肝肾联合移植13例临床分析

目的 探讨肝肾联合移植的适应证、手术并发症及生存情况.方法 回顾性分析2003年10月至2008年12月施行的13例肝肾联合移植患者的临床资料,分析围手术期死亡率、并发症情况及生存情况.结果 13例肝肾联合移植患者围手术期死亡率30.8%(4/13).术中、术后腹腔出血4例(30.8%);肺部感染7例(53.8%);移植肾急性排斥反应1例(7.7%).本组随访4.4～60个月,中位数40个月.存活1年以上8例,2年以上6例,3年以上5例,4年以上3例,5年以上1例.肝肾联合移植前有1例患者经历肝移植(例2)和2例患者经历肾移植(例3、例4),例4患者于肝肾联合移植术后第29天死于肺部感染、多器官功能衰竭,例2和例3肝肾联合移植术后分别存活40 m、48 m.结论 肝肾联合移植是治疗终未期肝肾疾病的有效方法.肝/肾移植术后再行肝肾联合移植是可行的.

Abstract：

Objective To investigate the indications, complications and survival results of combined liver-kidney transplantation. Methods From Oct 2003 to Dec 2008, the clinical data of 13 patients who underwent combined liver-kidney transplantation (CLKTs) were retrosptiverly analyzed in our institution. The perioperative mortality rate, complications and the result of follow-up were analyzed.Results The perioperative mortality rate (within 30 days) was 30.8% (4/13). Postoperative complications included intrabdominal bleeding in 4 patients ( 30. 8% ); pulmonary infection in 7 patients (53.8%); acute renal rejection in one (7. 7% ). Survivors were followed up from 4.4 to 60 months, with the median time of 40 months. Eight patients have survived more than 1 year; six patients have survived more than 2 years; five of them have survived for more than 3 years; and three of them have survived for more than 4 years, with one surviving for more than 5 years. One patient had undergone liver transplantation ( case 2 ) and two patients had had kidney transplantations ( case 3 and case 4 ) before this CLKTs.Postoperatively case 4 died of pulmonary infection and multiple organ failure at day 29, while case 2 and case 4 survived respectively 40 m, 48 m after CLKTs. Conclusions CLKTs is an effective therapy for end-stage liver and kidney disease. CLKTs for patients with irreversible liver and renal insufficiency after initial liver transplantation or kidney transplantation was feasible.     

终末期良性肝病患者肝移植后免疫抑制治疗单中心经验总结

目的 总结单中心原发病为良性终末期肝病患者肝移植后免疫抑制剂的应用经验,探讨个体化治疗方案.方法 回顾性分析单中心1400例肝移植中645例原发病为良性终末期肝病者的资料.2002年4月至2004年12月为第1阶段(共146例),受者均采用常规三联用药方案,即他克莫司(Tac)+吗替麦考酚酯(MMF)+甲泼尼龙(MP);2005年1月至2007年12月为第2阶段(共273例),受者用药量较前减少;2008年1月至2010年8月为第3阶段(共226例),根据术前终末期肝病模型(MELD)评分及受者状况分为常规组和重症组,采用个体化免疫抑制方案.结果 3个阶段中,MELD评分<25分者的存活率分别为88.9%、94.2%和95.4%,MELD评分≥25分者的存活率分别为67.7%、73.4%和82.0%.3个阶段中MELD评分<25分者排斥反应发生率的差异无统计学意义(P>0.05),MELD评分≥25分者第2阶段和第3阶段排斥反应发生率稍高于第1阶段(P<0.05).结论 肝移植术后免疫抑制剂的应用可根据受者的具体情况进行个体化应用,有利于提高其存活率.

Abstract：

Objective To analyze the individual immunosuppressive protocol (IP) after liver transplantation (LT) in benign end-stage liver disease. Methods The clinical data of 645 patients with benign end-stage liver disease undergoing LT in our institute from April 2002 to Aug 2010 wen analyzed retrospectively. 146 cases from Apr. 2002 to Dec. 2004 were in stage one, and triple therapy containing tacrolimus (Tac), mycophenolate mofetil (MMF) and methylprednisolone (MP) was used;273 cases from Jan. 2005 to Dec 2007 were in stage two, and the less dose of immunosuppressant than stage one was used; 226 cases from Jan. 2008 to Aug. 2010 were in stage three, and they wen divided into conventional group and severe patient group according to their preoperative model for endstage liver disease (MELD) score and patient condition, the individual IP was used. Results The overall survival rate of patients with MELD score <25 was 88. 9 % in stage one, 94. 2 % in stage two, and 95. 4 % in stage three; The overall survival rate of patients with MELD score ≥25 was 67. 7 % in stage one, 73. 4 % in stage two, and 82. 0 % in stage three. The incidence of rejection ir cases with MELD score <25 had no significant difference (P>0. 05). The incidence of rejection in cases with MELD score ≥25 in stage two and stage three was higher slightly than in stage one (P<0. 05). Conclusion The IP after liver transplantation should be individualized according to recipient conditions, which can increase survival rate.     

