采用他克莫司和霉酚酸酯并辅以两剂达利珠单抗的无激素免疫抑制方案预防肝移植后急性排斥反应

目前，大多数移植中心采用包括激素在内的免疫抑制方案预防器官移植后的急性排斥反应，然而长期的激素治疗会带来一系列代谢方面的紊乱以及心血管等方面的并发症，如糖尿病、高血压、高血脂等，而且使感染的机会增多。我们尝试在肝移植后使用他克莫司（FK506）和霉酚酸酯（MMF），并辅以两剂达利珠单抗的无激素免疫抑制方案，现报告如下。     

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.     

肝硬化或肝癌伴银屑病患者肝移植术后治疗经验

目的总结患有银屑病的肝移植受者免疫抑制治疗的临床经验。方法以5例肝硬化或肝细胞癌(肝癌)伴银屑病的肝移植受者为研究对象,其乙型肝炎病毒(HBV)血清标志物均阳性。术前采用诱导方案,术后早期采用他克莫司(FK506)+吗替麦考酚酯(MMF)+肾上腺皮质激素(激素)三联免疫抑制方案,1周内停用激素。3例乙型病毒性肝炎(乙肝)后肝硬化合并肝癌肝移植患者1个月内逐步转换为西罗莫司替代治疗;2例乙肝后肝硬化肝移植受者患者一直采用FK506加或不加MMF方案。全部患者均予抗HBV治疗。分析其基本情况、银屑病皮损面积和严重性指数(PASI)评分变化及术后免疫抑制剂治疗方案的调整情况。结果 5例患者肝移植术后至投稿日随访(8.3±1.5)年,均存活。与术前相比,患者术后6个月PASI评分明显降低(P0.05)。2例乙肝后肝硬化肝移植受者患者在术后2年后出现银屑病复发,PASI评分显著升高,改为西罗莫司替代FK506的治疗方案后逐步下降,术后3年开始维持在稳定状态,无进展;3例乙肝后肝硬化合并肝癌肝移植受者无复发。结论以西罗莫司为主的免疫抑制治疗方案可有效控制肝移植受者的银屑病病情,对HBV阳性患者应同时进行抗HBV治疗。     

肝移植术后应用不含皮质激素的免疫抑制方案对糖代谢的影响

目的 探讨肝移植术后应用不含皮质激素的免疫抑制方案对受者糖代谢的影响.方法 回顾分析295例首次接受成人肝移植,且术后规律随访超过6个月受者的临床资料,将受者分研究组(153例)和对照组(142例),研究组受者采用他克莫司(Tac)+吗替麦考酚酯( MMF)的免疫抑制方案,对照组受者采用Tac+ MMF+皮质激素方案.分别于术前1周及术后第1、2、4、8、12、16、20和24周为观察时间点,检测两组受者的血糖水平变化,观察急性排斥反应及高血糖相关不良事件的发生情况.结果 两组间受者性别、年龄、体重等基本资料,尤其是术前空腹血糖水平和高血糖患者比例的差异均无统计学意义(P＞0.05).两组受者术后早期血糖水平均显著升高,术后1周时达到峰值,并随术后时间的延长呈逐渐下降的趋势.各时间点研究组的受者李腹血糖水平及高血糖患者比例均低于对照组,术后4周以后,与对照组比较,差异均有统计学意义(P＜0.05).研究组和对照组高血糖者的比例分别为52.9％和76.8％(P＜0.05),对照组术后发生高血糖的风险是研究组的2.94倍.随访期间,研究组和对照组的急性排斥反应发生率分别为8.50％ (13/153)和7.75％(11/142),两组比较,差异无统计学意义(P＞0.05).研究组受者出现组织愈合延迟、感染及高脂血症发生率亦低于对照组.结论 肝移植术后应用不含皮质激素的免疫抑制方案是安全的,并可降低术后发生糖尿病的风险,减少高血糖相关不良事件的发生率.     

