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.     

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。     

小体积肝移植和辅助性原位小体积肝移植治疗猪急性肝功能衰竭的近期疗效观察

目的观察小体积肝移植和辅助性原位小体积肝移植治疗猪急性肝功能衰竭的近期疗效。方法急性肝功能衰竭猪随机分为3组接受肝移植治疗:A组行全肝移植(n=5);B组行小体积肝移植(n=5);C组行辅助性原位小体积肝移植(n=5)。各组动物开腹后即刻、切脾后即刻和再灌注后30 min分别监测门静脉压力,并观察术后生化指标变化、病理改变和1周生存率。结果A、B和C三组的移植肝重量与受体体重之比分别为(2．44±0．30)％、(0．76±0．02)％和(0．75±0．03)％。再灌注后30 min,B组移植肝门静脉压力显著高于其它两组(A:B:C=13．3:17．5:12．2 cmH2O, P<0．01),C组原肝门静脉压力显著高于移植肝门静脉压力(14．3:12．2 cmH2O,P<0．05)。A组和C组术后第2天起血清天冬氨酸转氨酶、总胆红素、凝血酶原时间、乳酸和血氨水平明显下降,术后第7天基本恢复至正常水平。B组术后上述生化指标一直维持在较高的水平,术后第2～4天明显高于其它两组(P<0．01)。A组、B组和C组1周生存率分别为100％、20％和80％,B组明显低于其它两组(P<0．05)。结论辅助性原位小体积肝移植治疗急性肝功能衰竭近期疗效优于小体积肝移植,术中不必干预原肝门静脉。     

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。     

Incorporating dynamics for predicting poor outcome in acute liver failure patients

Acute liver failure (ALF), also known as fulminant hepatic failure (FHF), is a devastating clinical syndrome with a high mortality of 60%-90%. An early and exact assessment of the severity of ALF together with prediction of its further development is critical in order to determine the further management of the patient. A number of prognostic models have been used for outcome prediction in ALF patients but they are mostly based on the variables measured at one time point, mostly at admission. ALF patients rarely show a static state: rapid progress to a life threatening situation occurs in many patients. Since ALF is a dynamic process, admission values of prognostic variables change over time during the clinical course of the patient. Kumar et al developed a prognostic model [ALF early dynamic (ALFED)] based on early changes in values of variables which predicted outcome. ALFED is a model which seems to be worthwhile to test in ALF patients in other parts of the world with different aetiologies. Since the exact pathophysiology of ALF is not fully known and is certainly complex, we believe that adding promising variables involved in the pathophysiology of ALF to the dynamic approach might even further improve prognostic performance. We agree with Kumar et al that an improved dynamic prognostic model should be based on simplicity (easily to be performed at the bedside) and accuracy. Our comments presented in this paper may be considered as recommendations for future optimization of ALF prediction models.     

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.     

Insulin-like growth factor-I increases p21 expression and attenuates cisplatin-induced acute renal injury in rats

Background Exogenous insulin-like growth factor-I (IGF-I) promotes recovery from ischemic renal injury, but its effect on cisplatin (CDDP)-induced nephrotoxicity and its mechanisms for the attenuation of renal injury are unknown.Methods We administered recombinant human IGF-I (rhIGF-I, 150µg/day, i.p.) once a day 24h prior to and after CDDP (5mg/kg, i.v.) injection in rats.Results The rhIGF-I treatment significantly decreased serum creatinine (0.92 ± 0.11 vs 1.50 ± 0.15mg/dl; P 0.05), the tubular damage score, and the ratio of apoptotic cells to tubular epithelial cells in the outer stripe of the outer medulla on day 5 (P 0.05). rhIGF-I significantly increased the numbers of p21-positive nuclei (5.15 ± 0.19 vs 3.45 ± 0.42/×400 high-power field (HPF); P 0.05) and proliferating cell nuclear antigen (PCNA)-positive nuclei (28.61 ± 1.89 vs 18.26 ± 2.14/×400 HPF; P 0.05), but decreased the number of cyclin D1-positive cells (3.3 ± 0.3 vs 6.3 ± 1.7/×400 HPF; P 0.05) on day 3. rhIGF-I did not alter 5-bromo-3-deoxyuridine (BrdU) incorporation.Conclusions Our findings suggested that rhIGF-I increased renal p21 and PCNA expression, but reduced cyclin D1 expression in CDDP-treated kidneys. Exogenous rhIGF-I may ameliorate renal damage, in part by stopping the cell cycle at G1/S phase.     

