Celsior液和UW液保存供肝的前瞻性随机对照研究

目的比较Celsior液和UW液保存供肝的效果。方法随机选取拟行肝移植的患者60例，平均分为两组，一组接受以Celsior液灌洗和冷保存的供肝（Celsior液组）移植，另一组接受以UW液灌洗和冷保存的供肝（UW液组）移植，两组在患者年龄、性别构成、肝功能分级以及原发病、肝移植术式等方面的差异无统计学意义。比较两组供肝组织学变化、术后早期肝功能恢复情况及术后3个月内缺血性胆道狭窄的发生率。结果Celsior液组供肝冷缺血时间为（8．83±1．53）h，UW液组为（9．08±1．85）h，差异无统计学意义（P〉0．05）。两组术后早期血清丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶、胆红素总量、出血时间及胆汁量的差异无统计学意义（P〉0．05），术后3个月内，Celsior液组缺血性胆道狭窄发生率为6．7％（2／30），UW液组为13．3％（4／30），差异无统计学意义（P〉0．05）。两组移植肝的组织学改变相似。结论在冷缺血时间一致的情况下，Celsior液保存供肝的效果与UW液相同。     

一种新型诊断和治疗肝移植术后缺血型胆道病变模式的研究

目的寻找一种用于诊断和治疗肝移植术后缺血型胆道病变（ITBLs）的新模式。方法选取2003年10月至2012年6月在中山大学附属第三医院肝脏移植中心行原位肝移植手术后确诊为ITBLs的80例受者。其中,传统模式组37例受者在出现ITBLs症状后接受药物治疗,明确诊断后行介入治疗和手术治疗,无效者行再次肝移植。早期诊断与干预模式（EDIM）组43例受者接受预防性药物治疗,定期行胆道超声造影,出现ITBLs征象时给予人脐带间充质干细胞移植,明确诊断后行介入治疗和手术治疗,无效者行再次肝移植。采用t检验比较两组受者初诊为ITBLs的时间、采取介入治疗的时间及移植肝丢失时间,采用Kaplan-Meier曲线和Log-Rank法比较两组移植肝1,3年生存率。结果传统模式组受者和EDIM组受者术后初诊为ITBLs的平均时间分别为（56±31）d和（24±19）d,两组比较差异有统计学差异（t=5．136,P〈0．05）。传统模式组和EDIM组从确诊为ITBLs到采取介入治疗的平均时间分别为（105±42）d和（58±20）d,两组比较差异有统计学差异（t=7．035,P〈0．05）。传统模式组和EDIM组死亡受者分别为8例和7例。传统模式组移植肝1,3年生存率分别89．2％,54．1％,EDIM组移植肝1,3年生存率分别95．3％,81．3％,传统模式组受者移植肝1,3年生存率均低于EDIM组（r=4．219,P〈0．05）。传统模式组和EDIM组移植肝丢失时间分别为（25±9）个月和（33±10）个月,传统模式组出现移植肝丢失时问早于EDIM组（t=-2．085,P=0．018）。结论早期诊断和干预ITBLs的新型模式可以延长术后移植肝存活时间,延迟移植肝丢失时间,提高ITBLs的整体治疗效果。     

猪肝移植时无心跳供体耐受热缺血时间的研究

目的 探讨猪肝移植时供肝耐受无心跳热缺血损伤的安全时限。方法 对24头小型家猪根据供肝热缺血时间0、15、30、45min，随机分为4组，而后行原位肝移植，分析移植后肝脏丙氨酸氨基转移酶（ALT）、乳酸脱氢酶（LDH）、三磷酸腺苷（ATP）的含量以及病理变化。结果 WI-45组胆管吻合前无胆汁流出。WI-15、30、45组血清ALT、LDH、肝细胞ATP的含量与WI-0组比较，差异有统计学意义（P〈0．05），WI-15、30组间差异无统计学意义（P〉0．05），但WI-45组与WI-15、30组比较，差异有统计学意义（P〈0．05）。电镜下观察WI-15、30组肝组织呈可复性改变，WI-45组则呈不可逆性改变。结论 猪肝移植时，供肝耐受无心跳热缺血损伤的的安全时限为30min。     

