configuration and suggests its clinical efficacy as a temporary liver support system in AHF patients.