ABCB1基因多态性对肝移植后他克莫司用量的影响

背景:钙神经素抑制剂他克莫司被广泛用于移植后预防排斥反应的发生,但其治疗窗狭窄,且药代动力学个体差异较大.目的:观察ABCB1基因多态性对肝移植患者移植后早期免疫抑制剂他克莫司的用量及C/D比值的影响.方法:选择2008-01/2010-09-31在昆明市第一人民医院暨昆明医学院附属甘美医院肝胆外科接受原位肝移植患者67例,通过检测67例肝移植受者移植后不同时间他克莫司的血药浓度及其用量,并利用DNA直接测序检测受体ABCB1的基因多态性,分析肝移植后免疫抑制剂他克莫司的用量及其血药浓度与ABCB1基因多态性的关系.结果与结论:肝移植后他克莫司的口服需药量在个体间存在很大差异,67例肝移植患者中,ABCB1不同位点的基因多态性分布不同,其中仅ABCB1 3435C>T基因多态性与他克莫司用量有关.提示ABCB1的基因多态性可能是患者肝移植后他克莫司药代动力学显著个体差异的重要因素,ABCB1 3435C>T野生型的患者需要更高剂量的他克莫司便可达到目标血药浓度水平,检测ABCB1的基因多态性可以优化肝移植后免疫抑制剂的个体化治疗方案.     

酶放大免疫法测定他克莫司血药浓度的临床应用

目的 探讨酶放大免疫法测定他克莫司（FK506）血药浓度的方法学评价和临床应用的可行性.方法 对酶放大免疫法测定他克莫司血药浓度的回收率、精密度、线性范围等方法学指标进行测定.并对1 255例次肝肾移植术后进行他克莫司血药谷浓度测定,进行相关的统计学分析.结果 方法回收率为98.2%~101.03%,批内精密度的平均CV为5.07%,日间精密度的平均CV为6.79%,线性范围2.0~30.0 ng/mL.1 255例次治疗抗移植排斥反应FK506的血药浓度为3.0~12.9 mg/mL,占测定数的91.16%.结论 酶放大免疫法测定他克莫司血药浓度具有准确、稳定、简便、快速、自动化等优点,适用临床他克莫司血药浓度监测.在患者临床状况良好下,他克莫司浓度为3.0~12.9 ng/mL为适合的治疗血药浓度.     

ABCB1基因多态性对肝移植后他克莫司用量的影响

背景：钙神经素抑制剂他克莫司被广泛用于移植后预防排斥反应的发生,但其治疗窗狭窄,且药代动力学个体差异较大。目的：观察ABCB1基因多态性对肝移植患者移植后早期免疫抑制剂他克莫司的用量及C/D比值的影响。方法：选择2008-01/2010-09-31在昆明市第一人民医院暨昆明医学院附属甘美医院肝胆外科接受原位肝移植患者67例,通过检测67例肝移植受者移植后不同时间他克莫司的血药浓度及其用量,并利用DNA直接测序检测受体ABCB1的基因多态性,分析肝移植后免疫抑制剂他克莫司的用量及其血药浓度与ABCB1基因多态性的关系。结果与结论：肝移植后他克莫司的口服需药量在个体间存在很大差异,67例肝移植患者中,ABCB1不同位点的基因多态性分布不同,其中仅ABCB1 3435C〉T基因多态性与他克莫司用量有关。提示ABCB1的基因多态性可能是患者肝移植后他克莫司药代动力学显著个体差异的重要因素,ABCB1 3435C〉T野生型的患者需要更高剂量的他克莫司便可达到目标血药浓度水平,检测ABCB1的基因多态性可以优化肝移植后免疫抑制剂的个体化治疗方案。     