Bioartificial liver treatment prolongs survival and lowers intracranial pressure in pigs with fulminant hepatic failure

Intracranial hypertension leading to brainstem coning is a major cause of death in fulminant hepatic failure (FHF). We have developed a bioartificial liver (BAL) utilizing plasma perfusion through a bioreactor loaded with porcine hepatocytes and a column with activated charcoal. In a Phase I clinical trial, we observed a decrease in intracranial pressure (ICP) in FHF patients. However, these patients received BAL therapy together with other measures. We therefore examined whether BAL therapy alone could prevent development of intracranial hypertension in pigs with surgically induced FHF. Pigs (40-60 kg) underwent end-to-side portacaval shunt, transection of all hepatic ligaments, and placement of slings around the hepatic artery and bile duct. After 3 days, the slings were tightened to induce liver necrosis. After 4 h, Group 1 pigs (n = 6) underwent a 6 h treatment with the BAL utilizing 10 billion cryopreserved pig hepatocytes and a charcoal column, Group 2 pigs (n = 6) with the BAL containing charcoal but no cells, and Group 3 pigs (n = 6) with the BAL containing neither cells nor charcoal. Group 1 pigs maintained a normal ICP during BAL treatment and for 14 h afterward and because of this effect they survived longer than Groups 2 and 3 animals. In contrast, Groups 2 and 3 pigs showed an early (6-8 h) rise in ICP.     

Abdominal imaging can misdiagnose submassive hepatic necrosis as cirrhosis in acute liver failure

Patients with acute liver failure (ALF) can be listed status I for liver transplantation (LT) whereas patients with cirrhosis must follow the MELD scoring system. Liver imaging can mistakenly diagnose submassive hepatic necrosis in ALF as cirrhosis. The purpose of our study was to assess the accuracy of ultrasound (US) and computed tomography (CT) in distinguishing cirrhosis from ALF. All patients listed for ALF and transplanted during the study period were included. Controls were age‐ and gender‐matched cirrhotic patients who underwent LT during the same period. Abdominal US or CT scans obtained on all patients were independently reviewed by three blinded abdominal radiologists. Explants from all patients were reviewed by two blinded pathologists, and histological diagnosis was correlated with radiological diagnosis. Forty‐one patients with ALF and 42 patients with cirrhosis were analyzed. Univariate and multivariate analyses both revealed overall accuracy of 85% for ultrasound and 93% for CT. US and CT scans both provide high levels of accuracy in terms of discriminating ALF from cirrhosis but measures taken to determine whether a patient has ALF vs. cirrhosis needs to approach 100% accuracy. Thus, imaging studies alone should not definitively diagnosis one etiology of liver failure over the other.     

大鼠原位辅助性肝移植治疗急性肝功能衰竭

为了评价大鼠原位辅助性部分肝移植（ＡＰＯＬＴ）对急性肝功能衰竭的支持作用。切除７５％的肝脏并阻残余肝脏的血供５０分钟导大鼠急性肝功能衰竭。治疗组受体计切除７５％并将３０％的供肝植于原位，然后阻断残余的右上叶的右下叶之血供５０分钟。结果显示，大鼠急性肝功能衰竭的５天生存率仅３３％，而接受ＡＰＯＬＴ者５天生存率和移植肝存活率分别为８０％和７３％，术后第５天肝功能基本恢复正常。可见，大肝切除和余肝缺血诱     

骨桥蛋白和p21蛋白在直肠癌组织中的表达及意义

目的 检测骨桥蛋白(OPN)和p21蛋白在直肠癌组织中的表达及其临床意义,并探讨两种蛋白之间的相关性.方法 采用免疫组织化学染色法检测51例直肠癌手术标本和30例正常直肠组织中OPN和p21蛋白的表达情况.结果 ①OPN和p21蛋白在直肠癌组织中的阳性表达率分别为54.9%(28/51)和62.75%(32/51),在正常直肠组织中均未见有阳性表达.两蛋白在直肠癌和正常直肠组织中的阳性率差异有统计学意义(P<0.01).②OPN高表达与浸润深度、分化程度、淋巴结转移有关(P<0.05),与直肠癌患者的性别、年龄、肿瘤大小无关(P＞0.05);p21蛋白高表达与淋巴结转移显著相关(P<0.01),而与直肠癌患者性别、年龄、肿瘤大小、浸润深度、分化程度无关(P＞0.05).③OPN、p21蛋白均阳性表达的24例直肠癌中全部发生淋巴结转移,与两者均阴性表达的15例直肠癌中仅有2例(13.3%)发生转移相比较,差异有统计学意义(P<0.01).④OPN和p21蛋白在直肠癌中的表达呈正相关(r＝0.524,P<0.01).结论 OPN和p21蛋白高表达可能参与了直肠癌的发病,联合检测两者蛋白表达对评估直肠癌预后具有重要意义.     