肝移植后应用巴利昔单抗同时撤减激素的免疫抑制治疗方案

目的 探讨肝移植后加用巴利昔单抗的情况下采用撤减激素的免疫抑制方案的临床效果.方法 首次肝移植患者60例,术后采用他克莫司和霉酚酸酯预防排斥反应,并分别于术中和术后第4天各给予1剂巴利昔单抗,其中20例不用激素,40例仅术中开放血流前使用甲泼尼龙1次,术后不再使用激素,此60例为撤减激素组.以同期完成的、术后采用含甲泼尼龙的免疫抑制方案的60例肝移植患者为对照组.观察两组患者及移植物的存活情况以及急性排斥反应、巨细胞病毒磷蛋白(CMV pp65)阳性及术后新发糖尿病的发生情况.结果 术后随访12个月,不用激素者、单次使用激素者及对照组的患者存活率分别为95.0%、92.5%和91.7%,移植肝存活率分别为95%、90%和90%,急性排斥反应发生率分别为10.0%、12.5%及11.7%,三者间两两比较,患者存活率、移植肝存活率和急性排斥反应发生率的差异均无统计学意义.不用激素者、单次使用激素者及对照组的CMV pp65阳性率分别为15.0%、20.0%和43.3%,新发糖尿病发生率分别为5.0%、7.5%和30.0%,撤减激素组明显低于对照组(P<0.05).结论 肝移植后,在加用巴利昔单抗的情况下采用撤减激素的免疫抑制方案,并不增加排斥反应的发生率,并能降低CMV pp65阳性率和新发糖尿病发生率.     

肝移植术后长期存活慢性肾功能损害受者的免疫抑制方案个体化应用

目的探讨肝移植术后长期存活慢性肾功能损害受者应用个体化免疫抑制方案的疗效。方法选择18岁以上、肝移植术后2年以上、入组前采用以他克莫司(FK506)为基础免疫抑制方案、肝功能正常而肾功能损害的受者,共32例。根据免疫功能评分和白细胞计数制定个体化免疫抑制方案,以FK06用量最小化为原则,转换为麦考酚吗乙酯(MMF)或西罗莫司,并调整其用量。调整后至少每个月随访1次,进行肝功能、肾功能、血常规检查和免疫功能评估。结果 32例受者经个体化免疫抑制方案治疗,随访(24.3±7.6)个月,个体化治疗后各时段的肾小球滤过率(GFR)均较此前有明显提高(均为P<0.01),以调整用药后1个月最明显。无发生排斥反应。结论根据免疫功能评分和白细胞计数制定个体化免疫方案,使FK506用量最小化,可以有效改善肝移植术后长期存活的受者的肾功能,并不增加排斥反应的发生率。     

两剂激素联合两剂达利珠单抗及他克莫司的免疫抑制方案在肝移植中的应用

目的 探讨两剂激素联合两剂达利珠单抗及他克莫司(FK506)的免疫抑制方案在肝移植中应用的安全性及有效性.方法 中山大学附属第一医院器官移植中心2006年9月至2008年3月共实施成人肝移植74例,排除3例血型不合、4例围手术期死亡外,余67例纳人本研究,其中男性54例,女性13例,年龄28～66岁,平均(46.9±8.7)岁.将67例成人肝移植患者随机分为两组:传统免疫抑制方案(激素3个月撤离)组(n=35)和两剂激素免疫抑制方案组(n=32),比较两组术后代谢并发症、感染(含细菌、真菌及巨细胞病毒感染)及排斥反应的发生率的差异.结果 两组患者的术后早期高血糖发生率,高血糖患者使用胰岛素的平均剂量,随访期内糖尿病、高血压及感染的发生率的差异有统计学意义(P<0.05);术后早期高血压发生率及随访期内排斥反应的发生率和高脂血症发生率无明显差异(P0.05).结论 两剂激素的免疫抑制方案是安全有效的,其不增加急性排斥反应的发生率,并可显著减少长期使用激素引起的各种不良反应及并发症的发生.     

肝肾联合移植1例报告

笔者对1例乙肝后肝硬化（失代偿期）、慢性肾衰竭（尿毒症期）的患者施行一期肝肾联合移植。采用背驮式肝移植及常规肾移植。术后免疫抑制方案采用达利珠单抗（赛尼哌）、他克莫司（FK506）、酶酚酸酯（MMF）及激素联合用药。患者顺利渡过围手术期，移植肝肾功能良好，现已存活15个月。提示完善的手术技术，围手术期合理治疗措施是肝肾联合移植成功的关键;移植肝对肾脏具有保护作用。     

