Sauer I M, Kardassis D, Zeillinger K, Pascher A, Gruenwald A, Pless G, Irgang M, Kraemer M, Puhl G, Frank J, Müller A R, Steinmüller T, Denner J, Neuhaus P, Gerlach J C
General, Visceral and Transplantation Surgery, Charité--Campus Virchow Klinikum, Humboldt-University Berlin, Berlin, Germany.
Xenotransplantation. 2003 Sep;10(5):460-9. doi: 10.1034/j.1399-3089.2003.00062.x.
The objective of this study was to evaluate the feasibility and safety of a hybrid liver support system with extracorporeal plasma separation and bioreactor perfusion in patients with acute liver failure (ALF) who had already fulfilled the criteria for high urgency liver transplantation (LTx). Eight patients (one male, seven female) were treated in terms of bridging to transplantation. The mean age was 36.5 yr (range 20 to 58). Etiology of liver failure was drug-related in two patients, hepatitis B infection in three patients, and unknown for three patients. The bioreactors were charged with primary liver cells from specific pathogen-free pigs. Cell viability varied between 91 and 98%. Continuous liver support treatment over a period of 8 to 46 h (mean 27.3 h) was safely performed and well-tolerated by all patients. No complications associated with the therapy were observed during the follow-up period. Thrombocytopenia was considered to be an effect of the plasma separation. Subsequently, all patients were transplanted successfully and were observed over at least 3 yr with an organ and patient survival rate of 100%. Screening of patient's sera for antibodies specific for porcine endogenous retroviruses (PERVs) showed no reactivity--either prior to application of the system, or after extracorporeal treatment. The results encourage us to continue the development of the technology, and further studies appear to be justified. The bioreactor technology has been integrated into a modular extracorporeal liver support (MELS) system, combining biologic liver support with artificial detoxification technology.
本研究的目的是评估一种具有体外血浆分离和生物反应器灌注功能的混合肝支持系统在已符合高紧迫性肝移植（LTx）标准的急性肝衰竭（ALF）患者中的可行性和安全性。8例患者（1例男性，7例女性）接受了桥接移植治疗。平均年龄为36.5岁（范围20至58岁）。肝衰竭的病因在2例患者中与药物相关，3例患者为乙型肝炎感染，3例患者病因不明。生物反应器接种了来自无特定病原体猪的原代肝细胞。细胞活力在91%至98%之间。所有患者均安全地接受了为期8至46小时（平均27.3小时）的持续肝支持治疗，且耐受性良好。随访期间未观察到与治疗相关的并发症。血小板减少被认为是血浆分离的结果。随后，所有患者均成功接受移植，并至少观察了3年，器官和患者生存率均为100%。对患者血清进行猪内源性逆转录病毒（PERV）特异性抗体筛查，结果显示在应用该系统之前或体外治疗后均无反应性。这些结果鼓励我们继续开发该技术，进一步的研究似乎是合理的。生物反应器技术已被整合到模块化体外肝支持（MELS）系统中，将生物性肝支持与人工解毒技术相结合。