Toll样受体4单克隆抗体对慢加急性肝功能衰竭大鼠的保护作用

目的：观察Toll样受体4（TLR4）单克隆抗体对慢加急性肝功能衰竭大鼠的治疗效果以及对高迁移率族蛋白B1（HMGB1）的影响。方法采用人血白蛋白,D-氨基半乳糖以及LPS联合诱导的大鼠慢加急性肝功能衰竭模型,并应用TLR4单克隆抗体作为干预剂以及兔抗鼠IgG作为对照,观察TLR4单克隆抗体对慢加急性肝功能衰竭大鼠的肝脏组织学、血清ALT、TNF-α、IFN-γ、HMGB1水平以及肝组织中HMGB1水平的影响。结果 TLR4单克隆抗体能够明显改善慢加急性肝功能衰竭大鼠肝脏组织病理学损害,降低血清中ALT、TNF-α、IFN-γ和HMGB1水平,并且降低肝组织中HMGB1水平（P均＜0.05）。而与模型组相比,以上指标在对照组中差异无统计学意义（P均＞0.05）。结论 TLR4单克隆抗体能够保护慢加急性肝功能衰竭大鼠并减少HMGB1胞外释放以及肝组织中HMGB1的产生。     

猪原位辅助性部分肝移植治疗急性肝功能衰竭的模型

目的建立猪原位辅助性肝移植(APOLT)治疗急性肝功能衰竭的动物模型,并评价其治疗效果。方法选取健康雌性良种幼猪18头,其中12头建立急性肝功能衰竭模型,另6头作为肝移植的供者。将急性肝功能衰竭的幼猪随机平均分为2组:对照组,不作任何处理;实验组,进行APOLT术,切除受者肝脏左叶,将修整后的供肝右叶移植于原肝左叶肝床处,供肝肝上下腔静脉与受者肝肝上下腔静脉行端侧吻合,供肝门静脉与受者肝门静脉行端侧吻合,受者脾动脉在结肠后与供肝动脉行端端吻合,胆总管置管外引流。结果对照组7d生存率仅为17%,而实验组为83%。实验组术后第7d肝功能基本恢复正常,组织学检查示原肝细胞再生明显。结论门静脉注射氨基半乳糖 脂多糖诱导的猪急性肝功能衰竭是一个理想的动物模型;APOLT对急性肝功能衰竭具有较好的疗效。     

肝移植治疗药物性急性肝衰竭的体会（附8例报告）

目的 探讨肝移植治疗药物性急性肝衰竭的疗效.方法 药物性急性肝衰竭患者8例,术前肝功能Child-Pugh分级均为C级,均合并肝性脑病（Ⅲ～Ⅳ期）.所有患者均行经典原位肝移植,供体均为尸体供肝,均未行静脉转流.术后予免疫诱导、免疫抑制治疗,并予抗感染及支持治疗.结果 8例患者均顺利完成肝移植手术.术后1例女性患者并发原发性移植肝无功能,死亡.余7例患者于术后16～72 h苏醒.1例发生胆道铸型结石,手术取石效果不佳,予再次肝移植,行胆总管空肠吻合术,术后发生吻合口漏死亡.其余6例存活患者均痊愈,生活状况良好.其中2例曾发生急性呼吸窘迫综合征,行气管切开、呼吸机辅助呼吸,最后康复出院.结论 对于保守治疗无效的药物性急性肝衰竭,肝移植是唯一有效的治疗措施.     

原发性肝癌切除术后发生肝功能代偿不全的临床研究

目的: 探讨了解肝部分切除术后出现肝功能不全的可能原因. 方法: 将63例原发性肝癌患者分成3组,比较分析各组的手术后生存时间与生存率、术后复发率、术前、术后的主要肝功能指标,术后一年内出现肝功能不全的原因与频率,以及死亡患者的死亡原因与时间等. 结果: 平均随访时间为(25±21.3)个月,各组生存率无显著性差异,总复发率为56%(35/63),平均复发时间为17个月;术后死于复发癌的时间为(22±12.3)个月,死于肝功能不全的时间为(4.8±3.7)个月,术前肝功能储备差者,术后易发生代偿不全,术后早期死亡者大多由肝功能不全所致. 结论: 对原发性肝癌病人行肝部分切除术时,要充分了解肝功能储备,术后早期积极给予保肝治疗.     

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.