Morsiani E, Pazzi P, Puviani A C, Brogli M, Valieri L, Gorini P, Scoletta P, Marangoni E, Ragazzi R, Azzena G, Frazzoli E, Di Luca D, Cassai E, Lombardi G, Cavallari A, Faenza S, Pasetto A, Girardis M, Jovine E, Pinna A D
Department of Surgery, Sant'Anna University Hospital, University of Ferrara School of Medicine, Italy.
Int J Artif Organs. 2002 Mar;25(3):192-202. doi: 10.1177/039139880202500305.
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.
原位肝移植（OLT）是治疗严重急性肝衰竭（AHF）的唯一有效方法。可供移植的器官稀缺，这使得AHF患者迫切需要临时肝支持治疗。一种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，直至有肝脏可用于OLT，或促进肝脏自发再生。我们开发了一种新型径向流生物反应器（RFB）用于三维高密度肝细胞培养，并开发了一种集成泵送装置，在血浆置换后，患者的血浆通过充满肝细胞的RFB进行再循环。将230克新鲜分离的猪肝细胞加载到RFB中用于临床肝支持治疗。该BAL系统用于支持7例处于III-IV级昏迷的AHF患者，共使用了8次，所有患者均在等待紧急OLT。3例既往无肝脏疾病史的患者因乙型肝炎病毒导致暴发性肝衰竭（FHF），3例因移植肝原发性无功能（PNF），1例因既往腹部创伤和肝脏手术导致AHF。7例患者中有6例在接受BAL治疗（持续6-24小时）后接受了OLT。所有患者对治疗耐受性良好，表现为脑病程度改善、血清氨、转氨酶降低以及凝血酶原时间改善，OLT后神经功能完全恢复。我们最初的临床经验证实了这种BAL配置的安全性，并表明其作为AHF患者临时肝支持系统的临床疗效。