他克莫司和西罗莫司对行肝癌肝移植患者Foxp3~+调节性T细胞产生及肝癌复发的影响

背景:通过促进调节性T细胞的产生及增强其功能的发挥已成为维持移植物免疫耐受的有效手段。目的:探讨他克莫司和西罗莫司对行肝移植的肝癌患者Foxp3+调节性T细胞产生及肝癌复发的影响。方法:纳入符合米兰标准的肝癌肝移植患者40例,随机分为西罗莫司组和他克莫司组,每组20例,移植后第2~12个月间每月抽取受试者外周血检测Foxp3+调节性T细胞,并行彩超和外周血检测甲胎蛋白,必要时肝穿刺活检观察排斥反应及肿瘤的复发情况。结果与结论:流式细胞仪检测结果显示,西罗莫司组外周血Foxp3+调节性T细胞阳性率明显高于他克莫司组(P<0.05),移植肝穿刺活检证实西罗莫司组排斥反应与他克莫司组差异无显著性意义(P>0.05),而移植肝彩超、外周血甲胎蛋白检测及移植肝穿刺活检或手术亦证实在肝癌复发率方面西罗莫司组明显低于他克莫司组(P<0.05)。说明西罗莫司在肝癌肝移植中对肿瘤复发的抑制作用方面优于他克莫司,且排斥反应较他克莫司并未增加,甚至有更好的免疫耐受效果。     

他克莫司个体内变异性与心脏移植预后的相关性分析

目的 评价他克莫司个体内变异性(IPV)与心脏移植术后感染、排斥及死亡的相关性。方法 收集2018年4月至2021年10月郑州市第七人民医院心脏移植受者术后第3～6个月的他克莫司谷浓度(C0),剂量校正后计算他克莫司IPV,根据平均值分为高IPV组和低IPV组,比较两组受者预后差异。结果 共纳入102例受者,IPV平均值为26.8%。相对于低IPV组,高他克莫司IPV组的至少一次C0在治疗目标(8～12 ng/mL)范围之外的受者比例更高(<8 ng/mL:80.5%vs. 39.3%,χ²=16.836,P <0.001;> 12 ng/mL:85.4%vs. 47.5%,χ²=15.007,P <0.001)。高IPV组受者的感染发生率高于低IPV组(34.2%vs.16.4%),率差及95%置信区间为17.8%(0.52%～34.99%),差异有统计学意义(χ²=4.295,P=0.038)。排斥反应和死亡方面,两组组间比较差异无统计学意义(均P> 0.05)。感染、排斥或者死亡其中之...     

肾移植后他克莫司与五酯胶囊合用致高血钾症1例

背景:肾移植患者由于免疫抑制剂的药物肝毒性,肝功能异常发生率高,对临床出现肝功能异常者,需护肝治疗.但合用护肝药必须监测免疫抑制剂浓度.目的:探讨肾移植患者他克莫司与五酯胶囊合用对他克莫司浓度及血生化的的影响.方法:回顾性分析1例以他克莫司为免疫抑制剂的肾移植患者加服及停用五酯胶囊时他克莫司浓度及肾功能、血生化变化.患者因"慢性肾小球肾炎,慢性肾功能不全"于1998-06起行血液透析治疗.2000-08行同种异体尸体肾移植,移植后免服他克莫司+吗替麦考酚酯+泼尼松.移植后4个月患者出现肝功能异常,加用联苯双酯.2010-07-25患者停用联苯双酯,改服五酯胶囊.2010-07-29患者停用五酯胶囊.结果与结论:服用他克莫司的肾移植受者,合用五酯胶囊,他克莫司血浓度显著升高.由5.3 ng/L升至24.7 ng/L,并合并高血钾症,停用五酯胶囊1周,他克莫司浓度由24.7 ng/L.降至6.1 ng/!.,血钾由6.4 mmol/L.降至4.6 mmol/L.提示移植肾功能稳定的肾移植受者,在加用五酯胶囊,必须严密监测他克莫司血浓度及肝肾功能、电解质,及时调整他克莫司片用量,保护移植肾功能.     

他克莫司在体外对HepG2.2.15细胞增殖及乙型肝炎病毒复制的影响

背景:肝癌复发与乙肝病毒再感染两者关系尚不明确,有人认为与肝移植后免疫抑制剂应用有关.目的:观察他克莫司在体外对肝癌HepG2.2.15细胞增殖及对细胞内乙肝病毒复制的影响.方法:选择肝癌HepG2.2.15细胞进行体外培养,第3代细胞培养24 h后加他克莫司进行干预,0 g/L他克莫司作为对照组,50 g/L 他克莫司为低浓度组,100,500 g/L他克莫司为中浓度组,1 000,3 000 g/L他克莫司为高浓度组.结果与结论:①中、高浓度的他克莫司对HepG2.2.15细胞有增殖抑制作用,低浓度无抑制作用,且有相关性.②高浓度他克莫司作用时使HepG2.2.15细胞停止在G0/G1期.③他克莫司可以使HepG2.2.15细胞中CyclinA表达降低,且呈浓度依赖性,他克莫司浓度越高,CyclinA表达越少.④他克莫司作用HepG2.2.15细胞,对HBV的复制无影响.结果说明他克莫司在体外对HepG2.2.15增殖有抑制作用,其中CyclinA可能发挥一定的作用,而对乙肝病毒复制没有影响.     