活体肝移植供体术后早期肝功能恢复的研究

目的 探讨不同移植肝类型的活体肝移植供体术后早期肝功能的变化规律和并发症发生率.方法 对四川大学华西医院2002年1月至2009年5月154例活体肝移植供体的资料进行前瞻性的收集和登记,依据移植肝类型分为右叶肝供体组141例(R组)和左叶肝供体组13例(L组),对其术后肝功能指标和并发症进行比较分析.结果 R组实际切取的供肝重量大于L组(t=11.418,P＜0.05),R组残余肝重量小于L组(t=-5.040,P＜0.05)、残余肝重量/标准肝重量(%)小于L组(t=-10.841,P＜0.05).除R组TB峰值出现在术后第3天外,L组的TB和两组中的ALT、AST、INR的峰值均出现在术后第1天,此后这些指标均向正常参考值方向下降.术后第1、3、7天R组的TB高于L组(分别t1=5.285,t3=3.747,t7=2.729,均P＜0.05).术后第1、3、7天R组的INR高于L组(分别t1=5.260,t3=5.035,t7=2.267,均P＜0.05).本组活体肝移植无供体死亡,供体总的并发症发生为53/154(34.42%),R组52/141(36.88%),L组1/13(7.69%),2组比较差异无统计学意义(x2=3.292,P＞0.05).结论 右叶肝供体组(大体积供肝组)与左叶肝供体组相比,供体术后早期肝功能损害更大;供体总体安全性较好,但仍面临着一定的并发症风险.

Abstract：

Objective To investigate the liver function injury and the rate of complications in living liver transplantation donors in different graft type transplantation.Methods Postoperative data of 154 living liver donors satisfying our inclusion criteria were prospectively collected and registered from Jan 2002 to May 2009 in our hospital.We divided the donors into two groups (right-lobe graft, R group and left-lobe graft, L group), and made comparison on the liver function and complications.Results Remnant liver weight in R group were smaller than those in L group (t = 11.418, P ＜ 0.05).the ratio of remnant liver weight to standard liver weight in R group were smaller than those in L group (t = - 5.040, P ＜ 0.05 ) .Peaks of ALT, AST and INR in both groups appeared on the first day after operation, while the peak of TB in R group appeared on the third day after operation.All the index values returned to a normal baseline after reaching its peak.Mean values of TB in R group were higher than those in L group on the 1st, 3rd, 7th day after operation (seperately t1 = 5.285, t3 = 3.747, t7 = 2.729, all P ＜ 0.05).Mean values of INR in R group were higher than those in L group on the 1st, 3rd, 7th day after operation (seperately t1 = 5.260, t3 = 5.035, t7 = 2.267, all P ＜ 0.05).The level of TB in both groups returned to normal range on the 7th postoperative day, while the level of ALT and AST remained twice the upper limits of the normal.There were no deaths; Complications occurred in 53 of 154 donors (34.42% ) , 52/141 (36.88% ) in R group and 1/13 (7.69% ) in L group (x2 = 3.292, P ＞ 0.05).Conclusions Ramnant liver function of R group during early postoperative period was poorer than that of the L group.Donors were safe, though suffering from comparatively high complication rate.     

肝肾联合移植28例临床分析

目的 总结肝肾联合移植治疗终末期肝脏合并肾脏疾病的体会.方法 对28例肝肾联合移植的临床资料进行回顾分析,并对手术适应证的选择、手术方式、免疫制剂方案的应用以及预后情况进行了分析整理和总结.结果 肝肾联合移植各种适应证中,肝肾功能衰竭占78.6 %(22/28),肝肾综合征占14.3 %(4/28),高草酸盐尿症及多囊肾合并多囊肝各占3.6 %(各1/28).所有受者均先行肝移植,再行肾移植.肝移植采用背驮式者4例,采用经典非转流式者24例,供肾植入位置首选右侧髂窝.术后随访5个月至7年8个月,受者1年存活率为92.9 %(26/28),3年存活率为78.3 %(18/23).28例受者中,围手术期发生移植肾功能不良4例,其中3例经保守治疗病情好转,1例死亡.1例因移植肝并发症于术后3个月再次行肝移植治疗,后好转,期间肾功能未受影响.术后发生肺部感染11例,其中1例死亡,其余10例经治疗后痊愈.无一例发生急性排斥反应.结论 肝肾联合移植是治疗终末期肝脏合并肾脏疾病的有效手段,术前应严格控制手术适应证,把握适当的手术时机.

Abstract：

Objective To summarize the experience of treating the end stage of liver disease complicated with renal failure using combined liver-kidney transplantation.Methods The clinical data of 28 cases receiving combined liver-kidney transplantation were retrospectively analyzed, including the inclusion criteria of surgical indications, modus operandi, protocol of immunosuppression and the prognosis post-operation.Results Among these 28 cases in our study, 22 cases suffered from liver and renal failure, accounting for 78.6%; 4 cases were diagnosed as having hepatorenal syndrome, accounting for 14.3%; and 1 case had hyperoxaluria and polycystic liver with polycystic kidney. As for the modus operandi we used, piggy-back procedure was adopted for 4 patients and classic procedure without bypass was used for the rest. Donor kidneys were all put in the right iliac fossa. During the follow-up period of 5 months to 7 years, one-and 3-year survival rate of the recipients was 92.9% and 78.3% respectively. Among these 28 recipients, 4 cases had the graft renal dysfunction early post-operation: One died and 3 recovered through consecutive therapy. One case received re-transplantation of the liver 3 months after the first due to the relevant complications and then recovered. During this period, no impact on the renal function occurred. Eleven cases had pulmonary infection post-operation, and 1 died. No acute rejection occurred.Conclusion Combined liver-kidney transplantation is the effective treatment to the patients with end stage liver disease complicated with renal dysfunction. Suitable case selection and perfect operation timing were the key points to the success of combined liver-kidney transplantation.     