肝移植术中复杂的肝动脉重建

目的 探讨供肝肝动脉解剖变异的整形重建方式及对移植后肝动脉血栓形成（HAT）、胆道并发症及移植疗效的影响。方法 回顾性分析1999年5月至2005年9月完成的330例原位肝移植临床资料。应用显微外科技术对变异肝动脉进行整形。供肝肝动脉整形、重建及供受者问动脉的吻合在2．5倍放大镜下以7-0、8-0 Prolene或Vascufil缝线完成。术后每日用多普勒超声检查肝动脉血流1周，其后定期监测。结果 67例供肝肝动脉存在解剖变异，占20．5%（67／327），实施血管重建性吻合79例次。存在动脉变异供肝附加血管整形重建组围手术期HAT发生率与无肝动脉变异供肝肝移植组围手术期HAT发生率比较（1．5％7351．15％）；随访期内胆道并发症发生率与无肝动脉变异供肝肝移植组发生率比较（9．0％vs7．7%），均无显著差异（P〉0．05）。两组受者比较，1、3年生存率无显著差异（91．3％vs90．7％，86．7％vs88．2％）（P〉0．05）。结论 应用存在肝动脉变异并血管整形的供肝，实施肝移植不增加HAT及胆道并发症发生率，并可取得与无变异肝动脉供肝相同的远期疗效。     

成人活体肝移植单中心56例临床报告

目的探讨成人间右半肝移植手术中保证供、受者安全的方法。方法2002年1月至2006年9月四川大学华西医院对56例受者施行了成人右半肝移植,其中52例不含肝中静脉,4例双供肝肝移植。受者原发病为乙型肝炎肝硬化35例（62．5％,含急性肝功能衰竭12例）,肝细胞肝癌17例（30．4％）,其他4例;MELD评分〉25分者10例。供者常规行三维CT计算全肝体积及右半肝体积,并进行了移植手术技术改进。结果58例供者共摘取55例右半供肝及3例左半供肝。右半供肝均不含肝中静脉,重量为400—860g（中位数550g）,右半供肝与受者标准肝重比为31．7％-71．7％（中位数45．4％）,供者残肝体积均大于全肝体积的35％。58例供者发生并发症7例（12．5％）,无死亡。术后住院时间7—30d（中位数11d）。术后对56例受者随访2—52个月（中位数11个月）,发生并发症15例（26．8％）,死亡4例（7．2％）。1年实际生存率92．8％。结论采用不包含肝中静脉的右半供肝,术前CT测量残肝体积〉35％,同时右半供肝与受者标准肝重比〉40％者进行右半肝移植可保证供受者安全,反之则应考虑采用双供肝肝移植。     

脂肪变性供肝肝移植受者预后分析的多中心临床研究

目的探讨脂肪变性供肝肝移植的早期与中长期疗效, 提出临床应用优化策略。方法采用回顾性队列研究方法。收集2015年1月至2020年12月树兰(杭州)医院、浙江大学医学院附属第一医院、吉林大学第一医院3家医学中心1 535例肝移植受者的临床病理参数和随访资料。此观察性研究采用倾向性评分匹配两组受者, 以减少受者基线水平的选择偏移, 匹配后两组基线数据差异无统计学意义。根据是否使用脂肪变性供肝分成脂肪变性供肝组(243例)和非脂肪变性供肝组(1 292例), 进行倾向性评分1∶1匹配研究, 对比分析两组肝移植受者的早期和中长期疗效差异。采用Kaplan-Meier法计算生存率和绘制生存曲线, 采用Log-Rank检验进行生存分析。进一步通过单因素及多因素Cox回归分析, 确立影响移植疗效的独立危险因素。根据术前合并基础代谢病的情况, 将接受脂肪变性供肝受者分为3个亚组:体重指数(body mass index, BMI)≥25 kg/m2且有高血压病或糖尿病21例、BMI<25 kg/m2且没有高血压病和糖尿病130例和其他92例。基于受者和供肝的不同特征, 开展脂肪变性供肝受者不同亚...     

