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 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.     

肝移植治疗暴发性肝功能衰竭

fulminant liver failure(FLF)is a rapid onset life-threatening emerency in which liver dysfunction,liver failure and hepatic encephalopathy occur within 8 weeks in previouslv norillal person.It has been confirmed by available clinical experience and literatures during the past decades that FLF patients are ideal recipients of liver transplantation.However,the prognosis of the FLF patients who accepted liver transplantation differed greatly according to the available reports because of the differences of supportive treatment during waiting period,the criterion for recipient assessment,the determination of operation chance,the use of critical techniques during operation and postoperative management between different transplantation centers.We probe the standardized clinical use of the aspects above mentioned in liver transplantation for FLF,particularly discuss the treatment of complications resulting from coagulopathy,determination of operation chance,significance of standardized etiological treatment and the indication of the use of veno-venous bypass technique during transplantation to provide better treatment strategy and improve the prognosis of FLF patients.     

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。     

Liver transplantation for the treatment of fulminant hepatic failure induced by the ingestion of ecstasy

Methylenedimethoxymethamphetamine (MDMA), more commonly known as ecstasy, is a synthetic amphetamine derivative used by teenagers and young adults in the United States as well as in Western Europe as a “dance drug“. Though a number of complica Received: 2 July 1996 Received after revision: 6 December 1996 Accepted: 16 December 1996     

肝移植治疗暴发性肝功能衰竭17例临床观察

目的 观察肝移植治疗暴发性肝功能衰竭的效果及失败原因。方法 总结本所17例暴发性肝衰行肝移植治疗的临床资料。结果 17例暴发性肝衰行肝移植6例存活1年，1年存活率为35．3％。死亡原因分别为肺部感染致呼吸衰竭6例，多器官衰竭2例，术后胸腔大出血1例，DIC1例，颅内出血1例。结论 病人术前状况决定肝移植效果；肺部并发症是暴发性肝功能衰竭肝移植术后死亡的主要原因。     

Isoniazid-related fulminant hepatic failure in a child: assessment of the native liver's early regeneration after auxiliary partial orthotopic liver transplantation

Abstract We report the first case of auxiliary partial orthotopic liver transplantation (APOLT) in a patient with isoniazid (INH)-related fulminant hepatic failure (FHF) with the aim to determine the ability of the native liver (NL) to recover after this particular toxic event. A 10-year-old boy with INH-related FHF underwent APOLT after left hepatectomy on the NL. Neurological status and liver function rapidly improved, but, on postoperative day 22, urgent re-transplantation was needed for graft-hepatic artery thrombosis (HAT) and the NL's incapacity to sustain adequate liver function. Histological examination of the NL showed signs evident of its regeneration, however. In conclusion, though we faced the clinical failure of the NL functionally to sustain the patient in the presence of the graft HAT 3, weeks after APOLT, such a failure may be interpreted as time related. In fact, the histological picture in this particular case may suggest the potential for NL recovery after INH-related FHF     

Fulminant hepatic failure post liver transplantation: clinical syndromes,correlations and outcomes

This paper reports the clinical syndrome of fulminant hepatic failure (FHF) following liver transplantation. FHF was defined as the sudden onset of liver failure [encephalopathy and prolonged International Normalised Ratio (INR)] without arterial thrombosis in the setting of a liver allograft. FHf post-transplant was seen in 8/154 (5.2%) adult patients undergoing transplantation. These eight patients developed a clinical syndrome characterised by: (a) a rapid rise in ALT levels to above 1000 U/l (mean maximum 1600 U/l), (b) a sudden increase in the INR to above 5 (mean maximum 5.6), (c) the development of high fever, (d) the persistence of thrombocytopenia (mean nadir 40×10⁹/dl), (e) a progressive rise in the bilirubin (mean maximum 400 mol/l) and (f) the development of hepatic encephalopathy. In seven cases this syndrome occurred following good initial graft function at day 6 post (mean)-transplant. In one case the above syndrome developed immediately after liver transplantation. Four of the eight patients developed multiorgan failure associated with systemic acidosis (mean pH 6.84). All of these patients died (mean day 11). Four patients developed systemic alkalosis. Two of these four patients underwent successful retransplantation (on days 12 and 13) and remain alive at a mean of 11 months post-transplant. Six of the eight patients received OKT3 therapy without any apparent affect on clinical outcome. Compared to a control group of patients (n=28), 2/8 versus 2/28 had a positive crossmatch with donor lymphocytes (P=NS), 1/8 versus 7/28 were ABO-non-identical (P=NS), 3/8 versus 10/21 had total MHC mismatches (P=NS) and 5/7 versus 6/16 had UW ischemic times above 10 h (P=NS). No patients had main hepatic artery thrombosis on angiography although four patients had evidence of intrahepatic microthrombi or arterial necrosis at autopsy. In all cases the histology showed massive haemorrhagic necrosis. Three cases had evidence of veno-occlusive lesions whilst foam cell arteriopathy was seen in two cases. Immunofluorescence was performed in three cases. In two cases there was evidence of immunoglobulin, complement and fibrin deposition in blood vessels. In conclusion, we describe an uncommon clinical syndrome occurring post liver transplant. This syndrome represents humorally mediated allograft rejection but there seems to be no relationship with tissue matching (antibody, ABO, MHC) or donor ischaemic times. If recognised earlier in the absence of multiorgan failure, urgent retransplantation seems to be the only effective therapy.     