胃旁路术治疗2型糖尿病的作用机制

目的 探讨胃旁路术治疗2型糖尿病大鼠的作用机制.方法 将72只8周龄的GK大鼠按照随机数字表法分为手术组、假手术组、饮食控制组和对照组,每组18只.手术组大鼠施行胃旁路术,假手术组大鼠施行离断胃窦十二指肠原位吻合术,饮食控制组大鼠按15 g/d控制每只大鼠进食量,对照组大鼠自由进食.术前、术后第2、4、8周检测各组大鼠空腹、餐后血糖和胰高血糖素样肽-1(GLP-1).术后第2、4、8周检测各组大鼠餐后血糖和GLP-1后处死大鼠(每组6只),取出胰腺组织采用TUNEL法检测胰岛β细胞凋亡情况.采用t检验分析数据.结果 手术组大鼠术前空腹和餐后血糖分别为(16.2±0.8)mmol/L和(31.1±1.1)mmol/L,术后第4、8周逐渐降低为(9.2±0.6)mmol/L和(13.1±0.7)mmol/L、(9.7±0.7)mmol/L和(12.3±0.7)mmol/L,手术前后比较,差异有统计学意义(t=20.7、49.7,18.8、39.0,P<0.05).手术组大鼠术后第4、8周空腹和餐后血糖水平明显低于同时相点的假手术组、饮食控制组和对照组(t=27.7、-57.8,11.3、-59.9,-27.4、-48.2,-13.2、-52.7,-7.0、-24.9,-18.2、-56.4,P<0.05).手术组大鼠术前空腹和餐后GLP-1分别为(10.7±1.0)pmol/L和(42.5±1.2)pmol/L,术后第4、8周逐渐升高为(26.1±0.9)pmol/L和(90.7±1.7)pmol/L、(25.3±1.2)pmol/L和(90.4±2.0)pmol/L,手术前后比较,差异有统计学意义(t=-42.1、-92.4,-29.1、-72.7,P<0.05).手术组大鼠术后第4、8周空腹和餐后GLP-1水平明显高于同时相点的假手术组、饮食控制组和对照组(t=48.0、61.9,38.0、62.2,50.9、65.2,37.0、48.1,27.5、51.6,17.5,52.9,P<0.05).手术组大鼠胰岛随着术后时间的延长,凋亡细胞数逐渐减少,细胞凋亡率明显降低.手术组、假手术组、饮食控制组和对照组术后第4、8周细胞凋亡率分别为5.9%±0.7%、47.2%±1.0%、21.1%±1.2%、46.5%±1.4%和6.3%±1.1%、47.2%±1.0%、21.2%±1.2%、46.0%±1.4%,手术组细胞凋亡率较同时相点的假手术组、饮食控制组、对照组明显降低(t=-82.2、-67.0,-27.1、-22.4,-55.2、-54.6,P<0.05).结论 胃旁路手术后2型糖尿病大鼠血糖降低,GLP-1分泌明显增加,可以显著抑制胰岛β细胞凋亡.

