Sussman N L, Chong M G, Koussayer T, He D E, Shang T A, Whisennand H H, Kelly J H
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Hepatology. 1992 Jul;16(1):60-5. doi: 10.1002/hep.1840160112.
Liver transplantation is currently the only effective therapy for patients with fulminant hepatic failure. The availability of an artificial liver could bridge these patients through the relatively brief crisis period and allow their own livers to regenerate, providing a more favorable outcome and sparing the trauma and expense of transplant. We have developed a device consisting of a highly differentiated human liver cell line cultured in a hollow fiber cartridge. This device is capable of supporting dogs with acetaminophen-induced fulminant hepatic failure for a period long enough for their own livers to resume function. Even though liver function tests such as albumin and prothrombin time became extremely abnormal during the course of the experiment, the dogs did not become encephalopathic. Two of the three treated animals recovered sufficient liver function after 42 to 48 hr of treatment that they could be disconnected from the device, and they survived the experiment. Histological results and serum ALT levels suggest that the device affected the course of the disease in two animals, allowing recovery of hepatocytes that would otherwise have lysed. In the third animal, regenerative nodules demonstrated that, even in the presence of severe liver injury, the device was capable of supporting total liver function.
肝移植目前是暴发性肝衰竭患者唯一有效的治疗方法。人工肝的应用可以帮助这些患者度过相对短暂的危险期,使他们自身的肝脏得以再生,从而获得更好的治疗效果,并避免移植带来的创伤和费用。我们研发了一种装置,它由在中空纤维盒中培养的高度分化的人肝细胞系组成。该装置能够支持因对乙酰氨基酚诱导的暴发性肝衰竭的犬类,支持时间足够长,使其自身肝脏恢复功能。尽管在实验过程中,诸如白蛋白和凝血酶原时间等肝功能测试变得极其异常,但这些犬类并未出现肝性脑病。三只接受治疗的动物中有两只在治疗42至48小时后恢复了足够的肝功能,从而可以与该装置分离,并在实验中存活下来。组织学结果和血清谷丙转氨酶水平表明,该装置对两只动物的病程产生了影响,使原本会裂解的肝细胞得以恢复。在第三只动物中,再生结节表明,即使存在严重的肝损伤,该装置仍能够维持肝脏的整体功能。