DA至Lewis大鼠肝移植急性排斥反应模型的建立:技术改良分析

背景:国际上研究肝移植免疫耐受的基础动物模型是大鼠肝移植急性排斥反应模型,国际上公认的肝移植急性排斥反应模型鼠种配对方式为DA至Lewis大鼠、DA至BN大鼠及BN至Lewis大鼠,但由于鼠种缺乏和操作技术有待成熟的原因,国内较少引用以上鼠种配对方式进行该模型的建立。目的:课题组在大量SD大鼠肝移植模型建立训练的基础上,采用DA大鼠为供体,Lewis大鼠为受体,摸索DA至Lewis大鼠肝移植急排模型建立技巧和经验。方法:通过改良二袖套法,以雄性DA大鼠为供体,雄性Lewis大鼠为受体,建立原位肝移植动物模型60只,受体大鼠术前1d和术后1周内饲喂治疗剂量的他克莫司,1周后半量递减并停药,记录移植手术时间,观察受体大鼠的术后生存状况、手术成功率及生存期,分别于术后7,14,21,28d处死受体大鼠,获取肝组织标本,苏木精-伊红染色,观察肝脏大体和镜下的病理学变化,进行急性排斥反应评分。结果与结论:供肝冷缺血时间30～60min,供体手术时间(18.5±4.0)min,供肝修整时间(7±3)min,受体手术时间(35.0±7.3)min,无肝期为(13.0±3.0)min,手术成功率为98%,1周存活率为91.6%。术后2周随着他克莫司撤药,受体大鼠迅速发生急性排斥反应,于术后14～28d死亡,平均生存时间为(20.85±0.71)d,中位生存时间为21d。实验建立DA至Lewis大鼠肝移植急性排斥反应动物模型需要以大量SD大鼠肝移植训练为基础进行,通过对二袖套法技术的改良和围手术期短期应用他克莫司有助于该模型的稳定建立。     

肾移植后他克莫司与五酯胶囊合用致高血钾症1例

背景：肾移植患者由于免疫抑制剂的药物肝毒性,肝功能异常发生率高,对临床出现肝功能异常者,需护肝治疗。但合用护肝药必须监测免疫抑制剂浓度。目的：探讨肾移植患者他克莫司与五酯胶囊合用对他克莫司浓度及血生化的的影响。方法：回顾性分析1例以他克莫司为免疫抑制剂的肾移植患者加服及停用五酯胶囊时他克莫司浓度及肾功能、血生化变化。患者因＂慢性肾小球肾炎,慢性肾功能不全＂于1998-06起行血液透析治疗。2000-08行同种异体尸体肾移植,移植后免服他克莫司＋吗替麦考酚酯＋泼尼松。移植后4个月患者出现肝功能异常,加用联苯双酯。2010-07-25患者停用联苯双酯,改服五酯胶囊。2010-07-29患者停用五酯胶囊。结果与结论：服用他克莫司的肾移植受者,合用五酯胶囊,他克莫司血浓度显著升高。由5.3ng/L升至24.7ng/L,并合并高血钾症,停用五酯胶囊1周,他克莫司浓度由24.7ng/L降至6.1ng/L,血钾由6.4mmol/L降至4.6mmol/L。提示移植肾功能稳定的肾移植受者,在加用五酯胶囊,必须严密监测他克莫司血浓度及肝肾功能、电解质,及时调整他克莫司用量,保护移植肾功能。     