Abstract：

Objective To investigate the mechanism of gastric bypass surgery in the treatment of type 2 diabetes mellitus in a rat model. Methods Seventy-two 8-week-old GK rats were randomly divided into operation group, sham operation group, diet control group and control group (18 rats in each group) according to the random number table. Rats in the operation group and the sham operation group received gastric bypass surgery and transection and reanastomosis of the gastrointestinal tract, respectively. The food intake was set as 15 g/d for each rat in the diet control group, while rats in the control group were fed ad libitum. The levels of fasting blood glucose ( FBG), postprandial blood glucose (PPBG) and glucagon-like peptide-1 (GLP-1) were detected before operation and at postoperative week 2, 4 and 8. The levels of PPBG and GLP-1 were detected at postoperative week 2, 4 and 8, then 6 rats of each group were sacrificed to detect the apoptosis of islet B cells using the TUNEL method. All data were analyzed using the t test. Results In the operation group, the preoperative levels of FBG and PPBG were (16.2±0.8)mmol/L and (31.1 ± 1. L)mmol/L, respectively, which were significantly higher than (9.2± 0.6) mmol/L and (13.1 ±0.7) mmol/L at 4 weeks after the operation, and (9. 7 ± 0. 7) mmol/L and (12. 3 ± 0.7) mmol/L at 8 weeks after the operation (t = 20. 7, 49. 7; 18. 8, 39. 0, P < 0.05 ). The levels of FBG and PPBG before the operation and at 4 and 8 weeks after the operation in the operation group were significantly lower than those in the sham operation group, diet control group and control group at corresponding time points (t = 27.7, -57.8; 11.3, -59.9; -27.4, -48.2; -13.2, -52.7; -7.0, -24.9; -18.2, -56.4, P<0.05). In the operation group, the levels of fasting GLP-1 and postprandial GLP-1 were ( 10. 7 ± 1. 0) pmol/L and (42.5 ±1.2)pmol/L, respectively, which were significantly lower than (26. 1 ±0.9)pmol/L and (90.7 ± 1.7)pmol/L at4 weeks after the operation, and (25.3 ± 1.2)pmol/L and (90.4 ±2.0)pmol/L at 8 weeks after the operation (t=42.1, -92.4; -29.1, -72.7, P <0.05). The levels of fasting GLP-1 and postprandial GLP-1 before the operation and at 4 and 8 weeks after the peration in the operation group were significantly higher than those in the sham operation group, diet control group and control group at corresponding time points (t = 48.0, 61.9; 38.0, 62.2; 50.9, 65.2; 37.0, 48. 1; 27.5, 51.6; 17.5, 52.9, P<0.05). The number of the apoptotic islet β cells in the operation group was decreased with time. The apoptosis rates in the operation group, sham operation group, diet control group and control group were 5.9%±0.7% , 47.2%± 1.0% , 21. 1%± 1. 2% , 46.5%±1.4% at 4 weeks after the operation, and 6.3%±1. 1% , 47.2%±1.0% , 21.2%±1.2% and 46.0% ± 1.4% at 8 weeks after the operation. The apoptosis rates in the operation group were significantly lower than those in the sham operation group, diet control group and control group at corresponding time points (t = -82. 2, - 67. 0; - 27. 1, - 22. 4; - 55. 2, - 54. 6, P < 0.05). Conclusion After gastric bypass surgery, the level of blood glucose reduces and the level of GLP-1 increases which significantly inhibit the apoptosis of islet B cells in rats with type 2 diabetes mellitus.     

影响肝移植术后新发糖尿病逆转的相关因素

目的 探讨影响肝移植术后新发糖尿病(PTDM)逆转的相关因素.方法 回顾分析232例肝移植受者的临床资料,术后共有62例患者发生PTDM,发生率为26.7%.根据PTDM是否发生逆转,将62例患者分为暂时性PTDM组(34例)和持续性PTDM组(28例).对两组患者的性别、年龄、体重指数、糖尿病家族史、乙型肝炎病毒感染情况、术前空腹血糖水平、免疫抑制剂使用及其血药浓度、皮质激素的使用时间等相关因素进行分析.结果 两组间患者的性别、体重指数、糖尿病家族史、术前空腹血糖水平、免疫抑制方案中皮质激素的持续使用时间、术后血他克莫司浓度及使用环孢素A的患者比例等因素的差异均无统计学意义(P＞0.05).与持续性PTDM组相比,暂时性PTDM组患者移植时年龄较轻,分别为(54±8)岁和(42±6)岁(P＜0.05);发生PTDM的术后时间较晚,分别为术后(18±23)d和(35±42)d(P＜0.05);免疫抑制方案中联合运用吗替麦考酚酯(MMF)或西罗莫司(SRL)的患者比例较高,分别为0和8.9%(P＜0.05).经多因素Logistic回归分析显示,只有移植时年龄是PTDM逆转的独立预测因子(比值比为1.312,95%可信区间为1.005～1.743).结论 患者移植时年龄、发生PTDM时的术后时间及免疫抑制方案中使用MMF或SRL的患者比例等因素与肝移植术后PTDM逆转相关,但只有移植时年龄是PTDM逆转的独立预测因子.

Abstract：

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.     

输注转染人IL-10基因的骨髓间充质干细胞减轻大鼠异种移植肝脏的细胞凋亡

Objective To observe the influence of hIL-10-MSCs on apoptosis of rats subject to discordant liver xenotransplantation. Methods The model of guinea pig to rat discordant liver xenotransplantation was set up. The orthotopic liver transplantation model was established by using modified two-cuff technique. Following groups were designed: control group, MSCs group and hIL-10MSCs group. Before and after operation, the recipients in control group were injected with normal sodium (2 ml) and decaesadril (0.5 ml) ;Those in MSCs group were injected with MSCs (4.0× 106/ml)and decaesadril (0.5 ml); Those in hIL-10-MSCs group were injected with hIL-10-MSCs (4.0 × 106/ ml)and decaesadril (0.5 ml). Twelve h after operation, the livers of recipient were observed by HE staining and electron microscope, and apoptosis of the livers was detected by using TUNEL. The expression levels of hIL-10, caspase-3, Fas and FasL were assayed by Western blot or immunohistochemistry. Results As compared with control group and MSCs group, the pathological changes was alleviated, the expression of IL-10 was significantly increased, the expression of FasL was significantly reduced in hIL-10-MSCs group. The positive area size of Fas and Caspase-3 in hIL-10MSCs group was 11.5 % and 25.1 %, respectively, significantly smaller than those in control group (35.3 % and 70.8 % respectively, P＜0.05. Apoptosis index in hIL-10-MSCs group was 32.5 %,which was significantly lower than in control group (74.1%) and MSCs group (50. 3 % ). ConclusionhIL-10-MSCs can notably decrease apoptosis of the transplanted liver probably by inhibiting theexpression of Fas/FasL.     