脂肪变性供肝对儿童活体肝移植供受者预后的影响

目的探讨脂肪变性供肝对儿童活体肝移植供者的安全性及供受者预后的影响。方法回顾性分析2013年1月至2020年12月天津市第一中心医院器官移植中心儿童器官移植科完成的814例儿童活体肝移植中供者和受者的临床资料。根据供肝是否存在脂肪变性将供者和受者分为非脂肪变性供肝组(n=733)和脂肪变性供肝组(n=81), 根据脂肪变性程度将脂肪变性供肝组再分为轻度及中度脂肪变性两个亚组。非脂肪变性供肝组供者中, 男性307例, 女性426例, 中位年龄30岁(范围:18～57岁);受者中男性351例, 女性382例, 中位年龄7个月(范围:4个月至14岁)。脂肪变性供肝组供者中, 男性41例, 女性40例, 中位年龄31岁(范围:22～51岁);受者中男性34例, 女性47例, 中位年龄8个月(范围:5个月至11岁)。术后通过门诊复查、问卷调查等方法对供受者进行定期随访。分别使用t检验、Wilcoxon秩和检验、重复测量方差分析、χ2检验或Fisher确切概率法对各组数据进行统计学分析。采用Kaplan-Meier法绘制各组中受者和移植物生存曲线, 并应用Log-rank检验比较脂肪变性供肝组和非...     

大鼠供肝冷保存时间延长损伤移植肝肝细胞和肝窦内皮细胞

目的 探讨供肝冷保存时间与肝移植后肝细胞和肝窦内皮细胞（SEC）损伤的关系。方法 选取健康雄性SD大鼠作为供、受者，建立原位肝移植（OLT）模型。随机分为3组，冷保存1h组（H=48）：供肝获取后，置于4C的冷保存液中保存1h，再行OLT。冷保存12h组（n=48）：供肝获取后，置于4℃的UW液中保存12h，再行OLT。对照组（H=6）：大鼠只打开腹腔，不进行移植。前2组分别于术后1、6、12、24、48、72、96和168h采取血液及组织标本，对照组仅在开腹时取血液及组织标本，检测各组、各时点血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）及透明质酸（HA）的水平；观察移植肝的病理形态学变化，透射电镜观察其超微结构改变；原位末端脱氧核糖核酸转移酶标记法（TUNEL）检测移植肝细胞的凋亡情况；观察术后168h时的大鼠存活率。结果 冷保存1h和冷保存12h组肝移植后各时点血清ALT、AST及HA均较对照组明显升高（P〈0．05），并且冷保存12h组又明显高于冷保存1h组（P〈0．05）。冷保存12h组术后24h移植肝组织出现片状坏死，而冷保存1h组病理学改变不明显。冷保存12h组肝窦内皮细胞凋亡指数（AI）明显高于冷保存1h组（F=63．58，P〈0．01），两组大鼠移植肝组织均于术后6h出现凋亡高峰，且肝窦内皮细胞的凋亡指数明显高于肝细胞。冷保存1h组和冷保存12h组大鼠肝移植后168h时的存活率分别为100％和50％，两组比较，差异有统计学意义（F=6．39，P〈0．05）。结论 肝移植后肝细胞和肝窦内皮细胞的损伤程度与冷保存时间密切相关。肝窦内皮细胞对冷保存及再灌注损伤的敏感性高于肝细胞，其损伤方式以细胞凋亡为主。     

脂肪变性供肝在背驮式肝移植中的应用

目的 探讨脂肪变性供肝(SLD)在背驮式肝移植中的应用.方法 将64例SLD进行了背驮式肝移植,其中脂肪变性程度分级为轻(S1级)、中(S2级)、重(S3级)者分别为22、25和17例,随机抽出同期80例供肝无脂肪变性者作为对照.观察手术当天受者的肝、肾功能,术后近期肝功能恢复情况,术后1个月的并发症发生情况,以及受者的死亡情况.结果 与对照组比较,手术当天各级脂肪变性组的肝、肾功能的差异均无统计学意义(P＞0.05).术后21 d,对照组95％受者的肝功能恢复正常,S1级组、S2级组和S3级组分别为90.9％、80.0％和70.6％,S3级组有2例(11.8％)发生移植物原发性无功能.S1、S2和S3组分别与对照组比较,出血、感染、肝动脉栓塞、腹水、败血症等并发症发生率的差异有统计学意义(P＜0.05).术后1年内,对照组死亡2例,S1级组死亡1例,S2级组死亡1例,S3级组死亡5例.结论 SLD可以用于移植,但对重度脂肪变性肝脏的移植,即使在目前供者紧张的情况下,也应审慎进行.     