肝肾联合移植患者免疫抑制剂的应用

背景:不同单一器官移植后调动机体免疫反应的力度各不相同,故其免疫抑制剂的应用种类及剂量有所差异,多器官联合移植工作中,免疫抑制剂的应用则更为复杂,是移植工作者需要逐步总结的经验之一.目的:探讨肝肾联合移植患者合理的免疫抑制剂应用方案.方法:选择解放军第309医院器官移植中心2002-04/2009-07肝肾联合移植患者10例,以单独肝移植及肾移植患者为对照.3组患者术后早期抗排斥治疗均采用以他克莫司为基础的三联免疫抑制方案,在此方案基础上同时应用巴利昔单抗诱导疗法.肝肾联合移植组和肝移植组患者术中给予甲基泼尼松龙500mg冲击,术后第1天激素用量为160mg,分2次给药,此后每日递减40mg,术后第5天改为20mg泼尼松口服,术后2个月停用激素,术后6个月停用霉酚酸酯,仅应用他克莫司抗排斥治疗;肾移植组术中给予甲基泼尼松龙1000mg冲击,术后前3d应用甲基泼尼松龙500mg,此后每日50mq泼尼松口服,逐渐递减至每日10mg长期维持,术后长期应用他克莫司、霉酚酸酯和糖皮质激素.结果与结论:肝肾联合移植患者术后早期及术后6个月他克莫司用量同肝移植患者相近(P＞0.05),但低于肾移植患者(P＜0.05,P＜0.01):肝肾联合移植和肝移植患者激素和霉酚酸酯用量亦明显低于肾移植患者,并且均在半年内停用激素和霉酚酸酯,肾移植患者需长期应用.3组病例1年后维持用药逐渐体现出个体差异现象.肝肾联合移植组均未出现远期肝功能异常,同时低剂量抗排斥药物对患者免疫系统影响较小,围手术期感染发生率明显减低.说明肝肾联合移植患者免疫抑制剂早期的应用参考单肝移植患者即可达到满意的治疗效果,激素和霉酚酸酯可在6个月内停药,他克莫司用量可低于单肾脏移植患者.     

The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications

Introduction: Artificial liver support systems represent a potential useful option for the treatment of liver failure. The outcomes of patients treated with the fractionated plasma separation and adsorption (FPSA) system are presented. Patients and methods: FPSA was performed 85 times for 27 patients (median 3 treatments/patient) with liver failure [85.2% acute liver failure (ALF) and 14.8% acute‐on‐chronic liver failure] using the Prometheus 4008H (Fresenius Medical Care) unit. Citrate was used for anticoagulation. A variety of clinical and biochemical parameters were assessed. Comparisons between pretreatment and post‐treatment data were performed using paired t‐test. Results: The 85 sessions had a mean duration of 6 h. There were significant decreases in total bilirubin (13.18 ± 9.46 mg/dL vs. 9.76 ± 7.05 mg/dL; P < 0.0001), ammonia (167.6 ± 75 mg/dL vs. 120 ± 43.8 mg/dL; P < 0.0001), blood urea nitrogen (BUN; 12.55 ± 13.03 mg/dL vs. 8.18 ± 8.15 mg/dL; P < 0.0001), creatinine (0.54 ± 0.47 mg/dL vs. 0.46 ± 0.37 mg/dL; P = 0.0022) levels, and in pH (7.48 ± 0.05 vs. 7.44 ± 0.08; P = 0.0045). Four patients (14.8%) received liver transplantation after the treatments; in nine patients, transplantation was not necessary anymore (33%); the remaining 14 patients did not receive a transplantation because they were either not appropriate candidates or no organ was available. Overall survival was 48.1% (4 transplanted and 9 treated patients). No hematological complications related to FPSA were observed. Conclusions: FPSA system is a safe and effective detoxification method for patients with liver dysfunction, including ALF. The system is useful as a symptomatic treatment before liver transplantation; in up to 1/3 of the cases, it can even be used as a sole method of treatment. J. Clin. Apheresis 25:195–201, 2010. © 2010 Wiley‐Liss, Inc.     

