ABO血型不合肝移植研究新进展

复习国外文章关于ABO血型不相同的肝脏移植在A2型供肝使用，移植肝出现受体类型的ABO组织血型抗原，C4d作用和临床治疗上的新进展。A2型供肝能较安全的用于血型不合肝移植，毛细血管内表达r-ABOAg可能是移植物内皮损害和修复的表现，C4d阳性对血型不同肝移植治疗策略上是很好的参考物，但缺乏特异性，采用包括多联免疫抑制药和肝内灌注等综合治疗方法能有效预防排斥反应且能取得良好的预后。     

ABO血型不相容活体肾移植的热点评析

<正>同种异体肾移植术是治疗各种终末期肾病的最佳方法。近年来尸体供肾逐渐紧张,供体短缺的矛盾日益突出,大力发展亲属活体肾移植是解决这一矛盾的重要途径。国外统计资料显示,在潜在的活体供者中,大约有30%的供者与受者ABO血型不相容,即供者血型和受者血型不符合输血原则[1]。在ABO血型不相容的活体肾移植中,如果术前不     

ABO血型基因与移植肾急性排斥反应相关性的研究

目的 探讨ABO血型基因与移植肾急性排斥反应(AR)的相关性.方法 采用引物特异性聚合酶链式反应(PCR-SSP)技术检测2009年5月至2010年2月87例肾移植受者及其对应的48例供者ABO(A1、A2、B、O1、O2)血型基因,分析供受者ABO血型基因相合组与错配组受者AR发生、治疗及转归情况.结果 PCR-SSP测定ABO血型基因推定的表型和血清学方法测定ABO血型表型完全相符.供受者ABO血型基因相合组受者50例,发生AR 6例,经甲泼尼龙(MP)冲击治疗后临床逆转.ABO血型基因错配组受者37例,发生AR 11例,经MP冲击治疗后,临床逆转10例,周期性反复发生AR 1例.错配组与相合组受者AR发生率差异有统计学意义(29.7%与12.0%,P<0.05).错配组1例A2O1血型基因受者接受A1O1血型基因供肾后,受者血清检测发现抗A1抗体,抗体效价IgG 1:64,IgM 1:16,移植术后3～10个月周期性反复发生AR,且周期逐渐变短,激素疗效逐渐降低,术后1年SCr达441μmol/L.结论 检测供受者HLA时同步检测ABO血型基因具有很强的可行性.A2血型基因受者适宜选择O型供肾.供受者ABO血型基因错配是介导肾移植术后AR的危险因素,检测供受者ABO血型基因,降低ABO血型基因错配率对预防AR有一定的临床意义.     

儿童ABO血型不相容活体肝移植术后供者血型抗原不完全免疫耐受状态的研究

目的结合临床数据及文献分析儿童ABO血型不相容活体肝移植针对血型抗原低免疫应答状态的潜在免疫机制。方法回顾性收集首都医科大学附属北京友谊医院2013年6月至2020年12月期间施行的术后长期生存的儿童ABO血型不相容活体肝移植受者29例, 受者血型均为O型, 其中A型供者10例, B型供者19例。移植物类型包括左外侧叶26例, 左半肝3例;肝移植手术中位年龄10月龄, 中位体重为8.0 kg, 中位随访时间41.9个月。连续监测移植术前及移植术后1、3、6、12、24、36个月受者体内针对供者血型相关抗体与供者血型非相关抗体滴度(IgG、IgM), 并进行比较分析。对纳入受者进行程序性肝脏病理穿刺活检或事件性肝脏病理穿刺活检判断是否存在抗体介导排斥反应。结果受者移植术前及术后血型抗体(IgG、IgM), 受者体内抗供者血型相关抗体滴度呈持续低水平状态, 较体内非供者血型相关抗体滴度水平显著降低, 差异有统计学意义(P<0.001)。对于纳入研究的29例受者, 共有18例完成程序性肝脏病理活检, 其中2例提示血管内皮C4d阳性;5例完成肝功能异常事件性肝脏病理活检, 其中1例存在胆...     

