原位肝移植治疗终末期自身免疫性肝病

目的 评价肝移植治疗终末期自身免疫性肝病的疗效并总结临床经验.方法 回顾性分析2003年9月至2009年7月间因终末期自身免疫性肝病接受肝移植手术的11例患者的临床资料,其中8例为原发性胆汁性肝硬化,2例为自身免疫性肝炎,1例为原发性硬化性胆管炎.平均年龄为(44.2±8.7)岁.手术方式均采用附加腔静脉整形的改良背驮式肝移植术.术后免疫抑制治疗采用他克莫司或环孢素A联合激素的二联免疫抑制方案,部分患者使用骁悉和熊去氧胆酸.结果 本组11例患者中2例原发性胆汁性肝硬化患者死亡,其中1例于术后第5天死于肺部感染和多器官功能衰竭,另1例于术后964 d死于脓毒症和移植肝失功.5例患者术后1个月内出现急性排斥反应,加强免疫抑制治疗后痊愈.9例患者生存良好并存活至今,随访期7～62个月,中位随访时间为38个月.受体1年存活率为91%,3年存活率为82%,最长存活期5年.随访期间未发现复发病例.结论 肝移植是治疗终末期自身免疫性肝病的惟一有效手段,手术时机的正确把握和有效的免疫抑制治疗是减少肝移植术后并发症的关键.

Abstract：

Objective To evaluate the effect of liver transplantation for end-stage autoimmune liver disease (ESALD) and summarize the clinical experience of liver transplantation in the treatment of ESALD.Methods The clinical data of 11 ESALD cases who underwent liver transplantation from September 2003 to July 2009 were analyzed retrospectively. There were 2 males and 9 females ( median age, 44. 2 ± 8. 7years). The indication of liver transplantation was end stage of primary biliary cirrhrosis (8 cases),autoimmune hepatitis (2 cases), and primary sclerosing cholangitis ( 1 case). In all cases, modified piggyback liver transplantation with venacavaplasty was carried out. Postoperatively all patients were treated with immunosuppressive agents including tacrolimus (or cyclosporine A) and prednisone, some patients were treated additionally with mycophenolate mofetil and ursodeoxycholic acid. Results Postoperatively 2patients of primary biliary cirrhosis died, one of lung infection and multiple organ failure on the 5th postoperative day, the other dying of sepsis and graft dysfunction on the 964th postoperative day. Five cases suffered from episodes of acute cellular rejection within 1 month after transplantation and was successfully reversed by strengthened immunosuppressive therapy. Nine patients recovered satisfactorily and with excellent life quality until now. Patients were followed up from 7 months to 62 months with the median follow-up time of 38 months. The recipient survival rate at 1 year and 3 years was 91% and 82% ,respectively. One patient has now survived for 5 years. No recurrent ALD case was found during follow up.Conclusions Orthotopic liver transplantation is an exclusive treatment for ESALD. Optimum operation timing and effective immunosuppressive treatment are very important for decreasing occurrence of complications.     

影响肝移植术后新发糖尿病逆转的相关因素

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

影响肝移植术后新发糖尿病逆转的相关因素

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

己酮可可碱对大鼠肝脏缺血再灌注损伤的影响

目的:探讨TNF-α抑制剂己酮可可碱对大鼠肝脏缺血再灌注损伤(HIRI)的影响.方法:持续阻断肝固有动脉1 h后再灌注1 h,建立SD大鼠HIRI模型.24只雄性SD大鼠随机分成4组:生理盐水腹腔预处理假手术组(A)、己酮可可碱腹腔预处理假手术组(B)、生理盐水腹腔预处理HIRI组(C)、己酮可可碱腹腔预处理HIRI组...     

肝移植术后患者家属抑郁状况及原因分析

目的 探讨肝移植术后患者家属的抑郁状况及其影响因素. 方法 用抑郁自评量表(SDS)选取自2005年1月至2008年12月接受肝移植术并随访的患者家属50人,与国内SDS常模进行比较. 结果 50名肝移植术后患者家属SDS评分为39.06±11.20,高于国内SDS常模的评分(33.46±8.55),差异有统计学意义(P＜0.05);其中无抑郁者为41人,轻度抑郁6人,中度抑郁3人,抑郁的发生率为18％. 结论 肝移植术后患者家属的抑郁水平高于一般人群,应受到肝移植医师的关注.     

CTLA4Ig和CD40LIg基因修饰骨髓间充质干细胞在异种胰岛移植排斥反应中的作用

目的探讨细胞毒性T淋巴细胞相关抗原4免疫球蛋白(CTLA4Ig)和T细胞分化群40补体免疫球蛋白(CD40LIg)基因修饰骨髓间充质干细胞(MSCs)在异种胰岛移植排斥反应中的作用及其可能的机制。方法将SD大鼠胰岛细胞移植到Wistar糖尿病大鼠肾包膜下,建立SD-Wistar大鼠的异种胰岛移植模型,用携带CTLA4Ig和CD40LIg基因重组腺病毒感染的MSCs进行干预治疗。取造模成功的糖尿病大鼠45只,按随机数字表法分为3组(每组15只):对照组只植入胰岛细胞;单纯MSCs组植入胰岛细胞和MSCs;基因转染MSCs组植入胰岛细胞及CTLA4Ig和CD40LIg基因转染的MSCs。观察胰岛移植后糖尿病大鼠的生存情况、血糖变化和移植物病理形态学的改变,检测移植物CTLA4Ig、CD40LIg和胰岛素的表达以及胰岛移植大鼠细胞因子水平的变化。结果①糖尿病大鼠血糖在移植后2 d降至正常,对照组血糖平均在移植后8 d升高,单纯MSCs组和基因转染MSCs组血糖分别在21 d和49 d升高。②对照组、单纯MSCs组和基因转染MSCs组,移植物存活时间分别为(10.2±2.1)、(23.5±6.8)和(52.1±7.3...     