重型肝炎和肝癌肝硬化患者肝移植围手术期肾功能的变化

目的 观察重型肝炎及肝癌肝硬化患者原位肝移植围手术期肾功能变化,评价肝移植术对该类患者肾功能的影响。方法 选择30例术前血肌酐（SCr）、尿素氮（BUN）正常的终末期肝病、行背驮式原位肝移植术患者,手术过程中均未采用体外静-静脉转流。按原发病不同分为重型肝炎组（15例）和肝癌肝硬化组（肝癌组15例）,分别于术前（麻醉后）、无肝前20min、无肝30min、新肝60min、术毕不同时间点取桡动脉血,测定β2-微球蛋白（β2-MG）值,并记录血流动力学变化;分别于术前、新肝60min、术毕留取新鲜尿液,测定尿β2-MG及尿N-乙酰-β-D-葡萄糖苷酶（NAG）值。记录两组患者术前、术后24h、术后1周的SCr、BUN值以及术后肝移植相关性肾功能衰竭（肾衰）的发生情况。结果1术前重型肝炎组有7例血β2-MG、12例尿β2-MG、14例尿NAG值均高于正常参考值;而肝癌组仅有3例血β2-MG、3例尿β2-MG、7例尿NAG值高于正常参考值;两组各时间点血β2-MG异常率比较差异均无显著性（P均〉0.05）;重型肝炎组术前尿β2-MG及NAG异常率明显高于肝癌组（P〈0.01和P〈0.05）。2术中两组血β2-MG值与术前比较变化不大,变化趋势两时间点间比较差异均无显著性;两组新肝期60min及术毕尿β2-MG及NAG均较术前呈增高趋势,但差异无显著性（P均〉0.05）,而重型肝炎组各时间点尿NAG值明显高于肝癌组（P〈0.05或P〈0.01）。3重型肝炎组肝移植相关性肾衰发生率为46.7%,而肝癌组无一例发生（P〈0.01）。结论 重型肝炎患者较肝癌肝硬化患者肝移植术后早期易发生急性肾衰,围手术期应注意肾功能保护。     

小儿亲体肝移植急性排斥反应临床特点的初步探讨

摘 要 目的：本课题拟通过回顾性分析,结合小儿的生理免疫特征,比较小儿与成人肝移植急性排斥反应的不同临床特点,以期为小儿肝移植术后个体化抗排斥治疗提供一定的理论依据。材料和方法：收集本院2003年1月至2007年12月小儿部分亲体肝移植18例,其中发生急性排斥反应4例;2003年1月至2007年12月成人全肝改良背驮式肝移植56例,其中发生急性排斥反应9例。术后采用糖皮质激素（甲基强的松龙）和FK506进行免疫抑制治疗。术后监测患儿及成人：①肝功能,主要包括血清总胆红素、直接胆红素,ALT和AST;② FK506血浓度。结果：检测肝穿刺日及之前6d亲体肝移植患儿肝功能的主要指标：AR组中,丙氨酸氨基转移酶（ALT）及天冬氨酸氨基转移酶（AST）在穿刺前3d起较非AR组显著升高（P<0.01）;而总胆红素（TBIL）及直接胆红素（DBIL）水平则在穿刺前第5d起出现显著增高（P<0.01）。成人肝移植AR组中,穿刺日及之前8d,患者外周血中ALT、AST,TBIL及DBIL的水平已均显著高于非AR组（P<0.01）。小儿及成人肝移植患者分别于病理确诊AR前5d及8d起,血中FK506谷浓度较非AR组明显下降（P<0.05）。结论：小儿亲体肝移植术后急性排斥反应的发生时间可能较成人肝移植术后急性排斥反应发生时间晚,程度较成人AR轻,这与小儿亲体肝移植受供体血缘关系近、供肝质量好有关。FK506浓度较低时可能诱发急性排斥反应,但血FK506的浓度高低与急性排斥反应的程度并无显著关联。 关键词：小儿肝移植,急性排斥反应,肝功能。     

Splenomegaly and hypersplenism in cirrhotic patients before and after orthotopic liver transplantation

Spleen length was measured by ultrasound in 15 patients with cirrhosis and portal hypertension before and after orthotopic liver transplantation (OLT). A significant decrease was found in splenic length after OLT (from 179±32 to 149±30 mm, P=0.0001; mean percent decrease=16.7±9.9%). Hypersplenism disappeared in 9/13 cases after transplantation. Mean portal flow velocity was valued in 10/15 subjects before and after OLT. A trend towards increased mean portal flow velocity after OLT was observed (from 16.0±9.0 to 22.3±9.0 cm/s). The correlation between values of mean portal flow velocity measured before and after OLT was not significant (r=0.558, P=0.0939). The same was true for the correlation between mean portal flow velocity and spleen length measured before and after OLT.     

