原位肝移植加人工肝支持疗法治疗暴发性肝功能衰竭

目的 探讨原位肝移植加入人工肝支持疗法对暴发性肝功能衰竭的疗效及非生物型人工肝支持系统在暴发性肝功能衰竭肝移植术前准备中的作用。方法 本组7例暴发性肝功能衰竭患者,均有不同程度的肝昏迷,黄疸,腹水,肝功能损害,出血倾向,在等待供肝的过程中分别接受2-20次非生物型人工肝支持疗法,供肝到达后行原位肝移植术,结果 人工肝支持治疗后患者血清胆红素明显下降,腹水明显减少,部分病人肝性脑病有所好转,7例均顺利行肝移植,5例存活3-290个月,其中3例已存活1年半以上,并已恢复正常工作,2例术前有肝肾综合征者,术后3d死亡,其中1例并发急性重症胰腺炎。结论 原位肝移植加入工肝支持疗法是暴发性肝功能衰竭的有效方法,术前人工肝支持可作为暴发性肝功能衰竭等待供肝期间的桥梁,并可改善病情减少肝移植的危险因素。     

体外生物人工肝对无肝模型犬的支持效果

我们用悬浮高密度大量培养的肝细胞与中空纤维生物反应器及由血液透析仪改装的辅助循环装置共同构成一种体外生物人工肝支持系统（ＥＢＬＳＳ），对无肝模型犬进行人工肝支持实验，以期推动我国生物人工肝的研究，为肝衰竭的治疗开辟新的途径。一、材料与方法１．ＥＢＬＳ...     

生物人工肝支持系统的临床应用

回顾目前生物人工肝的研究现状及其临床成果。在Medline和其他图书馆数据库搜索关于生物人工肝及其临床试验的相关文献,根据各型生物反应器的特点和纳入临床试验的患者数对其结果进行分析。大约有10余种生物人工系统应用于临床,大部分结果显示出临床和生化指标的改善并证明是安全可行的。两种生物人工肝系统(ELAD和The Hepatassist System)进行了Ⅱ／Ⅲ期临床对照试验,虽没有取得预期生存率方面的改善,但在排除肝移植对患者生存率方面的影响后,接受The Hepatassist System治疗的急性和亚急性肝功能衰竭患者较未接受者生存率有明显改善(P=0．048)。相信在不久的将来,生物人工肝的治疗会有更进一步的发展和可喜的成果。     

生物人工肝的研究新进展

临床上暴发性肝功能衰竭（ｆｕｌｍｉｎａｎｔｈｅｐａｔｉｃｆａｉｌｕｒｅ，ＦＨＦ）十分常见，病死率高达７０％～８０％，其救治是亟待解决的难题〔１〕。由于此类患者发生肝细胞坏死及功能衰竭，依靠病因治疗及一般的内科支持治疗多不能代替肝细胞特异性功能，因此长...     

新型多层平板型生物人工肝体外支持系统治疗肝功能衰竭的临床研究

目的 评价新型多层平板型生物人工肝(BAL)体外支持系统治疗肝功能衰竭的临床效果及安全性.方法 2010年12月至2011年12月,有38例肝功能衰竭患者接受了新型多层平板型BAL治疗共计48例次,每次治疗时间为4h,于治疗前,治疗中,以及治疗后1、3、7和14d,抽取患者外周血监测肝功能和凝血功能等生化指标,并观察患者临床症状及体征的变化,以判定BAL的治疗效果.采用酶联免疫吸附试验法检测患者血浆及反应器中IgG、IgM及补体CH50的水平,采用聚合酶链反应检测外周血单个核细胞(PBMC)中猪内源性逆转录病毒(PERV) DNA、猪特异性细胞色素B(SsCytB)基因序列及逆转录酶的活性等,以评估BAL治疗的安全性.结果 大部分患者接受BAL治疗后感觉良好,精神状态、临床症状、各项指标较治疗前均有所缓解或明显改善,未发生严重不良反应.38例患者中,临床治愈9例,好转25例,治愈好转率为89.5％(34/38),治疗无效4例;有7例患者经BAL治疗后病情好转,顺利等到供肝接受了肝移植.治疗期间,患者血浆IgG、IgM和CH50水平均未出现明显变化,仅补体CH50在治疗1h时出现一过性下降,随后很快恢复正常水平;反应器内未检测出IgG,仅治疗4h时检出极少量IgG,治疗4h内均未检测出IgM.各时间点患者PBMC均未检测到PERV DNA,且患者血浆中均未检测到猪特异性SsCytB基因序列和逆转录酶活性.结论 新型多层平板型BAL体外支持系统对肝功能衰竭患者具有良好的临床治疗效果和安全性,其在患者等待供肝期间也可作为良好的过渡治疗手段.     