肾移植术后患者应用西罗莫司对他克莫司剂量的影响

目的观察肾移植术后联合应用西罗莫司(雷帕霉素)对他克莫司(FK506)剂量的影响。方法60例肾移植术后患者随机分为两组,研究组30例,免疫抑制方案采用西罗莫司+他克莫司+泼尼松;对照组30例,采用麦考酚吗乙酯(MMF)+他克莫司+泼尼松联合治疗。术后随访2年,比较两组的人、肾存活率,急性排斥反应率,他克莫司用量,肾功能变化和不良事件发生率。结果研究组、对照组全部如期完成观察,两组的人肾存活率均为100%,研究组、对照组急性排斥反应发生率分别为7%(2/30)、10%(3/30),经肾上腺皮质激素(激素)冲击治疗后逆转;研究组在维持他克莫司血药浓度与对照组相当情况下,其用量低于对照组,比较差异有统计学意义(P0.05)。两组的不良事件发生率相近(60%比70%,P0.05)。结论联合西罗莫司+他克莫司+泼尼松方案用作肾移植术后免疫抑制治疗是安全有效的,且能减少他克莫司的剂量。     

无皮质激素的免疫抑制方案对肝移植后近期急性排斥反应发生率的影响

目的 探讨无皮质激素的免疫抑制方案对原位肝移植术后近期急性排斥反应发生率的影响.方法 采用随机数字表法将186例肝移植受者分为两组.无皮质激素组(研究组)术后均采用他克莫司(Tac)[或环孢素A(CsA)]+吗替麦考酚酯(MMF)的免疫抑制方案,未使用皮质激素;有皮质激素组(对照组)术后均采用Tac(或CsA)+MMF+皮质激素的三联免疫抑制方案.观察术后6个月内两组间急性排斥反应发生率的差异.急性排斥反应的诊断参照Banff标准.结果 两组受者间性别、年龄、原发病、Child-Pugh评分、终末期肝病模型(MELD)评分、手术时间、术中出血量、输注红细胞悬液及供肝热、冷缺血时间等基本资料的比较,差异均无统计学意义(P＞0.05).观察期内,研究组和对照组接受移植肝穿刺活检各9例次,诊断为急性排斥反应者分别为5和4例,发生率分别为5.3％ (5/94)和4.4％(4/92),两组间比较,差异有统计学意义(P＜0.05).结论 肝移植术后采用无皮质激素的免疫抑制方案不会增加近期(半年内)急性排斥反应的发生率.     

阿来佐单抗行肾移植免疫诱导治疗的有效性和安全性

目的 评价阿来佐单抗行肾移植免疫诱导治疗的有效性和安全性.方法 将89例肾移植受者随机分为试验组(43例)和对照组(46例).试验组于肾移植术前和术后24 h内分别静脉滴注阿来佐单抗15 mg,对照组不接受免疫诱导治疗.受者术后常规应用环孢素A(或他克莫司)+吗替麦考酚酯+泼尼松预防排斥反应.统计两组术后12月内的移植肾功能、急性排斥反应发生率、感染发生率、移植肾功能延迟恢复发生率、移植肾存活率及淋巴细胞计数,并用ImmuKnowTM免疫细胞功能测定法检测受者CD4+T淋巴细胞的三磷酸腺苷(ATP)值.结果 术后12个月内试验组7.0%(3/43)的受者发生病理证实的急性排斥反应,明显低于对照组的23.9%(11/46,P＜0.05).试验组和对照组总体的感染发生率为别为39.5%(17/43)和30.4%(14/46,P＞0.05),两组机会性感染的发生率分另为23.2%(10/43)和17.4%(8/46,P＞0.05).术后3个月内,试验组淋巴细胞计数低于对照组;术后6个月内,试验组CD4+T淋巴细胞ATP值低于对照组.结论 阿来佐单抗行肾移植免疫诱导治疗可维持受者的免疫抑制状态,未见严重不良反应.     