血清前白蛋白检测评价肝功能损害的临床应用

目的 探讨血清前白蛋白浓度测定在临床肝功能损害评价中的价值.方法 分析80例接受脾切除+贲门周围血管离断术的肝硬化患者术前血清前白蛋白(PA)水平、终末期肝病模型(MELD)与术后出现肝功能衰竭的关系.结果 术后出现肝功能衰竭的患者术前的PA值为(79.8±28.5)mg/L,较术后未出现肝功能衰竭情况患者的术前PA值(149.6±31.5)mg/L明显降低(P＜0.01).单独使用MELD评分≥9分和PA值＜100mg/L来判断肝硬化门脉高压患者术后是否出现肝功能衰竭的敏感性分别为71.4%和69.6%,使用MELD评分联合PA值来判断术后是否出现肝功能衰竭的敏感性为82.4%,明显高于单独使用MELD和PA值(P＜0.01).单独使用MELD评分≥9分、PA值＜100 mg/L和MELD评分联合PA值三种方法对术后肝功能衰竭情况评价的特异性都较强,分别为93%、91.5%和90.5%,但三种方法之间的差异无统计学意义(P＞0.05).结论 前白蛋白可反映乙肝后肝硬化门脉高压患者的肝功能损害程度.术前MELD评分联合PA值评估术后是否出现肝功能衰竭情况有良好的敏感性及特异性,可应用于临床.

Abstract：

Objective To investigate the clinical use of serum prealbumin (PA) in evaluating liver function damage. Methods Preoperative PA and the model for end-stage liver disease (MELD) score were retrospectively analyzed in 80 patients with liver cirrhosis and portal hypertension undergoing splenectomy and devascularization around the cardia. The correlation of preoperative PA level and MELD score with postoperative hepatic failure was also analyzed. Results The mean serum value of PA in the patients with hepatic failure was (79. 8 ± 28.5 ) mg/L, and that in thouse without hepatic failure was ( 149. 6 ±31.5 ) mg/L ( P ＜ 0. 01 ). The sensitivity of using MELD score ≥9 to evaluate postoperative hepatic failure was 71.4%, that of PA ＜ 100 mg/L was 69. 6%, and that of MELD score ≥9 combined with PA ＜ 100mg/L was 82. 4% respectively (P ＜0. 01 ). The specificity of the three methods was 93%, 91.5% and 90. 5% respectively, with the difference being not significant (P ＞ 0. 05). Conclusion The serum level of PA could reflect the liver function damage sensitively and exactly. Preoperative MELD score combined with serum PA has good sensitivity and specificity in predicting postoperative hepatic failure and could be used clinically.     

Notch2基因在大鼠肝移植术后胆管损伤中的表达及其意义

目的 探讨大鼠肝移植术后损伤胆管中Notch 2基因的表达及其意义.方法 将96只健康雄性SD大鼠随机分为3组,A组:未手术组;B组:假手术组;C组:采用改良"二袖套"法建立大鼠肝移植.于术后1、7、14、28 d检测总胆红素(TBIL)、γ-GT、谷丙转氨酶(ALT),同时处死大鼠取肝组织,苏木素-伊红(HE)染色观察病理改变,免疫组织化学、Western blot检测Notch 2基因的表达.结果 大鼠肝移植术后TBIL(32.05±3.28)μmol/L,γ-GT(118.30±17.40)μmol/L明显升高(P＜0.05),HE染色显示损伤胆管增生(14 d),部分胆管破坏、消失(28 d).免疫组织化学显示,A和B组胆管细胞Notch 2染色阴性,C组胆管细胞Notch 2染色强阳性,Western blot检测显示Notch 2蛋白在C组肝组织中呈逐渐升高的强表达(P＜0.05).结论 大鼠肝移植术后随胆管损伤加重,Notch 2基因表达显著升高,该基因可能参与了胆管损伤.

Abstract：

Objective To investigate the expression and clinical significance of Notch 2 expression in postoperative injured bile duct of rat liver transplantation. Methods Ninety-six healthy male SD rats were divided into three groups randomly: un-operation group (A), Sham operation group ( B), and group of liver transplantation model by modified "two-muff" techniques (C). Total bilirubin (TBIL), γ-GT and alanine aminotransferase (ALT) were determined at 1st, 7th, 14th, 28th day after transplantation and the expression of Notch 2 in the liver was detected by immunohistochemisty and Western blotting at the same time. Results TBIL (32. 05 ±3. 28) μmol/L, and γ-GT ( 118.30 ± 17.40) μmol/L were increased obviously after liver transplantation ( P ＜ 0. 05 ). Hematoxylin-eosin ( HE ) staining showed the injured bile ducts obviously proliferated after 14 days, and partly posttransplanted bile ducts were destructed and vanished after 28 days. Immunohistochemisty revealed that Notch 2 staining in bile ducts was negative in groups A and B, but Notch 2 staining in hyperplasitic bile ducts was strong positive in group C. Western blotting confirmed that Notch 2 protein was upregulated gradually in the damaged bile ducts after rat liver transplantation (P ＜ 0. 05 ). Conclusion Bile duct injury is aggravated after rat liver transplantation, and Notch 2 gene expression is up-regulated remarkably.     