肝移植术后早期急性肾功能衰竭5例临床分析

目的总结肝移植术后早期急性肾功能衰竭的防治经验。方法回顾性分析5例肝移植受者术后早期发生急性肾功能衰竭临床资料,手术方式为改良背驮式肝移植术,其中4例术前即合并肾功能不全。结果5例术后早期急性肾功能衰竭患者3例通过调整免疫抑制方案和改善肾脏灌注及利尿治疗肾功能恢复;2例给予连续性肾脏替代治疗后肾功能恢复。结论肝移植术后免疫抑制剂的个体化应用,积极改善肾脏灌注,必要时选择血液透析治疗,有助于防治肝移植术后早期急性肾功能衰竭。     

The importance of orthotopic liver transplantation in acute hepatic failure

Selection of patients with acute hepatic failure for liver transplantation remains difficult, and there is no definite proof of a survival effect. We therefore did a retrospective study in 75 consecutive patients referred over a 12-year period. In two-thirds we identified a cause, mostly viruses or drugs. Patients were grouped by the Clichy and King's College criteria. In 20 there was no indication for transplantation. Of the 5 with autoimmune hepatitis, 3 died, significantly differing from the other 15 ( P = 0.009). The remaining 55 met our criteria, except 1. All 9 patients with absolute contraindications died. Of the 46 enlisted, 7 died without transplantation. One-year survival after transplantation was 69%, compared with 58% by "intention to treat." For patients enlisted, transplantation reduced mortality by 78% ( P = 0.069). The Clichy and King's College criteria reliably predict survival without transplantation, except in autoimmune hepatitis. Our study strongly suggests that transplantation improves survival.     

Compressed spectral arrays of patients with fulminant hepatic failure in hepatic coma undergoing liver transplantation

Assessing the coma status of patients with fulminant hepatic failure (FHF) is important for determining the reversibility of brain damage and for properly timing liver transplantation. The compressed spectral array (CSA) method is a frequency analysis technique that processes electroencephalogram signals by computer to facilitate on-line interpretation. This method has been used to monitor the consciousness levels of neurointensive care unit patients. In this study, we determined whether CSA could be used to assess the coma status of patients with FHF, and whether CSA provided information that was useful in deciding when to proceed with liver transplantation. CSA recording was carried out in 17 FHF patients with encephalopathy (coma grade III-IV) who underwent living-related liver transplantation between August 1997 and May 1999. Recording was performed with a Neuromonitor OEE-72044 (NIHON KOHDEN, Osaka, Japan) every 24 h before and after transplantation, until the patients regained consciousness. The CSAs of healthy controls were distributed almost equally between 0 and 16 Hz. The CSAs of FHF patients in hepatic coma were classified into three patterns. Eight of the 17 patients showed very prominent slow waves of about 2 Hz (group A), and seven patients showed strongly suppressed rapid waves between 8 and 16 Hz (group B). The remaining two patients showed CSA patterns that were similar to those of healthy controls, even though these patients were comatose (group C). Abnormal CSA patterns were observed in 15 of the 17 patients (88%). Group B patients seemed to have higher coma grades than did group A patients. Sixteen patients underwent liver transplantation, completely recovered from hepatic encephalopathy, and subsequently showed CSA patterns similar to those of healthy controls. One patient died without regaining consciousness. These results suggest that CSA is useful in assessing the coma status of FHF patients and in evaluating electrophysiological recovery from hepatic coma after liver transplantation.     