人工肝干预肝衰竭凝血项变化的研究

急性肝衰竭是一种复杂的多系统疾病,短期内可迅速出现凝血功能障碍和肝性脑病 等并发症,凝血功能障碍严重者可导致大量出血,是肝功能衰竭患者死亡的主要原因。目前急性肝衰竭 的治疗主要包括内科综合治疗、人工肝支持系统、肝移植三种方法。本文就人工肝支持系统治疗对肝功 能衰竭患者凝血项变化的影响做一综述。     

第五届国际暨全国肝衰竭与人工肝学术会议纪要

2009年1月20-22日,由中华医学会感染病学分会肝衰竭与人工肝学组、中国生物医学工程学会人工器官分会和中华临床感染病杂志主办的第五届国际暨全国肝衰竭与人工肝学术会议于在历史悠久的榕城福州顺利召开。本次大会为期3天,共收到论文149篇,其中专题报告25篇,有来自我国及美国、俄罗斯、澳大利亚、日本和印度尼西亚等国家的600余名相关专家和学者到会作了专题报告并进行了学术交流。     

人工肝干预肝衰竭凝血项变化的研究

急性肝衰竭是一种复杂的多系统疾病,短期内可迅速出现凝血功能障碍和肝性脑病等并发症,凝血功能障碍严重者可导致大量出血,是肝功能衰竭患者死亡的主要原因.目前急性肝衰竭的治疗主要包括内科综合治疗、人工肝支持系统、肝移植三种方法.本文就人工肝支持系统治疗对肝功能衰竭患者凝血项变化的影响做一综述.     

组合式生物人工肝治疗犬急性肝功能衰竭

目的 观察新型组合式生物人工肝治疗急性肝功能衰竭犬的作用.方法 D-氨基半乳糖给药构建犬急性肝功能衰竭模型,实验分组:组合式生物人工肝治疗组(n=8);生物人工肝治疗组(n=8);非生物人工肝治疗组(n=8);对照组(n=8).观察和检测所有犬一般情况、生化指标及生存率,同时进行安全性评价.结果 组合式生物人工肝具有良好的解毒及合成功能.4组犬的生存率分别是87.5％、62.5％、50.0％、37.5％,仅组合式生物人工肝组与对照组之间差异有统计学意义(P＜0.05),其余各组差异均无统计学意义(P＞0.05).结论 组合式生物人工肝对治疗急性肝功能衰竭具有良好的疗效.     

一种新型生物人工肝系统的构建及体外功能评价

目的　构建一种新型生物人工肝 (BAL )系统 ,并评价其体外功能。方法　采用原位胶原酶循环灌注法分离中国实验用小型猪肝细胞。 1× 10 1 0 肝细胞在无血清培养基中经限制贴壁、旋转培养形成肝细胞球体后 ,注入BIOLIVA3A中空纤维管生物反应器的细胞环路 ,构建新型BAL系统。观察循环 6h内细胞环路中肝细胞总数和活率变化 ,并检测循环的细胞悬液和RPMI164 0培养基中ALT ,TBI和ALB的变化及进行利多卡因代谢试验。结果　循环 6h内肝细胞总数和活率无明显变化 ;新型BAL系统具有较强的清 (白 )蛋白合成和利多卡因代谢能力。结论　该新型BAL系统具有一定的肝支持作用 ,可望用于肝衰竭的治疗和为过渡到肝移植创造条件     

Comparative study of bioartificial liver support and plasma exchange for treatment of pigs with fulminant hepatic failure

Recently, bioartificial liver (BAL) treatment was reported to provide beneficial effects for patients with fulminant hepatic failure (FHF). Some success in experimental or clinical trials has been reported; however, the evaluation of BAL efficacy remains unclear, especially in comparison with other treatments for FHF. The purpose of this study was to compare the efficacy between BAL and plasma exchange (PE) in experimentally induced FHF in pigs. Pigs undergoing hepatic devascularization (HD) were placed into the following groups: no treatment (control; n = 6), BAL treatment (BAL; n = 5), and plasma exchange (PE; n = 5). Each treatment was initiated 6 h after HD and lasted for 4 h. BAL treatment significantly improved liver functions in FHF pigs. The decrease in cerebral perfusion pressure was also significantly suppressed in the pigs with BAL, and their survival time was prolonged compared with the results in pigs with PE. The effects of BAL outperform those of PE in the treatment of experimental FHF model.     