挽救性肝移植治疗肝癌切除术后肿瘤复发

目的 分析挽救性肝移植治疗肝癌切除术后肿瘤复发患者的疗效.方法 2004年1月至2008年12月,单中心376例肝癌患者接受了肝移植,其中36例(9.6 %)为行根治性肿瘤切除术后因肿瘤肝内复发而接受挽救性肝移植者(挽救性肝移植组).挽救性肝移植组中男性29例,女性7例;16例接受右半肝切除,10例接受左半肝切除,其余10例接受不规则肝切除或肝段切除.首次肝切除至行挽救性肝移植的时间为(34.9±16.2)个月(1～63个月).以同期符合米兰标准并接受首次肝移植的147例作为对照组,比较两组受者的术中情况及术后生存情况、肿瘤复发情况等.结果 挽救性移植组术中出血量和输血量明显多于对照组(P＜0.05),手术时间也长于对照组(P＜0.05).随访期间,挽救性肝移植组死亡11例,其中围手术期死亡1例;对照组共死亡36例,其中围手术期死亡3例.两组手术后并发症、肿瘤复发率、受者存活率以及无瘤存活率的差异无统计学意义(P＞0.05).结论 挽救性肝移植虽然较首次肝移植手术难度增加,但不影响患者预后,是根治性肝癌切除术后肿瘤复发患者的有效治疗手段.

Abstract：

Objective To summarize the experience with salvage liver transplantation for patients with recurrent hetaptocellular carcinoma(HCC)after primary liver resection.Methods From 2004 to 2008,376 patients with HCC received liver transplantation in our single center.Among these patients,36 (9.6 %)underwent salvage liver transplantation after primary liver curative resection due to intrahepatic recurrence.There were 29 males and 7 females with the mean age of 46 years old.Sixteen received right lobectomy,10 received left lobectomy and the others received sectionectomy or segmentectomy.As a control group for comparison,we used clinical data of the 147 patients who underwent primary OLT for HCC within Milan Criteria.Results The mean interval between initial liver resection and salvage transplantation was 34.9±16.2 months(1-63 months).Intraoperative bleeding volume,transfusion volume and operative time in the salvage group were significantly different from those in control group (P<0.05).There were no significant difference in post-operative complications,tumor recurrence rate,survival rate and tumor-free survival between these two groups(P>0.05).Conclusion In comparison with primary OLT,although salvage liver transplantation would increase the operation difficulties,it still remains a good option for patients with HCC recurrence after curative resection.     

Renal Recovery After Liver Transplantation Alone in Patients With Liver Cirrhosis and Severe Chronic Kidney Disease With Normal Kidney Size

BackgroundMost guidelines recommend simultaneous liver-kidney transplantation (SLKT) in patients with liver cirrhosis (LC) and severe chronic kidney disease (CKD) over liver transplantation alone (LTA). CKD, however, is not irreversible. This study evaluates the reversibility of kidney disease after LTA based on kidney size.Materials and methodsIn this single-center retrospective study, we classified 90 patients with LC and severe CKD into 3 groups: the normal kidney (NK)-LTA group (n=39), small kidney (SK)-LTA group (both kidneys <9 cm at the time of LTA, n=40), and SK-SLKT group (n=11).ResultsThe NK-LTA group had a lower percentage of hepatocellular carcinoma and a higher pre-liver transplantation (LT) estimated glomerular filtration rate. This group, however, was older, received livers from a higher percentage of deceased donors, and had a higher Child-Pugh score. Renal recovery, defined as the return of creatinine to their baseline, or a persistent change from baseline but not persistent (≥3 months) need for renal replacement therapy after LT, was found in 79% in the NK-LTA group, which was higher than 7.5% in the SK-LTA group. Renal and patient survival was found in 56% of the NK-LTA group, which was higher than 2.5% of the SK-LTA group.ConclusionsThere is a high percentage of renal recovery in the NK-LTA group, and accordingly, this does not justify SLKT, since this would result in a "waste" of kidneys. Therefore, KT after LT is recommended over SLKT for the LC patients with NK size.     

Isolated acute cellular rejection of the liver after simultaneous liver and kidney transplantation: a case report

Simultaneous liver and kidney transplantation (SLKT) is now considered the treatment of choice for patients with concurrent end-stage liver and kidney diseases. Even though the early postoperative mortality rate following SLKT is reported to be high compared to that of liver transplantation alone, the liver graft from the same donor has been argued to induce better kidney graft acceptance as evidenced by a low rate of acute renal rejection episodes. There have been many reports of a low incidence of acute renal rejection following SLKT; however, only a few cases were proven by simultaneous biopsies. The authors experienced a case of biopsy-proven isolated acute cellular rejection of the liver graft following SLKT.     