Endothelin-1 and in vitro evidence of renal artery vasoconstriction after liver transplantation

Twelve pigs underwent orthotopic liver transplantation. The mean endothelin-1 (ET-1) levels in the serum samples of the recipient animals 1 h after reperfusion of the graft (6.2±1.5 pg/ml) was significantly higher (P<0.05) than in pretransplantation samples (3.2±0.6 pg/ml). Serum blood urea nitrogen (BUN) 24 h after transplantation was 13.8±5.9 mg/dl, which was significantly higher than before transplantation (6.4±2.2 mg/dl). There was a positive correlation between the serum BUn and ET-1 (r=0.62,P<0.05). An in vitro isometric tension study was performed for the contractility response rate of the intact renal artery in the bath chamber containing the serum of the corresponding recipient animals. The mean contractility response rates were higher with the serum obtained after reperfusion of the graft (66.9±32.4%) than with those obtained before transplantation (18.3±9.2%) when compared to a standard contractility rate of 100% with 40 mM KCl. Moreover, these contractility response rates were significantly reduced (32.8±21.0%) with the addition of the ET-1 receptor antagonist FR139 317. The results of the present study demonstrated that the liver transplantation was associated with elevation of ET-1 in the serum of the recipient animals. It was considered that ET-1 in the serum caused a direct vasoconstriction of the renal artery in vitro. This may help to explain the renal dysfunction that is often seen in the recipients of clinical liver transplantation.     

Dynamic changes in liver function after transjugular intrahepatic portosystemic shunt in patients with cirrhosis

PurposeTo evaluate the dynamic changes in liver function after transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with cirrhosis and to explore its association with clinical outcomes.MethodsThis retrospective study included patients who underwent TIPS between August 2016 and December 2020. Liver function was primarily evaluated using the model for end-stage liver disease (MELD) score, which was analyzed at baseline, 1 week, 1 month, 3 months, 6 months, and 12 months using one-way repeated measures ANOVA. The Kaplan-Meier method, log-rank test, and multivariate analysis were used as appropriate.ResultsIn total, 235 patients were included in this study. The MELD score was significantly higher at 1 week (11.8 ?± ?3.1 vs 13.5 ?± ?3.5, p ?< ?0.05) and 1 month (11.8 ?± ?3.1 vs 13.2 ?± ?4.6, p ?< ?0.05) than the baseline level and recovered at 3 months (11.8 ?± ?3.1 vs 11.9 ?± ?3.9, p ?> ?0.05). At 12 months, the MELD score was higher than the baseline level (11.8 ?± ?3.1 vs 12.4 ?± ?3.2, p ?< ?0.05). Patients with a recovery of the MELD score (n ?= ?151) at 3 months had a lower probability of overt and severe HE (log-rank p ?= ?0.015 and p ?= ?0.027, respectively) than those without recovery (n ?= ?84). Logistic regression analysis revealed that albumin (odds ratio [OR], 0.926; 95% confidence interval [CI], 0.863–0.992; p ?= ?0.029) and platelet count (OR, 0.993; 95% CI, 0.987–0.999; p ?= ?0.033) were independent predictive factors for non-recovery of the MELD score at 3 months.ConclusionsLiver function after TIPS creation showed a trend of deterioration at first, followed by recovery. Recovery of liver function at three months was associated with reduced overt and severe HE.     

Antibody elimination by apheresis in living donor liver transplant recipients.

In the present study, we investigated retrospectively the indications and the efficacy of the elimination of preexisting antiallogeneic antibodies in liver transplant recipients. Three patients who were ABO blood type incompatible were subjected to plasmapheresis and double filtration plasmapheresis before the living donor liver transplantation (LDLTx), and the titers decreased to less than 8. After transplantation, plasmapheresis was also performed in 3 cases, and continuous hemodiafiltration in 1 case, and in 2 out of these 3 patients acute rejection was recognized. Two patients who were crossmatch positive were subjected to plasmapheresis before transplantation, and the T warm titers were reduced to less than Score 2. These 2 patients had no acute rejections after transplantation. We conclude that in liver transplant patients apheresis is effective to prevent acute rejection induced by preexisting anti-A and/or anti-B antibodies and anti-donor specific antibodies before transplantation, but it is not effective in a patient with accelerated humoral rejection occurring after transplantation.     

