Rozga J, Podesta L, LePage E, Morsiani E, Moscioni A D, Hoffman A, Sher L, Villamil F, Woolf G, McGrath M
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
Ann Surg. 1994 May;219(5):538-44; discussion 544-6. doi: 10.1097/00000658-199405000-00012.
To test the safety and efficacy of a bioartificial liver support system in patients with severe acute liver failure.
The authors developed a bioartificial liver using porcine hepatocytes. The system was tested in vitro and shown to have differentiated liver functions (cytochrome P450 activity, synthesis of liver-specific proteins, bilirubin synthesis, and conjugation). When tested in vivo in experimental animals with liver failure, it gave substantial metabolic and hemodynamic support.
Seven patients with severe acute liver failure received a double lumen catheter in the saphenous vein; blood was removed, plasma was separated and perfused through a cartridge containing 4 to 6 x 10(9) porcine hepatocytes, and plasma and blood cells were reconstituted and reinfused. Each treatment lasted 6 to 7 hours.
All patients tolerated the procedure(s) well, with neurologic improvement, decreased intracranial pressure (23.0 +/- 2.3 to 7.8 +/- 1.7 mm Hg; p < 0.005) associated with an increase in cerebral perfusion pressure, decreased plasma ammonia (163.3 +/- 21.3 to 112.2 +/- 9.8 microMoles/L; p < 0.01), and increased encephalopathy index (0.60 +/- 0.17 to 1.24 +/- 0.22; p < 0.03). All patients survived, had a liver transplant, and were discharged from the hospital.
This bioartificial liver is safe and serves as an effective "bridge" to liver transplant in some patients.
测试一种生物人工肝支持系统在严重急性肝衰竭患者中的安全性和有效性。
作者研发了一种使用猪肝细胞的生物人工肝。该系统在体外进行了测试，显示具有分化的肝功能（细胞色素P450活性、肝脏特异性蛋白合成、胆红素合成及结合）。在肝功能衰竭实验动物体内进行测试时，它提供了实质性的代谢和血流动力学支持。
7例严重急性肝衰竭患者在大隐静脉置入双腔导管；抽取血液，分离血浆并通过装有4至6×10⁹个猪肝细胞的柱进行灌注，然后将血浆和血细胞重新组合并回输。每次治疗持续6至7小时。
所有患者对该操作耐受性良好，神经功能改善，颅内压降低（从23.0±2.3降至7.8±1.7 mmHg；p<0.005），同时脑灌注压升高，血浆氨水平降低（从163.3±21.3降至112.2±9.8微摩尔/升；p<0.01），脑病指数升高（从0.60±0.17升至1.24±0.22；p<0.03）。所有患者均存活，接受了肝移植并出院。
这种生物人工肝是安全的，在某些患者中可作为肝移植的有效“桥梁”。