Liver,simultaneous liver-kidney,and kidney transplantation from hepatitis C-positive donors in hepatitis C-negative recipients: A single-center study

Transplantation of organs from hepatitis C virus (HCV)-antibody (Ab) and -nucleic acid test (NAT) positive donors into HCV-negative recipients has been proposed to expand the donor pool and shorten waiting times. Data on early single-center outcomes are lacking. Nineteen liver (LT, including seven simultaneous liver-kidney [SLKT]) and 17 kidney transplant (KT) recipients received organs from HCV (+) donors; of these, 13 were HCV NAT (+) in each group. All patients who received organs from HCV NAT (+) donors developed HCV viremia post-transplant except for 2 KT recipients. Patients were treated with a variety of direct-acting antiviral regimens, with high rates of sustained virologic response among those with at least 12 weeks of follow-up past the end of treatment: 12/13 (92%) and 8/8 (100%) among LT/SLKT, and KT recipients. Median time to treatment start was 42 days (interquartile range [IQR] 35-118 days) and 40 days (IQR 26-73) post-LT/SLKT and KT, respectively. One death occurred in a SLKT recipient unrelated to HCV or its treatment. There was no significant increase in rejection, proteinuria, or changes in immunosuppression in any group. Organs from HCV-viremic donors can be utilized for HCV-uninfected recipients with good short-term outcomes.     

Simultaneous liver-kidney versus liver transplantation alone in patients with end-stage liver disease and kidney dysfunction not on dialysis

Background

Since implementation of the Model for End-stage Liver Disease (MELD), the number of simultaneous liver-kidney transplantations (SLKT) has increased in the United States. However, predictors and survival benefit of SLKT compared to liver transplantation alone (LTA) are not well defined.

Methods

Organ Procurement and Transplantation Network data of patients with end-stage liver disease (ESLD) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² who had not been on dialysis while on the waiting list and underwent liver transplantation between 2002 and 2008 were analyzed. To identify predictors of undergoing SLKT versus LTA, multiple logistic regression analysis was performed. Cox proportional hazards regression analysis was used to assess the association between SLKT and post–liver transplant patient and graft survival.

Results

The study cohort comprised 5443 patients; 262 (5%) underwent SLKT and 5181 (95%) underwent LTA. Adjusting for potential confounders, patients who underwent SLKT were 34% less likely to die after liver transplantation than those who underwent LTA (hazard ratio [HR] = 0.66, P = .012) and 33% less likely to have liver graft failure than those who underwent LTA (HR = 0.67, P = .010). Among those who underwent SLKT, 1-, 3-, and 5-year kidney graft survival probabilities were 88%, 80%, and 77%, respectively. Black race and diabetes were associated with a higher likelihood of SLKT versus LTA; female sex, a higher eGFR, and higher MELD score reduced the likelihood of SLKT.

Conclusions

Among those with ESLD and kidney dysfunction not on dialysis, post–liver transplant patient and liver graft survivals of patients who underwent SLKT were superior to those of patients who underwent LTA. Whether this reflects differences in the two groups that could not be adjusted in survival models or a specific effect of kidney dysfunction cannot be established.     

Renal transplantation in end-stage sickle cell nephropathy

BACKGROUND: The role of renal transplantation as treatment for end-stage sickle cell nephropathy (SCN) has not been well established. METHODS: We performed a comparative investigation of patient and allograft outcomes among age-matched African-American kidney transplant recipients with ESRD as a result of SCN (n=82) and all other causes (Other-ESRD, n=22,565). RESULTS: The incidence of delayed graft function and predischarge acute rejection in SCN group (24% and 26%) was similar to that observed in the Other-ESRD group (29% and 27%). The mean discharge serum creatinine (SCr) was 2.7 (+/-2.5) mg/dl in the SCN recipients compared to 3.0 (+/-2.5) mg/dl in the Other-ESRD recipients (P=0.42). There was no difference in the 1-year cadaveric graft survival (SCN: 78% vs. Other-ESRD: 77%), and the multivariable adjusted 1-year risk of graft loss indicated no significant effect of SCN (relative risk [RR]=1.39, P=0.149). However, the 3-year cadaveric graft survival tended to be lower in the SCN group (48% vs. 60%, P=0.055) and their adjusted 3-year risk of graft loss was significantly greater (RR= 1.60, P=0.003). There was a trend toward improved survival in the SCN transplant recipients compared to their dialysis-treated, wait-listed counterparts (RR=0.14, P=0.056). In comparison to the Other-ESRD (RR=1.00), the adjusted mortality risk in the SCN group was higher both at 1 year (RR=2.95, P=0.001) and at 3 years (RR=2.82, P=0.0001) after renal transplantation. CONCLUSIONS: The short-term renal allograft result in recipients with end-stage SCN was similar to that obtained in other causes of ESRD, but the long-term outcome was comparatively diminished. There was a trend toward better patient survival with renal transplantation relative to dialysis in end-stage SCN.     

他克莫司与环孢素A在高致敏肾移植受者中的应用比较

目的 观察和比较高致敏肾移植受者应用他克莫司(FK506)与环孢素A(CsA)的有效性和安全性.方法 根据术后免疫抑制方案的不同,将147例高致敏肾移植受者(其中术前群体反应性抗体＞50%的首次肾移植受者59例,2次肾移植受者88例)分为FK506组(53例)和CsA组(94例),两组的免疫抑制方案分别为FK506(或CsA)+霉酚酸酯+泼尼松.观察并分析两组受者术后移植肾存活率、血肌酐水平以及并发症的发生率.结果 FK506组术后1、3和5年的移植肾存活率(86.8%、82.3%和75.3%)略高于CsA组(81.9%、75.4%和66.9%),但差异无统计学意义(P＞0.05);FK506组术后1年时血肌酐水平为(100.72±15.88)μmol/L,CsA组为(117.29±11.77)μmol/L,两组比较,差异有统计学意义(P＜0.01);FK506组与CsA组相比,术后急性排斥反应、慢性排斥反应、肝功能损害、高血压和高血脂的发生率显著降低(P＜0.05),而高血糖的发生率明显升高(P＜0.01),两组移植肾功能延迟恢复和感染的发生率无明显差异(P＞0.05).结论 FK506与CsA相比,能有效降低高致敏受者肾移植术后急、慢性排斥反应的发生率,减少术后并发症的发生,提高移植肾的长期存活率,对高致敏肾移植受者是非常有效和安全的.     