Intestinal MDR1/ABCB1 level at surgery as a risk factor of acute cellular rejection in living-donor liver transplant patients

BACKGROUND: Although the prevention of immunologic reactions with sufficient immunosuppression prolongs graft and patient survival rates, the large interindividual variation in tacrolimus pharmacokinetics interferes with treatment. In this study we have examined whether intestinal MDR1 (ABCB1) is a potential biomarker predicting the occurrence of acute cellular rejection, as well as a factor to predict absorption of tacrolimus, after living-donor liver transplantation. METHODS: By use of tissue specimens of intestinal mucosa (n = 164) obtained at surgery, the messenger ribonucleic acid (mRNA) expression of intestinal MDR1 and cytochrome P450 (CYP) 3A4 was quantified. RESULTS: The probability of acute cellular rejection during the first 10 days after surgery was significantly associated with the average trough concentration of tacrolimus between postoperative days 2 and 4 (45.1% for <7 ng/mL versus 22.9% for >7 ng/mL,P= .0040). High levels of MDR1 were associated with an episode of acute cellular rejection before postoperative day 10 (odds ratio, 2.306 [95% confidence interval, 1.058-5.028]) and with a poor survival rate during the first postoperative year (odds ratio, 7.413 [95% confidence interval, 1.567-36.073]). The mRNA expression level of MDR1 was inversely correlated with the tacrolimus concentration-oral dose ratio during the initial 4 days after surgery in patients with a graft-to-recipient weight ratio greater than 1.5 (r= -0.6798, P< .0001) and those with a graft-to-recipient weight ratio of less than 1.5 (r= -0.7180, P< .0001). CONCLUSION: The enterocyte MDR1 mRNA level was suggested to be a risk factor for acute cellular rejection and death after surgery. Therefore obtaining a sufficient tacrolimus blood level via this molecular information-based initial dosage adjustment may enable the episode of acute cellular rejection after liver transplantation to be reduced.     

重组人生长激素对肝移植术后早期营养状态及免疫功能影响的前瞻性研究

目的 评价重组人生长激素（rhGH）结合营养支持治疗在肝移植术后早期对患者营养状态及免疫功能的影响,观察其对肝功能、急性排斥反应及感染发生率是否具有影响,以及临床应用的安全性。方法 60例良性终末期肝病患者于肝移植前被随机分为治疗组（n=30）及对照组（n=30）。两组术后均予营养支持及免疫抑制剂治疗,其中治疗组于术后24h给予rhGH（思增）10U/d皮下注射10d。于术后1、4、8和14d采集静脉血,观察转铁蛋白、前白蛋白、白蛋白、尿素氮等营养指标;CD4/CD8、免疫球蛋白G（IgG）、IgM、IgA等免疫指标;生长激素（GH）、胰岛素样生长因子-1（IGF-1）、天冬氨酸转氨酶（AST）、丙氨酸转氨酸（ALT）水平;维持血糖安全范围（8~10mmol/L）所需胰岛素用量;术后28d内急性排斥反应发生率（肝穿活检）及感染发生率。结果与对照组比较,治疗组14d内转铁蛋白、前白蛋白、CD4/CD8、GH、IGF-1水平显著升高（P均〈0.05）,尿素氮水平明显下降（P〈0.05）;治疗组术后4d和8d控制血糖所需外源性胰岛素用量明显大于对照组（P均〈0.05）;术后14d白蛋白使用量明显低于对照组（P〈0.05）;两组14d内AST、ALT水平及28d内急性排斥反应和感染发生率比较差异均无显著性。结论 在使用免疫抑制剂的前提下,rhGH结合营养支持治疗可以加速改善肝移植术后患者的营养不良,未体现提高机体免疫力的优势,对术后移植肝功能恢复、急性排斥反应及感染发生率未见显著影响。由于其所致血糖升高降低了其安全性。     

治疗用脐血干细胞的制备及初步临床应用

目的制备满足临床干细胞治疗需要的脐带血干细胞制剂,观察脐血干细胞局部移植治疗肝硬化失代偿和股骨头坏死的初步临床疗效。方法建立标准化操作规程(SOP),进行脐带血的采集、分离和检测,制备脐带血干细胞制剂进行局部移植。选择进行局部移植干细胞制剂治疗的相关疾病患者共11例,其中肝硬化9例、股骨头缺血坏死2例;年龄30—65岁,平均51岁,男9例,女2例。结果制备的脐带血干细胞制剂有核细胞计数达(3.8±1.73)×109个,均达到治疗剂量,其中CD34+细胞比率为(1.93±0.54)%,CD105+细胞比率为(97.9±4.0)%。肝硬化失代偿期患者治疗后白蛋白水平逐步升高,1个月后与治疗前相比有明显升高(P<0.05)。肝硬化和股骨头缺血坏死患者经治疗后临床症状均有好转。结论脐带血干细胞移植可为临床多种疾病的有效治疗提供一种新手段。