肝移植术后肝动脉并发症的再次肝移植治疗

目的 探讨再次肝移植治疗肝移植术后肝动脉并发症的可行性及手术时机.方法 回顾性分析2003年12月至2006年12月收治的13例肝动脉并发症患者再次肝移植的临床资料.结果 再次肝移植的无肝期、手术时间和首次移植比较差异无统计学意义(P=0.291,P=0.312),术中出血量、ICU停留时间和首次移植比较差异有统计学意义[(3.1±1.1)L比(1.5±0.9)L(P=0.005),(4.3±1.8)d比(3.2±2.5)d(P=0.015)].围手术期病死率为38.5%(5/13),其中移植间隔1个月内死亡1例(1/4),超过1个月死亡4例(4/9).死亡原因分别为急性肾功能衰竭2例、严重感染2例、心肌梗死1例.8例存活,随访6～51个月,中位生存时间22.5个月.结论 再次肝移植是治疗肝移植术后肝动脉并发症导致不可逆性肝功能损害时的惟一有效手段.选择适宜的手术时机和手术方式、调整免疫抑制方案、加强围手术期管理是提高再次肝移植疗效的关键.     

恩替卡韦对肝移植受者血清及外周血单个核细胞内HBV DNA的抑制作用

目的 研究恩替卡韦对乙型肝炎相关性终末期肝病患者肝移植术后血清及外周血单个核细胞（PBMC）内HBV DNA的抑制作用. 方法 选取从2007年8～12月的20例HBsAg阳性肝移植受者作为研究对象（围手术期组）,给予口服恩替卡韦每天0.5 mg联合肌注乙肝免疫球蛋白作为HBV再感染的预防方案,分别于术前1 d和术后1、4、12周采用实时荧光定量PCR法检测血清及PBMC内HBV DNA定量.同时回顾性分析2006年8月至2007年8月共34例行同种异体原位肝移植,术后长期使用恩替卡韦联合肌注乙肝免疫球蛋白的患者（随访组）,随访时间4.0～22.5个月,同样的方法检测血清及PBMC内HBV DNA定量.结果 20例受者血清HBV DNA在恩替卡韦治疗12周时全部转阴.术前1 d和术后1、4、12周PBMC内HBV DNA阳性率分别为85.0%（17/20）和45.0%（9/20）、45.0%（9/20）、40.0%（8/20）,术后1周与术前比较差异有统计学意义（P=0.004）,但1周以后阳性率无显著变化;围手术期PBMC内HBV DNA定量均值分别为104.07±2.07和101.69±1.96、101.51±1.72、101.30±1.63拷贝/106细胞,同样术后1周与术前比较差异有统计学意义（P=0.01）,但随术后时间的延长,下降趋缓,术后4周后定量值的下降差异无统计学意义（P〉0.05）.随访组平均随访13.6个月,均未发现HBV再感染（血清HBV DNA均阴性）,PBMC内HBV DNA阳性率为32.4%（11/34）,定量均值101.03±0.26拷贝/106细胞.结论 恩替卡韦对肝移植术后血清及PBMC内HBV DNA均具有较好的抑制效果,但PBMC内HBV DNA下降趋势在术后4周后即维持在相对稳定状态,不能完全被清除.     

一种预测肝癌肝移植术后肿瘤复发的术前评分模型

目的 建立一种基于外周血中性粒细胞/淋巴细胞比(NLR)的肝癌肝移植适应证评分模型,评价其预测肝癌肝移植术后肿瘤复发的价值.方法 回顾性分析我院76例有完整随访资料的乙型肝炎相关性肝细胞癌患者临床资料.把肿瘤数目＞3、大血管侵犯和NLR≥2.5三个影响肿瘤复发的术前指标分别赋值1分建立预测复发评分模型,评价该评分模型预测肝癌肝移植术后肿瘤复发的价值.结果 预测复发评分模型ROC曲线下面积(AUC)为0.758.2分和3分的患者肝移植术后肿瘤复发的风险比(HR值)分别是10.038和59.773,10例3分的患者都在6个月内肿瘤复发;0分、1分、2分的患者1年、3年、5年的无瘤生存率分别为95.0％、78.4％、78.4％,76.9％、66.9％、63.2％和51.9％、8.7％、8.7％.无大血管侵犯的55例患者中,5例肿瘤数目＞3且NLR≥2.5的患者都在31个月内肿瘤复发.结论 肿瘤数目＞3且术前NLR≥2.5的患者肝移植术后肝癌复发的风险显著增加.该术前预测复发评分模型可作为肝癌肝移植适应证选择的重要参考.     

乙肝患者肝移植术后免疫抑制治疗下拉米夫定耐药的发生和治疗

目的探讨乙肝患者肝移植术后在免疫抑制治疗下拉米夫定耐药的发生、处理及疗效。方法对2003年10月至2005年3月因乙肝相关性终末期肝病在我院接受肝移植并完整随访1年以上的157例患者的临床资料进行回顾性分析,观察并总结肝移植术后,在免疫抑制状态下拉米夫定耐药病例的发生、处理和疗效。结果肝移植术后随访1年以上共发现11例患者出现拉米夫定耐药,其中10例出现在术后1年内,肝移植术后1年的拉米夫定耐药率是6．37％,出现拉米夫定耐药时采用联合新的核苷类似物阿德福韦、恩替卡韦可以有效控制乙肝病毒的复制、改善肝功能;治疗12周、24周和48周时HBV-DNA转阴率分别为27．3％、36．6％、62．5％,下降幅度分别为log DNA (3．85±0．79)、log DNA(3．27±0．84)、log DNA(3．19±0．58),HBeAg阳性血清HBeAg的血清转换率为18．2％、27．3％、50．0％。结论拉米夫定联合小剂量乙肝免疫球蛋白可以有效推迟肝移植术后免疫抑制治疗下拉米夫定耐药出现的时间,联合新的核苷类似物抗病毒药物对肝移植术后出现的拉米夫定耐药的乙肝病毒疗效确切。     

供肝动脉变异和植入前动脉重建

目的探讨供肝动脉变异类型,术中损伤原因及植入前重建的方法。方法1993年10月至2004年12月,中山大学附属第三医院肝脏移植中心共行供肝切取和修整术600例,术中记录肝动脉变异类型和术中动脉误伤,重建变异肝动脉,形成单一的备吻合血管。结果在600例供肝中,19·2%(115/600)供肝动脉变异。53例(53/600)变异动脉须血管重建,其中39例(39/53)代替性或副肝右动脉来自肠系膜上动脉,1例(1/53)代替性肝右动脉来自腹腔干,5例(5/53)代替性或副肝左动脉来自胃左动脉,2例(2/53)变异肝左动脉和3例(3/53)变异肝右动脉离断后来源不清,3例(3/53)变异肝左和肝右动脉双重替代。6例(6/485)供肝切取术中意外损伤正常肝动脉,需要动脉重建。变异肝动脉损伤19例(19/115),均行动脉重建。动脉重建方法包括变异动脉与脾动脉(36/53)、胃十二指肠动脉(12/53)以及复杂的吻合方法(5/53)。结论供肝快速切取过程中,肝动脉变异增加肝动脉意外损伤发生率,损伤变异动脉均须在植入前重建。变异动脉重建方法的选择取决于肝动脉解剖学特点。     

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。     

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.