Pediatric liver transplantation with daclizumab induction

BACKGROUND: A new class of monoclonal antibodies (non-T-cell depleting) has gained favor for induction therapy after transplantation. This study evaluated the non-T-cell depleting antibody to the CD25 cell, daclizumab, as a single-dose induction agent immediately after pediatric liver transplantation to spare the use of the calcineurin inhibitor, tacrolimus, for 7 days in respect to both efficacy and renal function. METHODS: From January 1998 to November 2001, 81 pediatric orthotopic liver transplant recipients receiving 89 liver grafts were evaluated. The treatment arm (n=61) received daclizumab 1 mg/kg immediately after liver transplantation along with mycophenolate, steroids, and, on postoperative day 7, tacrolimus. The control group did not receive induction therapy, whereas tacrolimus, mycophenolate, and steroids were started immediately after surgery. RESULTS: The induction group had fewer patients with rejection within the first 30 days after liver transplantation (9 [14.8%] vs. 10 [50%]; P=0.003). The mean time to first rejection was similar between groups (12.1 [+/-7.8] days vs. 18.5 [+/-8.1] days; P=not significant). There was a 3.39 increase in relative risk to develop rejection within the first 30 days after orthotopic liver transplantation if the patient did not receive induction therapy (relative risk=3.39; 95% confidence interval [1.61, 7.14]). Two-year actuarial survival for the induction group was 93.2% compared with 85% in the control; graft survival was also similar between groups (87.8% vs. 72.7%) at 2 years. CONCLUSION: Daclizumab 1 mg/kg given immediately after pediatric liver transplantation and withholding tacrolimus, is safe, efficacious, and reduces rejections within the first 30 days after surgery.     

术前自体骨髓间充质干细胞输注用于肾移植诱导治疗的临床研究

目的 观察骨髓间充质干细胞( BMSC)输注预防肾移植早期急性排斥反应(AR)的有效性和安全性.方法 88例肾移植受者分为BMSC组(43例)和对照组(45例),BMSC组于肾移植当天和术后2周时分别经外周静脉输注自体BMSC,对照组不进行任何诱导治疗.观察两组AR的发生情况、移植肾功能、并发症发生情况,随访时间为24个月.结果 两组患者基本资料的差异无统计学意义(P＞0.05).BMSC组在术后3、6个月AR的发生率分别为4.7％和9.3％,明显低于对照组的20.0％和26.7％(P＜0.05).BMSC组术后7、14和30d的估算肾小球滤过率(eGFR)分别为(1.28±0.62)、(1.33±0.63)和(1.47±0.49)ml/s,明显高于对照组(P＜0.01,P＜0.01,P＜0.05).BMSC组并发症的发生率为44.2％,低于对照组的66.7％(P＜0.05).两组24个月时AR的发生率和eGFR的差异无统计学意义(P＞0.05).两组移植后感染发生率的差异无统计学意义(P＞0.05).结论 术前自体BMSC输注可降低肾移植后早期AR的发生率,可促进移植肾功能早期恢复,安全性较好.     

肾移植术后应用他克莫司的临床观察

目的 观察他克莫司（ＦＫ５０６）作为免疫抑制剂的有效性和安全性。方法 将首次接受同种异体肾移植的３５例患者随机分为２组,一组给予他克莫司,硫唑嘌呤（或霉酚酸酯）和泼尼松（ＦＫ５０６组）,另一组给予环孢素Ａ、硫唑嘌呤（或霉酚酸酯）及泼尼松（ＣｓＡ组）,观察２个组的免疫抑制效果及药物的副作用。结果 ＣｓＡ组和ＦＫ５０６组的人／肾１年存活率分别为１００．０％／９３／３％和９５．０％／９５．０％;两组肝和     

Steroid-Withdrawal at 3 Days After Renal Transplantation with Anti-IL-2 Receptor α Therapy: A Prospective, Randomized, Multicenter Study

Steroids have been included in most immunosuppressive regimens after renal transplantation, but are feared for their side-effects. We conducted a prospective multicenter study to investigate whether it is feasible to withdraw steroids early after transplantation with the use of anti-IL-2Ralpha induction, tacrolimus and mycophenolate mofetil (MMF). A total of 364 patients were randomized to receive either two doses of daclizumab (1 mg/kg) and, for the first 3 days, 100 mg of prednisolone (daclizumab group n = 186), or steroids (tapered to 0 mg at week 16; controls n = 178). All patients received tacrolimus and MMF. The incidence of biopsy-confirmed acute rejection at 12 months was not different between the daclizumab group (15%) and the controls (14%) (95% confidence interval of difference: -6 to + 8%, NS). Graft survival at 12 months was comparable in the two groups (daclizumab group: 91%; controls: 90%). Mean arterial blood pressure, serum lipids, and incidence of patients with hyperglycemia were temporary lower in the daclizumab group compared with controls. The immunosuppressive regimen of the daclizumab group was associated with increased costs. In conclusion, with the use of anti-IL-2Ra induction and daily therapy with tacrolimus and MMF it is feasible to withdraw steroids at 3 days after renal transplantation.     

Incidence of polyomavirus-nephropathy in renal allografts: influence of modern immunosuppressive drugs.