Efficacy of an extracorporeal flat-plate bioartificial liver in treating fulminant hepatic failure

BACKGROUND: Fulminant hepatic failure is associated with a high mortality rate. Orthotopic liver transplantation is the only established treatment for patients who do not respond to medical management. A major limitation of this treatment is a shortage of donor organs, resulting in many patients dying while waiting for a transplant. An extracorporeal bioartificial liver (BAL) has the potential to provide temporary support for patients with fulminant hepatic failure (FHF) and for patients awaiting orthotopic liver transplantation. We developed a flat-plate BAL with an internal membrane oxygenator in which porcine hepatocytes were cultured as a monolayer. MATERIALS AND METHODS: Twenty-four hours after cannulation of the left carotid artery and right jugular vein, FHF was induced in rats by administering 2 intraperitoneal injections of D-galactosamine (GalN) (1.2 g/kg) at a 12-h interval. The rats were connected to a BAL device 24 h after the first GalN injection and underwent extracorporeal perfusion for a duration of 10 h. Liver histology, liver-specific markers, and animal survival up to 168 h (7 days) were examined. RESULTS: Histologically, liver damage was reduced in the animal group treated with the hepatocyte-based BAL device. Significant reductions occurred in the plasma ammonia levels and prothrombin times in the group treated with the seeded BAL device. Animal survival in the group treated with the seeded BAL device was significantly higher (50.0%) than in the control animal group treated with an unseeded BAL device (11.1%). CONCLUSIONS: This flat-plate BAL with an internal membrane oxygenator and cultured porcine hepatocytes has yielded encouraging results in the treatment of rats with GalN-induced FHF.     

Significant survival prolongation in pigs with fulminant hepatic failure treated with a novel microgravity-based bioartificial liver

The aim of this study was to evaluate the efficacy and safety of our novel Innsbruck Bioartificial Liver (IBAL; US patent no. 10/641275), which contains aggregates of porcine hepatocytes grown under simulated microgravity, in a porcine model of fulminant hepatic failure (FHF). FHF was induced by a combination of 75-80% liver resection and ischemia of the remnant segments for 60 min in 12 pigs. Two experimental groups were studied: the control group (n = 5) received standard intensive care and the study group (n = 5) received IBAL treatment. The survival of pigs with FHF was significantly prolonged by about 150% with IBAL treatment as compared to controls (controls: 20.4 +/- 2.8 h, IBAL: 51.0 +/- 2.2 h; P = 0.00184). In addition, intracranial pressure, blood ammonia, lactate, aspartate aminotransferase, and alkaline phosphatase levels were lower in the IBAL group than in controls, indicating metabolic activity of porcine hepatocytes in the bioreactor. No adverse effects were observed.     

肝移植治疗暴发性肝衰肝性脑病的临床研究

目的 总结肝移植治疗暴发性肝衰肝性脑病的临床经验。方法 回顾性分析４例暴发性肝衰肝性病病人行肝移植手术治疗的临床资料。结果 肝移植治疗暴发性肝衰肝性脑病１个月存活率７５％（３／４）,超过３个月存活率为５０％（２／４）。结论 肝移植是治疗暴发性肝衰肝性脑病的一种有效方法,暴发性肝衰肝性脑病不是肝移植手术的禁忌证。     

闭合型双循环生物人工肝支持系统治疗犬急性肝功能衰竭实验研究

目的探讨和评价闭合型双循环生物人工肝支持系统(CBC-BALSS)在治疗犬急性肝功能衰竭模型过程中的稳定性、安全性和有效性。方法建立犬急性肝功能衰竭模型(门腔分流联合胆总管离断),采用CBC-BALSS进行支持治疗。20只模型犬分为两组CBC-BALSS治疗组(n=11);无肝细胞CBC-BALSS对照组(n=9)。治疗时限6h。检测实验犬血氨、生化全套、凝血因子(FactorⅦ)、支/芳氨基酸(BCAA/AAA)、单乙基甘氨酸二甲苯胺(monoethylglycinexylidide,MEGX)和细胞循环路生化全套、肝细胞密度和数量。结果CBC-BALSS细胞回路细胞悬液总体积200ml,肝细胞的总数1×1010个、密度5×107/ml、活率98%左右。治疗中16只犬的生命体征平稳,在治疗30min内均出现一过性低血压;2只转流开始15min出现过敏反应;1只转流中因上消化道出血死亡;1只因穿刺部位出血死亡。模型治疗前血氨、ALT、TBil/DBil、白蛋白、FactorⅦ和BCAA/AAA分别达150mmol/L、400U/L、80/55mmol/L、35g/L、20%和1.6;CBC-BALSS治疗6h后,血氨、TBil/DBil下降均显著低于对照组;ALT存在下降趋势且在第6小时差异有统计学意义;白蛋白、FactorⅦ和BCAA/AAA在所有时段、组间差异均无统计学意义。在治疗1h和2h,MEGX差异有统计学意义,治疗组MEGX比对照组提前2h达最高点。治疗15~30min后,双循环路压力至115mmHg趋于平稳,且在±5mmHg波动。在治疗过程中,治疗组细胞循环路ALT显著性升高;组间细胞循环路TBil/DBil变化差异无统计学意义,而两组在各时间点均显著性升高;白蛋白变化无统计学意义。结论CBC-BALSS治疗犬急性肝功能衰竭过程中,安全、有效、稳定且代谢支持作用明显。     

