A rat model of monitoring liver allograft rejection

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 ± 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 ± 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 ± 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1 % ± 2 % to 21 % ± 13 %) and class II (from 20 % ± 9 % to 43 % ± 13 %) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection. Received: 2 July 1996 Accepted: 28 October 1996     

Clinical pharmacokinetics of Neoral in pediatric recipients of primary liver transplants

Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests taken during i. v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively, and the bioavailabilities were 22 % and 21 % for the first and last NEO doses. A large interpatient variability was observed. This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability. Received: 29 November 1996 Received after revision: 10 April 1997 Accepted: 15 May 1997     

Successful regrafting of a transplanted liver

We report on the successful regrafting of a transplanted liver. The donor liver was first grafted into a patient suffering from cryptogenic cirrhosis; the patient died 1 day after the elective transplantation of cerebral bleeding. The well-functioning graft was harvested again and transferred to our institution. After another 12 h of cold ischemia, the liver was reperfused in an urgently registered patient with recurrence of hepatitis B in his first graft. The transplantation was successfully performed and the patient is now doing well, more than 5 months after regrafting with the reused liver. Received: 21 October 1996 Received after revision: 9 January 1997 Accepted: 27 January 1997     

Percutaneous technique for venovenous bypass including a heat exchanger is safe and reliable in liver transplantation

We have introduced and evaluated several modifications of the conventional venovenous bypass (VVBP) in 29 adult patients undergoing liver transplantation (OLT). A percutaneous technique for insertion of a jugular venous return cannula and a femoral vein cannula was applied. The inferior mesenteric vein (IMV) was used for splanchnic decompression, which facilitated dissection of the recipient liver and allowed portal anastomosis to be performed without disconnecting the portal bypass. A heat exchanger was introduced into the bypass circuit to prevent heat loss. The percutaneous technique prevented complications related to dissection in the axilla and groin. Hemodynamic characteristics corresponded to those found using the traditional technique. Complications related to the VVBP were seen in only one patient in whom the femoral catheter was accidentally introduced into the femoral artery. We conclude that percutaneous cannulas, use of the IMV for splanchnic decompression and the introduction of a heat exchanger offer significant benefits and that they are safe and reliable. Received: 23 August 1996 Received after revision: 14 January 1997 Accepted: 27 January 1997     

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.     

Variations in peroxisomal catalase of neonatal rat hepatocyte subpopulations

Alcohol consumption during pregnancy is teratogenic and induces severe alterations in hepatocytes. In the hepatocyte peroxisomal system, ethanol is converted in the presence of H₂O₂ to acetaldehyde and water. Therefore, peroxisomal catalase also acts as an antioxidant defence mechanism by removing H₂O₂ and preventing the formation of hydroxyl radicals in the cell. Alterations in peroxisomal catalase after pre- and pre+postnatal alcohol exposure were investigated in the rat. The effect of pre- and postnatal exposure to ethanol on hepatocyte subpopulations was analysed in isolated hepatocytes originating from periportal, intermediate and perivenous zones. Analysis of catalase revealed that the total activity and content of this enzyme were higher in 12-day-old cells than in cells from newborns and that this increment was more pronounced in treated cells. In controls, the amount of peroxisomal catalase increased mainly in periportal cells, whereas alcohol exposure induced a significant increase in the catalase of perivenous hepatocytes. We conclude that pre- and postnatal alcohol exposure mainly affects the perivenous hepatocyte peroxisomes and that the increase in peroxisomal catalase could constitute a defence mechanism against free radical generation induced by alcohol exposure during the perinatal period.     

用不灌洗法保存犬肝的电镜观察

本实验证明,用不灌洗法在25℃、15℃保存犬肝的有效时限分别是3小时和4小时,用Sacks液低温灌洗在4℃保存犬肝的有效时限至少是6小时。这表明用不灌洗法进行立即肝移植是可行的。     

原发性肝癌,肝硬化患者血清中丙肝病毒抗体的检测

应用国产ELISA试剂盒对157例肝癌、肝硬化病人血清中抗-HCV及HBV-M进行检测，101例肝癌10例抗-HCV阳性，阳性率为9．9％；56例肝硬化6例抗-HCV阳性，阳性率为10．7％；肝癌组抗HCV与HBsAg双阳性率79％（8／101），HBsAg阳性率为723％（73／101），明显高于HCV感染率，说明HBV仍是乙肝流行地区的主要相关因素。14例抗-HCV阳性（包括可疑阳性），肝癌外周血中8例（57．1％）HBsAg阳性，推测HCV可单独作用但更常与HBV形成混合感染参与慢性肝病的癌变过程。     

肝VX-2 瘤模型MR扩散成像的实验研究

目的探讨肝VX-2瘤模型MR扩散成像特征.方法新西兰大白兔35只,采用块种植的方法,一期预实验皮下种植14只,肝内种植6只;二期肝内种植12只,另3只做正常对照.对包括二期肝内种植在内的15个肿瘤于种植前后行定期扩散加权成像(DWI) 与MR检查.以表观扩散系数(ADC)值等为指标进行统计分析.结果 (1)一期预实验,皮下种植成功率29%(4/14),肝内种植成功率33%(2/6);二期肝内种植成功率83%(10/12).(2)VX-2瘤在DWI上呈高信号,边缘清楚.正常组与VX-2瘤实验组b值为100和300 s/mm2时ADC值分别为(2.57±0.26)mm2/s、(1.73±0.31)mm2/s、(1.87±0.25)mm2/s与(1.57±0.23)mm2/s(F=43.26,P<0.001).随b值增大,病灶信号降低;ADC图上病灶呈低信号;不同b值之间病灶ADC值差异有统计学意义(P<0.05);b=100 s/mm2病灶与正常肝脏之间ADC值差异有统计学意义(P<0.01).(3)VX-2瘤发展迅速,易发生肺、肝、纵隔等处转移.结论 DWI在反映肝VX-2瘤内部水分子运动、发现与追踪病灶进展等方面有重要价值.     

肝移植手术中的配合

自从 1 96 3年Starzl成功实施世界上第一例活体肝移植后 ,肝移植手术已经成为现代肝脏外科学领域里的一个比较实用、也比较时髦的手术及研究项目。结合我院已完成的 2例肝移植手术 ,简要介绍肝移植手术术前、术中及术后的相关问题 ,并介绍肝移植手术的主要步骤 ,叙述手术中的相关配合问题