体外生物人工肝系统对暴发性肝衰竭兔的支持作用

目的探讨培养肝细胞用于生物人工肝及其作为肝移植辅助支持手段的可能性。方法以培养人肝细胞和中空纤维反应器为主要材料构成体外生物人工肝系统,对Ｄ-氨基半乳糖诱导的暴发性肝衰竭（ＦＨＦ）免进行人工肝支持实验。结果尽管两组实验动物的存活时间没有明显差异,但支持治疗组兔的血清转氨酶、总胆红素和肌酐水平均低于对照组,肝组织病理检查见肝细胞坏死程度明显轻于对照组,实验所用肝细胞保持较好的活力和贴壁能力。结论所用体外生物人工肝支持系统已发挥出培养肝细胞的生物作用,能够部分代偿ＦＨＦ兔的肝脏功能。【关键词】##4人工肝;;支持;;暴发性肝衰竭;;兔     

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。     

肝移植相关性肾功能衰竭的防治

目的 总结肝移植相关性肾功能衰竭(肾衰)的防治经验。方法 回顾性分析36例术后早期肝移植相关性肾衰防治方法的改进及效果。结果 36例肝移植受者中，死亡10例，死亡率为27．78％。术后并发症：肺部感染22例；多器官功能衰竭11例；成人呼吸窘迫综合征(ARDS)14例；腹腔内出血4例；胆漏1例。术后2例存活超过3年，4例存活超过2年，9例存活超过1年。结论 采用背驮式肝移植；改进连续性肾替代治疗(CRRT)的使用方法；术后早期使用赛尼哌；减少或完全不用钙调素抑制剂；是提高肝移植相关性肾衰治疗成功率的关键。     

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.     

Continuous peritransplant assessment of consciousness using bispectral index monitoring for patients with fulminant hepatic failure undergoing urgent liver transplantation

Hwang S, Lee SG, Park JI, Song GW, Ryu JH, Jung DH, Hwang GS, Jeong SM, Song JG, Hong SK, Lim YS, Kim KM. Continuous peritransplant assessment of consciousness using bispectral index monitoring for patients with fulminant hepatic failure undergoing urgent liver transplantation.
Clin Transplant 2010: 24: 91–97. © 2009 John Wiley & Sons A/S. Abstract: Background: Rapid deterioration of consciousness is a critical situation for patients with fulminant hepatic failure (FHF). Bispectral (BIS) index was derived from electroencephalography parameters, primarily to monitor the depth of unconsciousness. Aim: To assess the usability of peritransplant BIS monitoring in patients with FHF. Methods: A prospective study using peritransplant BIS monitoring was performed in 26 patients with FHF undergoing urgent liver transplantation (LT). Results: Pre‐transplant Child‐Pugh score was 12.2 ± 1.0; model for end‐stage liver disease score was 32.4 ± 4.4; Glasgow coma score (GCS) was 9.9 ± 1.3; and BIS index was 44.0 ± 6.7. Pre‐transplant sedation significantly decreased BIS index. After LT, all patients having endotracheal intubation recovered consciousness within one to three d and showed progressive increase in BIS index, which appeared slightly earlier and was more evident than the increase in derived GCS score. There was a significant correlation between BIS index and derived GCS scores (r² = 0.648). Timing of eye opening to voice was matched with BIS index of 66.3 ± 10.4 and occurred 12.7 ± 8.3 h after passing BIS index of 50. Conclusion: These results suggest that BIS monitoring is a non‐invasive, simple, easy‐to‐interpret method, which is useful in assessing peritransplant state of consciousness. BIS monitoring may therefore be a useful tool during peritransplant intensive care for patients with FHF showing hepatic encephalopathy.     

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.     

肝移植术后早期急性肾功能衰竭处理及危险因素分析

目的探讨肝移植术后早期急性肾功能衰竭的处理及相关危险因素。方法回顾分析400例肝移植临床资料，观察术后急性肾功能衰竭病人的处理及预后。根据有无肾功能衰竭分组，对13项相关的危险因素进行单因素及多因素分析。结果肝移植术后早期急性肾功能衰竭的发生率为7．2％，均接受持续静脉静脉血液滤过治疗，1年生存率为44．4％。单因素分析中年龄、术前肝功能分级、术前肌酐、尿素氮、手术时间、术中输血量组间差异有统计学意义，多因素分析中只有术前肝功能分级是独立的危险因素。结论肝移植术后早期急性肾功能衰竭预后差，可能与多种诱发因素有关，术前肝功能不全是独立的危险因素。