Liver transplantation for fulminant hepatic failure: importance of renal failure

Abstract One hundred eighty-one consecutive patients with fulminant hepatic failure (FHF) presenting in a 2-year period were reviewed. In this cohort we examined the impact of pretransplant renal failure on mortality and morbidity following orthotopic liver transplantation (OLTx). Twenty-seven patients (18 female, 9 male) with a median age of 43.5 years (range 19–65 years) underwent OLTx. FHF was due to idiosyncratic drug reaction ( n = 4), paracetamol overdose ( n = 3), seronegative hepatitis ( n = 17), hepatitis B ( n = 1), veno-occlusive disease ( n = 1), and Wilson's disease ( n = 1). Renal failure was present in 14 patients, 7 of whom died (whereas there was 100 % survival in patients without renal failure). Pretransplant renal failure was associated with prolonged mechanical ventilation (13 days vs 6 days, P = 0.05), prolonged intensive care stay (17 days vs 8 days, P - 0.01) and prolonged hospital stay (27 vs 21 days, P = NS). Pretransplant renal failure did not predict renal dysfunction at 1 year after OLTx. We conclude that the survival of patients transplanted for FHF is inferior to that of patients transplanted for chronic liver disease (67 % vs 88 % 1-year survival in Birmingham). For patients with FHF undergoing transplantation, pretransplant renal failure strongly predicts poor outcome with significantly greater consumption of resources.     

Liver transplantation for fulminant hepatic failure: Importance of renal failure

One hundred eighty-one consecutive patients with fulminant hepatic failure (FHF) presenting in a 2-year period were reviewed. In this cohort we examined the impact of pretransplant renal failure on mortality and morbidity following orthotopic liver transplantation (OLTx). Twenty-seven patients (18 female, 9 male) with a median age of 43.5 years (range 19–65 years) underwent OLTx. FHF was due to idiosyncratic drug reaction (n = 4), paracetamol overdose (n = 3), seronegative hepatitis (n = 17), hepatitis B (n = 1), veno-occlusive disease (n = 1), and Wilson's disease (n = 1). Renal failure was present in 14 patients, 7 of whom died (whereas there was 100% survival in patients without renal failure). Pretransplant renal failure was associated with prolonged mechanical ventilation (13 days vs 6 days,P = 0.05), prolonged intensive care stay (17 days vs 8 days,P = 0.01) and prolonged hospital stay (27 vs 21 days,P = NS). Pretransplant renal failure did not predict renal dysfunction at 1 year after OLTx. We conclude that the survival of patients transplanted for FHF is inferior to that of patients transplanted for chronic liver disease (67% vs 88% 1-year survival in Birmingham). For patients with FHF undergoing transplantation, pretransplant renal failure strongly predicts poor outcome with significantly greater consumption of resources.     

Liver transplantation for fulminant liver failure in children

The mortality rate of fulminant hepatic failure (FHF) in childhood has remained between 70% and 95% despite recent improvements in medical therapy. Liver transplantation has become an important therapeutic option in adults with this entity, but has been infrequently performed in children. Many children do not receive transplants because of the rapid progression of the illness and the lack of suitable donor livers. We present our experience in liver transplantation in children with FHF. Between March 1988 and December 1989, seven children aged between 15 months and 12 years received eight liver transplants. The aetiology of FHF was viral hepatitis in five and drug hepatotoxicity (carbamazepine) in two. Five of our patients were in grade III—IV coma. Reduced-sized livers were used in six of the eight transplants. The post-operative morbidity included viral and fungal infections, and abdominal bleeding. Two patients died from graft-versus-host disease and one from brain aspergillosis. Four patients (57%) survived a median follow-up of 15 months. Liver transplantation should be the therapeutic option in children with FHF where the chances of medical recovery are poor.