Outcome of living kidney transplant: pediatric in comparison to adults

BACKGROUND: Renal transplantation is the most optimal way to manage children with end-stage renal disease. Despite its benefits, pediatric renal transplantation is a challenge for several transplantation centers in terms of achieving a satisfactory outcome. We sought to compare the long-term outcome of pediatric versus adult recipients who underwent renal transplantation. METHOD: We examined, 2631 recipients of a first kidney from a living donor between 1982 and 2002. The two groups were matched for immunosuppressive therapy and number of HLA mismatches. The patients were divided into a pediatric (n=301; age 18 years) to compare 5-year patient and graft survivals. RESULTS: The mean ages of the pediatric and adult groups were 40 +/- 13 and 14 +/- 13 years, respectively. The 5-year graft survival was lower among the pediatric versus the adult group (56% vs 68%; P=.015) with no difference in patient survival (88% vs 86%; P>.05). CONCLUSION: The poorer graft survival in pediatric transplantation may be due to the nature of pediatric transplantation, in terms of inconsistent adherence to medication regimens, worse side effects of medications, higher rate of graft rejection due to recurrent disease, and more intense immunoreactivity of children.     

Class II Alloantibody and Mortality in Simultaneous Liver‐Kidney Transplantation

Hyperacute kidney rejection is unusual in crossmatch positive recipients of simultaneous liver–kidney transplants (SLKT). However, recent data suggest that these patients remain at risk for antibody‐mediated kidney rejection. To further investigate the risk associated with donor‐specific alloantibodies (DSA) in SLKT, we studied 86 consecutive SLKT patients with an available pre‐SLKT serum sample. Serum samples were analyzed in a blinded fashion for HLA DSA using single antigen beads (median florescence intensity ≥ 2,000 = positive). Post‐SLKT samples were analyzed when available (76%). Thirty patients had preformed DSA, and nine developed de novo DSA. Preformed class I DSA did not change the risk of rejection, patient or allograft survival. In contrast, preformed class II DSA was associated with a markedly increased risk of renal antibody mediated rejection (AMR) (p = 0.006), liver allograft rejection (p = 0.002), patient death (p = 0.02), liver allograft loss (p = 0.02) and renal allograft loss (p = 0.045). Multivariable modeling showed class II DSA (preformed or de novo) to be an independent predictor of patient death (HR = 2.2; p = 0.043) and liver allograft loss (HR = 2.2; p = 0.044). These data warrant reconsideration of the approach to DSA in SLKT.     

Liver Transplant Recipients With End-Stage Renal Disease Largely Benefit From Kidney Transplantation

Background

The incidence of end-stage renal disease (ESRD) after liver transplant (LT) has increased. The actual benefit of kidney transplantation (KT) is not completely understood in LT recipients with ESRD.

Outcomes of pediatric ABO-incompatible kidney transplantations are equivalent to ABO-compatible controls

Background

Due to the profound shortage of suitable deceased allografts, much effort has been made to investigate whether successful kidney transplantation (KT) is possible across the ABO blood group barrier even for pediatric recipients.

Methods

We reviewed 52 consecutive ABO incompatible (ABOic) transplantation performed between September 1989 and March 2011. The mean age at transplantation was 10.6 ± 3.9 years (range, 4.4-19.7), with 35 boys and 17 girls. The donor-to-recipient ABO blood antigen incompatibility was as follows: A1/O (n = 17); B/O (n = 13); A1/B (n = 6); B/A1 (n = 1); A1B/B (n = 9); and A1B/A (n = 6). As a control group, data were collected from 271 pediatric ABO compatible (ABOc) living donor KT in the same period.

Results

Overall acute rejection episodes (ARE) among the ABOic group were significantly higher than those of the ABOc group (44% vs 26%; P < .02). However, there was no difference in glomerular filtration rate (GFR) at 1 year after transplantation: 86 ± 31 mL/min for ABOic vs 99 ± 37 mL/min for ABOic, respectively.The 1-y, 5-y, and 10-year patient survival rates were 98%, 92%, and 92% in the ABOic group, respectively, and 99%, 98%, and 97% in the ABOc group, respectively (P = not significant [NS]). The overall 1-, 5-, 10-, and 15-year graft survival rates were 94%, 88%, 86%, and 86% in the ABOic group, respectively, and 95%, 92%, 88%, and 78% in the ABOc group, respectively.

Conclusion

ABOic KT provided long-term allograft and patient survivals equivalent to ABOc live donor transplantations.