BACKGROUND: In recent years an increasing number of cases with polyomavirus (PV)-nephropathy after renal transplantation were reported from several transplant centres. New, highly potent immunosuppressive drugs like tacrolimus or mycophenolate mofetil were accused as risk factors for this increase. However, data about the incidence of PV-nephropathy in correlation to different immunosuppressive therapy concepts are lacking. METHODS: All renal transplant biopsies performed at Hannover Medical School between 1999 and 2001 (n=1276) were immunohistochemically screened for the presence of PV-specific proteins. The results were correlated to the different immunosuppressive therapy protocols and patients with PV-nephropathy were compared with a matched control group. RESULTS: PV-nephropathy was found in <1% of all investigated allograft biopsies (11/1276) and in approximately 1% of all patients (7/638), respectively. All patients being immunohistochemically positive for PV-specific proteins also showed the typical morphological changes of PV-nephropathy. Four out of seven patients with PV-nephropathy were under triple immunosuppression comprising tacrolimus and mycophenolate mofetil. Under this immunosuppressive therapy protocol an eight times higher incidence and a 13 times higher risk (multivariate odds ratio 12.7) of PV-nephropathy was observed in our patients compared with the control group. CONCLUSIONS: PV-nephropathy is a rare but serious complication after renal transplantation. A small group of patients under intensive immunosuppression comprising tacrolimus in combination with mycophenolate mofetil has a significantly increased risk of acquiring this deleterious complication.     

A novel management strategy of steroid-free immunosuppression after liver transplantation: efficacy and safety of tacrolimus and mycophenolate mofetil

BACKGROUND: Corticosteroids have been used traditionally for immunosuppression after solid organ transplantation. The variety of modern immunosuppressive agents offers the chance to replace drugs with an unfavorable risk-benefit ratio. The objective of this prospective pilot study was to investigate a novel steroid-free immunosuppressive regimen after clinical liver transplantation. METHODS: 30 adult liver graft recipients were included in an intent-to-treat analysis. Dual induction immunosuppression consisted of tacrolimus and mycophenolate mofetil. Prophylactic steroids were not given. Efficacy and safety parameters analyzed were patient and graft survival, incidence and severity of rejection, and adverse events in correlation to immunosuppressive drug levels. RESULTS: Patient and graft survival at 2 years was 86.7 and 83.9%, respectively. Acute rejection occurred in 26.2%, and was associated with subtherapeutic tacrolimus blood levels and diarrhea. All rejections were completely reversible by temporary addition of steroids. Acute renal failure was seen in 10/30 patients, and was related to high tacrolimus blood levels together with primary liver graft dysfunction. 43% of all patients never received any steroids, and 73% were on a steroid-free maintenance regimen. CONCLUSIONS: These results confirm that corticosteroids can be completely avoided from the beginning after liver transplantation. Double drug immunosuppression with tacrolimus and mycophenolate mofetil is effective and safe in terms of patient and graft survival as well as incidence and severity of rejection. In order to avoid under- or over-immunosuppression, which may be caused by impaired absorption or metabolism, close drug monitoring is advised.     

肝移植术后患者应用免疫抑制剂的单中心经验总结(附1400例分析)

目的总结对肝移植术后患者应用免疫抑制剂的经验,探讨个体化治疗的可行性。方法回顾分析2002年4月至2010年8月单中心1400例肝移植患者的临床资料。术后免疫抑制治疗方案的制定按时间发展经历了3个阶段:(1)第1阶段(2002年4月至2004年12月)311例患者采用传统免疫抑制治疗方案;(2)第2阶段(2005年1月至2007年12月)618例患者采用部分传统免疫抑制剂减量的方案;(3)第3阶段(2008年1月至2010年8月)471例患者采用个体化免疫抑制治疗方案。再按术前终末期肝病模型(modelforend-stageliverdisease,MELD)评分及肿瘤是否超出米兰标准分为常规组、超米兰标准组和重症组。收集3个阶段肝移植患者的生存情况,绘制生存曲线。观察第3阶段3组患者的排斥反应发生情况,了解免疫抑制剂其他不良反应及药物替换情况。结果第1、第2、第3阶段患者生存率呈逐渐升高趋势。第3阶段采用个体化治疗,3组的免疫抑制剂用量不同,但3组间免疫排斥反应发生率差异无统计学意义(均为P>0.05)。第3阶段共将12例患者的他克莫司(FK506)转换为环孢素(CsA),32例患者因肾功能损害将FK506转换为小剂量FK506+麦考酚吗乙酯(MMF)或西罗莫司,病情得以缓解。因肿瘤因素或肾功能异常应用单独应用西罗莫司27例,3例因为高脂血症或口腔溃疡不能耐受西罗莫司。结论肝移植术后免疫抑制剂的个体化治疗是可行的,可减少免疫抑制剂的用量,又不增加排斥反应发生率,有利于提高患者生存率。     

Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: one-year results of a 2-center prospective randomized trial

OBJECTIVES: Cyclosporine (INN: ciclosporin) A or tacrolimus have been used mostly in combination with azathioprine as primary immunosuppression after lung transplantation. Benefit or risk deriving from the combination with mycophenolate mofetil are yet unknown. METHODS: In a prospective, 2-center, open randomized trial, the combination of cyclosporine A, mycophenolate mofetil, and steroids was compared with tacrolimus, mycophenolate mofetil, and steroids as primary therapy after primary lung transplantation. All patients underwent induction therapy with rabbit antithymocyte globulin for 3 days. The 2 groups were compared with regard to patient survival, freedom from acute rejection, bronchiolitis obliterans, infectious episodes, and side effects. RESULTS: Between September 1997 and April 1999, 74 lung transplant recipients were randomized to receive either cyclosporine A (n = 37) or tacrolimus (n = 37). Groups were comparable with regard to age, sex, transplant procedure, and cytomegalovirus match. Mean follow-up was 507 +/- 258 and 508 +/- 248 days, respectively. Six- and 12-month survival was similar in both groups (89% vs 84% and 82% vs 71%, respectively; P =.748 at 12 months). Two patients from the cyclosporine A group were retransplanted. Freedom from acute rejection at 6 and 12 months was comparable between groups (46% vs 51% and 35% vs 46%, respectively; P =.774 at 12 months). The mean number of treated acute rejection episodes per 100 patient-days was higher in the cyclosporine A than in the tacrolimus group, but the difference was not statistically significant (0.32 +/- 0.42 vs 0.22 +/- 0.30, respectively; P =.097). Four patients from the cyclosporine A group had to be switched to tacrolimus to control ongoing rejection, whereas no patient from the tacrolimus group had to be switched to cyclosporine A. There was a trend toward more infections (0.7 +/- 0.36 vs 0.55 +/- 0.31, P =.059) in the cyclosporine A group. New-onset diabetes mellitus was observed in the tacrolimus group only (11% vs 0%, P =.151), whereas there was a higher incidence of hypertension (60% vs 11%, P =.03) in the cyclosporine A group. CONCLUSION: This 2-center, prospective randomized study showed high immunosuppressive potency of both cyclosporine A and tacrolimus in combination with mycophenolate mofetil. No significant difference in incidence of acute rejection was observed between the 2 groups. Moreover, survival and incidence of infection were similar. Incidence of drug-related adverse events were similar, yet their spectrum was different.     

Early outcome of different steroid-free regimens in small bowel transplantation: a large-animal study

The intestine is a highly immunogenic organ that requires heavy immunosuppression (IS); therefore corticosteroid withdrawal after clinical small bowel transplantation (SBT) has not been standardized. In this study, we compared different immunosuppressive regimens (none with steroid or induction treatment) in a SBT pig model. Large White unrelated piglets were transplanted and divided into four groups as follow: group 1 (n = 3): no IS; group 2 (n = 10): IS with tacrolimus only; group 3 (n = 10): IS with tacrolimus and mycophenolate mofetil; group 4 (n = 5): IS with tacrolimus and rapamycin. Follow-up time was 30 days. All IS drugs were given orally; tacrolimus whole blood levels ranged between 5 and 15 ng/mL in all groups except for group 2 whose tacrolimus whole blood levels ranged between 15 and 25 ng/mL. Group 1 pigs died of graft acute rejection (ACR) after a median of 12 days. Overall survival in groups 2, 3, and 4 at day 30 was 40%, 80%, and 60%, respectively. Biochemical parameters, including glycemia and cholesterol, were into the normal range with no significant differences between groups. At the end of the study, one animal in group 2 and another one in group 4 showed histological signs of moderate to severe ACR. The incidence of infection was higher in group 2 (2.1 episodes/pig) compared to group 3 (1.25) and group 4 (1.6). This large-animal study demonstrates that tacrolimus-based IS without corticosteroids allows, in the early postoperative period (30 days) after SBT, good survival rates without an increased risk in the incidence of rejection.