30例肝移植病例MELD分析

目的探讨终末期肝病模型（MELD）评分评估终末期肝病患者行肝移植术后,受者短期预后、肝移植的手术时机以及MELD与肝脏病理的关系。方法对30例肝移植病例进行回顾性分析,比较术后随访30天后存活组（12例）与死亡组（18例）的术前MELD评分,以MELD分值25和30为界线将病例分组,比较存活率以及肝脏病理,分析大块、亚大块肝细胞坏死与非大块、亚大块肝细胞坏死病例的MELD分值。结果所有患者术前MELD评分平均值为28．92±13．45,术后随访3个月总生存率为40％,其中存活组与死亡组术前MELD评分分别为21．56±11．83和33．82±12．43（P〈0．05）;以MELD评分25为界将患者分为两组,术后3个月存活率为63．6％和26．3％（P〈0．05）;以MELD评分30为界将患者分为两组,术后3个月存活率为53．3％和26．7％（P〉0．05）：大块、亚大块肝细胞坏死组与非大块、亚大块肝细胞坏死组患者术前MELD值相比有显著差异,分别为22．38±12．69和33．28±12．41（P〈0．05）。结论MELD评分可评估肝移植受术者的短期预后,肝移植受者MELD评分值在25分时比30分时行肝移植术更有意义,MELD评分与肝细胞坏死面积有关。     

脂肪供肝对肝移植术后早期肝功能和预后的影响

目的 探讨脂肪供肝对肝移植术后早期肝功能和半年预后的影响.方法 中山大学附属第一医院近3年使用UW液体灌注的首次肝移植患者76例,其中脂肪供肝35例,按肝脂肪变性程度分3组(＜20%组,20%～40%组,≥40%组),无脂肪变性供肝41例为对照组,分别比较各组术后当天、1、2、3、7 d的丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平、总胆红素(TB)、凝血酶原时间(PT),ICU时间、迟发性无功能(DNF)发生率和3、6个月患者生存率等各项指标.并对35例脂肪变性供肝程度和术后肝功能关系进行相关性分析. 结果肝脂肪变性≥140%组的术后ALT、AST、TB、PT均高于脂肪变性20%～40%组,脂肪变性20%～40%组术后的AST,ALT,TB均高与脂肪变性＜20%,供肝脂肪变性＜20%组各项指标与对照组差异不显著,各组术后DNF发生率和3、6个月存活率均无统计学差异.脂肪变性程度和术后肝功能的相关性分析显示,随脂肪变性程度增大,肝功能损害逐步加重,相关性有显著意义.结论 供肝脂肪变性＜20%对肝移植术后肝功能影响较小,作为供肝较为安全;供肝脂肪变性≥20%对肝移植术后肝功能损害明显加重,增加术后肝功能衰竭的风险,应慎重使用;对脂肪变性≥40%供肝应更慎重或避免使用.     

The hepatic regeneration power of mild steatotic grafts is not impaired in living-donor liver transplantation.

The aim of this study was to assess histologic changes in steatotic grafts, regenerative capacity, and the outcome of steatotic grafts in living-donor liver transplantation (LDLT). Between September 2002 and February 2004, 55 cases of LDLT with a liver biopsy performed on the 10th postoperative day were enrolled. Patients were grouped according to the intraoperative histologic degree of macrovesicular steatosis (MaS) as follows: Group 1, <5% (n = 24); Group 2, 5 to 15% (n = 24); and Group 3, 15 to 30% (n = 7). The intraoperative microscopic findings and the findings on the 10th postoperative day were compared. Immunohistochemistry was performed using antibody of proliferating cell nuclear antigen (PCNA) and Ki-67 to assess the regeneration power of grafts on the 10th postoperative day. The histologic degree of MaS on postoperative day 10 decreased from 5.22 +/- 1.04% (mean +/- standard deviation) to 2.17 +/- 1.90 in Group 2 (P < .001) and from 21.4 +/- 8.02 to 4.43 +/- 2.70 in Group 3 (P = .003). The number of positively stained hepatocytes in 10 high power fields was 48.0 +/- 17.1, 53.8 +/- 14.4, and 51.5 +/- 4.1 in each group by PCNA (P = .681), and 24.0 +/- 14.0, 25.5 +/- 11.8, and 21.6 +/- 6.8 by Ki-67 (P = .825), respectively. No primary graft nonfunction (PNF) or delayed graft function (DGF) occurred. Major complications were comparable among groups. In conclusion, in LDLT, steatosis disappeared immediately after transplantation and hepatic regeneration power was not impaired in grafts with less than 30% of MaS. Furthermore, a mildly steatotic graft did not increase the risk of graft dysfunction or morbidity in LDLT.     