影响良性终末期肝病肝移植术后远期死亡的预后因素分析

目的: 分析良性终末期肝病肝移植患者术后中远期的生存情况和导致中远期生存率下降的预后因素。 方法: 回顾性地分析2003年10月至2008年6月在我院行原位肝移植手术,且术后存活超过1年的221个良性终末期肝病受者的资料,选取包括受者术前变量、供者变量、术中变量和受者术后变量共27个可能影响患者长期存活的危险因素,采用Cox回归分析,筛选出影响肝移植受者长期存活的独立危险因素。 结果: 221个受体中有28人在术后1年后死亡,主要死亡原因和相关死亡率为：感染、胆道并发症、HBV复发/再感染。保留在Cox回归方程内的协变量为：高龄、ABO血型、冷缺血时间、术后感染部位和胆道并发症。 结论: 良性终末期肝病的移植患者的中远期死亡原因主要是感染、胆道并发症和HBV复发/再感染。影响受者术后中远期存活的危险因素包括高龄（≥60y）,ABO血型（血型不符）,冷缺血时间（＞12h）,术后感染部位（肺部感染）和胆道并发症（移植肝胆管弥漫性狭窄）。术前严格筛选高龄患者,选择ABO血型相同或相符的供者,缩短冷缺血时间,积极防治术后感染和胆道并发症,将有助于提高受者术后中远期存活。     

小肠远端缺血预处理对大鼠肝脏热缺血再灌注损伤的保护作用

目的 观察小肠远端缺血预处理对大鼠肝脏热缺血再灌注损伤的保护作用.方法 将40只Wistar大鼠被随机分为4组:假手术组(Sham)、单纯远端缺血预处理组(RJPC)、单纯缺血再灌注组(IR)和远端缺血预处理+缺血再灌注组(RIPC+IR).远端缺血预处理方式采用于小肠系膜根部游离动脉血管并夹闭5 min后开放5 min,反复3次.缺血再灌注模型采用于肝蒂阻断肝脏供血45 min,阻断范围占整个肝脏的70%,开放复流3 h.检测血液中谷丙转氨酶(ALT)、乳酸脱氢酶(LDH)、一氧化氮(NO)和内皮素(ET)、肝脏苏木素-伊红(HE)病理、心血管指标.结果 复流3 h后,RIPC+IR组的ALT、LDH、心血管指标[平均动脉血压(MAP)、外周血氧饱和度(SaO2)]为(434.26±133.42)U/L、(2536±181)U/L、(83.1±7.3)mm Hg(1 mm Hg＝0.133 kPa)和(97.4±0.5)%,明显好于IR组(953.64±114.12)U/L、(5734±296)U/L、(67.1±7.4)mm Hg和(93.1±0.6)%(P<0.05).RJPC+IR组肝脏HE病理改变程度比IR组小.门静脉中IR组血清NO浓度(15.54±2.34)μmoL/L低于RIPC+IR组(18.10±1.82)μmol/L(P<0.05),外周血中,IR组血浆ET浓度(672.4±63.1)ng/L高于RIPC+IR组(451.7±63.6)ng/L(P<0.05),门静脉中IR组血清ET浓度(612.5±48.2)ng/L高于RIPC+IR组(401.5±51.2)ng/L(P<0.05).结论 小肠RIPC可以减轻肝脏缺血再灌注损伤,具有简便、易操作的特点,NO及ET可能在其中发挥了重要作用.     

基因转移CTLA4Ig和CD40LIg在大鼠异种胰岛移植排斥反应中的作用

目的 探讨基因转移细胞毒性T细胞相关抗原4免疫球蛋白（CTLA4-Ig）和T细胞分化群40L免疫球蛋白（CD40L-Ig）在异种胰岛移植排斥反应中的作用及其机理。方法 建立大鼠-小鼠异种胰岛移植模型,用携带CTLA4-Ig和CD40L-Ig基因的重组腺病毒感染移植胰岛细胞,观察糖尿病小鼠胰岛移植后血糖变化、生存情况及移植物病理形态学改变,检测移植物CTLA4-Ig、CD40L-Ig、胰岛素的表达和移植小鼠白细胞介素2（IL-2）、肿瘤坏死因子（TNF-α）的水平变化。结果 （1）糖尿病小鼠移植后2 d血糖降至正常,对照组(A)血糖平均在移植后8 d升高,CTLA4Ig转染组(B)、CD40LIg转染组(C)和联合转染组(D)血糖分别在24、21和68 d升高。（2）对照组、CTLA4Ig转染组、CD40LIg转染组和联合转染组的移植物存活时间分别为(8.2±0.9) d,(28.7±4.0) d,(26.6±3.2) d 和 (73.6±9.8) d,联合转染组较对照组、CTLA4Ig转染组和CD40LIg转染组显著延长（P<0.01）;CTLA4Ig转染组和CD40LIg转染组较对照组显著显著延长（P<0.01）。（3）对照组在移植后1周内,IL-2、TNF-α的水平均急剧上升,较移植前显著升高（P < 0.01）。（4） 各治疗组移植物见成片的胰岛细胞团,未见淋巴细胞浸润,可见胰岛素、CTLA4Ig和CD40LIg的表达。结论 基因转移CTLA4-Ig和CTLA4-Ig均可抑制异种胰岛移植排斥反应,二者联合效果优于单独使用。