大鼠小体积肝脏移植后早期肝内细胞因子的变化

目的 研究不同冷缺血条件下大鼠小体积肝移植(30%标准体积)后早期肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)的变化,及其与肝脏再生的关系.方法 建立Lewis大鼠30%标准体积的原位肝移植模型.根据供肝在UW液中冷保存时间的不同,将受者分为3组:冷缺血1 h组、冷缺血8 h组和冷缺血16 h组,每组均为20只.观察受者存活情况至术后第7天,并分别在移植肝恢复血流后90 min、1 h、2 h、4 h和7 d收集样本,检测移植肝组织中TNF-α和IL-6表达情况,肝细胞DNA的合成情况,进行移植肝的形态学观察.结果 大鼠肝移植手术成功率均为100%.移植后第7天,冷缺血1 h和8 h组受鼠的存活率均为100%.冷缺血16 h组受鼠的存活率较低,移植后第7天无受鼠存活.冷缺血1 h组TNF-α和IL-6的表达水平较低,冷缺血8 h组和冷缺血16 h组TNF-α和IL-6的表达则高于冷缺血1 h组(F=58.81和F=184.12,P<0.05).冷缺血8 h组和冷缺血16 h组间TNF-α和IL-6的表达的差异无统计学意义.冷缺血1 h组增殖细胞数目明显高于冷缺血8 h组,差异有统计学意义(t=5.59,P<0.05).移植术后24h,冷缺血1 h组移植肝有轻度的组织学损伤;冷缺血8 h组移植肝有轻度的窦状隙扩张和轻度的炎症;冷缺血16 h组移植肝有局部淤血,存在肝细胞崩解和坏死等改变.结论 在小体积肝移植后早期,TNF-α和IL-6的上调表达对肝脏再生有重要意义.不同冷缺血时间的小体积肝脏移植物内存在早期启动肝脏再生的信号.     

冷缺血对大鼠小体积肝移植肝再生的影响

目的探讨冷缺血对大鼠小体积肝移植术后肝再生的影响.方法本组在2002年9月～2004年8月利用大鼠肝总量30%原位肝移植模型,实验分为肝总量70%肝切除组(C组)和冷缺血1、3、5 h组(E1、E2、E3组),观察1w生存率及肝重量/受体原肝重量比值(EGW/RLW),并检测术后1、2、3、7d肝细胞增殖活性及肝组织学变化.结果E1组1w生存率及EGW/RLW分别达100%和95%,均明显高于E2、E3组(P均＜0.05);E1、E 、E3组均于术后2d达到增殖高峰,其中E1组峰值显著高于E2、E3组(P＜0.001),且与C组峰值无差异(P＞0.05);组织学检查见E1组肝细胞核分裂明显活跃.结论冷缺血1 h的小体积供肝和70%肝切除后肝脏具有同样的增殖活性,仅增殖高峰稍晚;冷缺血超过3h严重影响小体积供肝的再生能力和受者的存活率.     

Orthotopic liver transplantation in fulminant and subfulminant hepatitis. The Paul Brousse experience.

OBJECTIVE: The authors report on the experience of orthotopic liver transplantation in fulminant hepatitis at Paul Brousse Hospital. SUMMARY BACKGROUND DATA: Liver transplantation is a breakthrough in the treatment of patients with fulminant hepatitis. However, the indications, the timing for transplantation, the type of transplantation, and the use of ABO incompatible grafts in this setting still are debated. METHODS: Transplantation was indicated in patients with confusion or coma and factor V less than 20%, younger than 30 years of age, and confusion or coma and factor V less than 30% older than 30 years of age. RESULTS: Among 139 patients who met the aforementioned criteria for transplantation, 1 recovered, 22 died before transplantation, and 116 underwent transplants with a 1-year survival of 68%. Survival was 83% in patients with grade 1 and 2 comas at transplantation versus 56% (p < 0.001) in those with grade 3 comas; it was 51% versus 81% (p < 0.001) in those transplanted with high risk (ABO-incompatible, split, or steatotic) and low-risk grafts, respectively. In a multivariate analysis, steatotic and partial grafts were predictive of poorer patient survival, and ABO incompatibility was predictive of poorer graft survival. CONCLUSIONS: Orthotopic liver transplantation is an effective treatment in fulminant hepatitis. Use of high-risk grafts permitted transplantation of 83% of patients, but was responsible for higher mortality.     

自体骨髓细胞诱导肝移植大鼠长期存活的机制探讨

目的 研究自体骨髓细胞诱导肝移植大鼠长期存活的可能机制.方法 雌性受体大鼠随机分成空白对照组(A组)、D-hanks液组(B组)、全骨髓细胞组(C组)、间充质干细胞组(D组).观察大鼠的中位生存时间(median survival time,MST)、肝功能、病理变化、Sry基因原位杂交和甲胎蛋白、白蛋白免疫组化双标检测观察自体骨髓细胞的分化情况.结果 C组、D组MST均>180 d(P<0.01);血肝功能指标C组、D组降低明显,有显著差异(P<0.01);C组、D组之间比较无显著差异(P>0.05);移植术后60 d C、D组均无明显的急性排斥反应;C组、D组Sry基因原位杂交和甲胎蛋白、白蛋白免疫组化双标检测呈阳性.结论 自体骨髓细胞能减少排斥反应、诱导大鼠肝移植术后长期存活,其中间充质干细胞在移植肝内诱导分化为肝细胞发挥肝细胞功能,是其中可能的机制.     

Use of severely steatotic grafts in liver transplantation: a matched case-control study

BACKGROUND: Although there is a worldwide need to expand the pool of available liver grafts, cadaveric livers with severe steatosis (>60%) are discarded for orthotopic liver transplantation (OLT) by most centers. METHODS: We analyzed patients receiving liver grafts with severe steatosis between January 2002 and September 2006. These patients were matched 1:2 with control patients without severe steatosis according to status the waiting list, recipient age, recipient body mass index (BMI), and model for end-stage liver disease (MELD) score. Primary end points were the incidence of primary graft nonfunction (PNF), and graft and patient survival. Secondary end points included primary graft dysfunction (PDF), the incidence of postoperative complications, and histologic assessment of steatosis in follow-up biopsies. We also conducted a survey on the use of grafts with severe steatosis among leading European liver transplant centers. RESULTS: During the study period, 62 patients dropped out of the waiting list and 45 of them died due to progression of disease. Of 118 patients who received transplants 20 (17%) received a graft with severe steatosis during this period. The median degree of total liver steatosis was 90% (R = 65%-100%) for the steatotic group. The steatotic (n = 20) and matched control group (n = 40) were comparable in terms of recipient age, BMI, MELD score, and cold ischemia time. The steatotic group had a significantly higher rate of PDF and/or renal failure. Although the median intensive care unit (ICU) and hospital stay were not significantly different between both groups, the proportion of patients with long-term ICU (> or =21 days) and hospital (> or =40 days) stay was significantly higher for patients with a severely steatotic graft. Sixty-day mortality (5% vs. 5%) and 3-year patient survival rate (83% vs. 84%) were comparable between the control and severe steatosis group. Postoperative histologic assessment demonstrated that the median total amount of liver steatosis decreased significantly (median: 90% to 15%, P < 0.001). Our survey showed that all but one of the European centers currently reject liver grafts with severe steatosis for any recipient. CONCLUSION: Due to the urgent need of liver grafts, severely steatotic grafts should be no longer discarded for OLT. Maximal effort must be spent when dealing with these high-risk organs but the use of severely steatotic grafts may save the lives of many patients who would die on the waiting list.     

Therapeutic Targets in Liver Transplantation: Angiotensin II in Nonsteatotic Grafts and Angiotensin-(1–7) in Steatotic Grafts

Numerous steatotic livers are discarded as unsuitable for transplantation because of their poor tolerance of ischemia-reperfusion(I/R). The injurious effects of angiotensin (Ang)-II and the benefits of Ang-(1–7) in various pathologies are well documented. We examined the generation of Ang II and Ang-(1–7) in steatotic and nonsteatotic liver grafts from Zucker rats following transplantation. We also studied in both liver grafts the effects of Ang-II receptors antagonists and Ang-(1–7) receptor antagonists on hepatic I/R damage associated with transplantation. Nonsteatotic grafts showed higher Ang II levels than steatotic grafts, whereas steatotic grafts showed higher Ang-(1–7) levels than nonsteatotic grafts. Ang II receptor antagonists protected only nonsteatotic grafts against damage, whereas Ang-(1–7) receptor antagonists were effective only in steatotic grafts. The protection conferred by Ang II receptor antagonists in nonsteatotic grafts was associated with ERK 1/2 overexpression, whereas the beneficial effects of Ang-(1–7) receptor antagonists in steatotic grafts may be mediated by NO inhibition. Our results show that Ang II receptor antagonists are effective only in nonsteatotic liver transplantation and point to a novel therapeutic target in liver transplantation based on Ang-(1–7), which is specific for steatotic liver grafts.     

Pseudomonas aeruginosa bacteremia in patients undergoing liver transplantation: an emerging problem

In our institution, Pseudomonas aeruginosa bacteremia appeared to occur with increasing frequency in patients undergoing liver transplantation. We thus conducted a prospective study to define risk factors and outcome in these patients. Over a 19-month period 6% of liver transplants were followed by Pseudomonas bacteremia. The mean age was 46 years (range, 24 to 67 years). The interval between transplantation and onset of bacteremia was 3 to 372 days (mean, 80). The incidence of Pseudomonas bacteremia in liver transplants was three times that of other transplants (heart, lung, kidney). Ninety one percent of infections were nosocomial. Polymicrobial bacteremia occurred in 30% of episodes. The portal of entry was respiratory in 30%, abdominal in 35%, and biliary in 13%. Four patients had recurrent Pseudomonas bacteremia: liver abscess (1), biliary obstruction (2), subhepatic abscess (1). Survival at 14 days was 70%. Survival rates were significantly lower for patients with hypotension, on mechanical ventilators, and increasing severity of illness (p less than 0.05). Survival was higher when bacteremia occurred within the first 30 days after transplantation compared to after 30 days. A large number (43.4%) of Pseudomonas bacteremias occurred after transplant surgery of biliary tract manipulation, while the patient was receiving a prophylactic regimen of cefotaxime and ampicillin. P. aeruginosa is an important pathogen in the liver transplant recipient; prevention may be possible for a subgroup of patients with the use of prophylactic antibiotics with activity against P. aeruginosa.     

Resolution of severe graft steatosis following dual-graft living donor liver transplantation.

Although severely steatotic liver grafts are not suitable for transplantation, they have been used when other, more optimal donors were not available, especially for living donor liver transplantation (LDLT) using two liver grafts. Here we present two cases of dual-graft LDLT in which the recipients showed rapid and complete clearing of fat from livers with previously severe steatosis. In the first case, two left lateral segment grafts were used, one of which was 70% steatotic. Preoperative and posttransplant two-week liver-to-spleen computed tomography-value (L/S) ratios were 0.48 and 1.25, respectively. A liver biopsy taken two weeks after transplantation showed that the fatty changes had almost disappeared. The second case used one left lobe and one left lateral segment graft, the latter of which was 80% steatotic. Preoperative and two-week L/S ratio were 0.58 and 1.34, respectively, and a liver biopsy taken two weeks after transplantation showed less than 3% steatosis. The two donors of the severely steatotic liver grafts recovered uneventfully. These findings show that the fat content of the liver grafts was rapidly removed after transplantation. This observation is helpful in understanding the recovery sequences following transplantation of steatotic liver grafts, as well as expanding the acceptability of steatotic liver grafts.