ABO血型在结直肠癌中的意义的研究进展

目的 了解当前研究中有关ABO血型抗原在结直肠癌（colorectal cancer,CRC）的发生、发展、筛查、治疗和预后中的作用。方法 对国内外有关ABO血型与CRC相关关系研究的文献进行综述并分析。结果 ABO血型抗原与CRC发生的关系可能有两种相关机制，即ABO血型抗原调控基因上的核苷酸多态性和ABO血型抗原表达的丧失，其中它在癌细胞中的异常表达机制为CRC的筛查提供线索，而目前在治疗和预后方面仅有部分研究发现了ABO血型与此有关，但并未阐明其详细机制。结论 从总结的文献结果看，目前已有研究者对ABO血型在CRC发生中的作用进行了研究且得到了一些ABO血型抗原在CRC的发生、发展、筛查、治疗和预后中有临床意义的结论，提示具有一定的研究前景。但由于相关研究较少，得到的结论还需要进一步验证。     

ABO血型不合肝移植研究进展

根据供／受体ABO血型配合情况，可以将其分为ABO血型相同、ABO血型相符和ABO血型不合。数据统计表明：ABO血型不合肝移植术后发生急性排斥反应、肝叶坏死和血管、胆道并发症均较血型相符者多。但是，肝脏作为一“免疫特惠器官”，对抗体介导的损伤有较好的耐受性，极少发生超急性排斥反应。匹兹堡UNOS肝移植登记处的资料显示，7000余例成人肝移植中ABO血型不合者占3％，在1500例小儿肝移植中占7％。在欧洲，8％的急诊肝移植为ABO血型不合。因此，在紧急或供体紧缺的情况下行ABO血型不合的肝移植已逐渐被接受。     

Rh阴性受者接受Rh阳性供肾移植一例

患者为男性，39岁，原发病为慢性肾小球肾炎、尿毒症，接受血液透析1年余，群体反应性抗体阴性。患者的ABO血型为B型，RhD阴性，其表型为Ccdee，该表现型在我国汉族人的Rh表型频率为0．0008。术前Rh抗体检测：抗E阴性，抗D阴性，抗C阴性，抗e阴性。供者的ABO血型为B型，RhD阳性，供、受者HLA—A、B、DR位点有4个抗原相合，     

跨ABO血型肾移植

ABO血型障碍是抑制肾移植发展的主要因素,通过各种措施来控制和避免跨ABO血型肾移植术后的排斥反应,延长移植肾的存活时间,保护移植肾功能,有利于解决移植肾供体短缺的状况.本文就跨ABO血型肾移植的历史、抗排斥策略、优越性、存在问题和发展方向进行综述.     

腹腔器官移植供受者ABO血型基因型及其随机错配率的研究

目的 探讨腹腔器官移植供、受者的ABO血型基因型的分布频率,分析移植供、受者在ABO血清型相同的基础上的基因型随机错配情况.方法 肾移植受者89例、肝移植受者22例为受者组,同期86名无关随机供者为供者组.两组均采用单克隆抗体检测ABO血清学分型,同时采用聚合酶链反应-序列特异性引物(sequence-specific...     

ABO血型不相容肾移植术后并发过客淋巴细胞综合征一例并文献复习

正供肾来源短缺是目前制约肾移植发展的主要瓶颈,ABO血型不相容肾移植(ABO-incompatible kidney transplantation,ABOi-KT)是缓解供肾来源短缺的重要方式之一。已有部分终末期肾病患者接受ABOi-KT,且术后生存率逐步提高。少数行ABOi-KT的受者术后并发过客淋巴细胞综合征(passenger lymphocyte syndrome,PLS),主要表现为移植术后血红蛋白短期内迅速下降,其原因为供者来源淋巴细胞分泌的血型抗体针对受者抗原产生免疫反应,引起以     

Increased bile duct complications in liver transplantation across the ABO barrier.

OBJECTIVE: This study evaluated the outcome of liver grafts from ABO incompatible donors, focusing on biliary complications, and compared the results to an ABO compatible control group. Also, the expression of donor ABH antigens in the liver graft was analyzed. SUMMARY BACKGROUND DATA: The outcome of liver transplantation using an ABO incompatible graft is still debated. These blood group related (ABH) antigens are known to be expressed not only on the surface of the erythrocytes, but also on the epithelial cells of large bile ducts. Because the biliary epithelium of hepatic allografts may continue to express donor ABH antigens, it may be more susceptible to immunologic bile duct injury after transplantation across the ABO barrier. METHODS: Eighteen ABO incompatible grafts were compared with 18 ABO compatible grafts in patients who were matched according to medical urgency, primary liver disease (PLD), and recipient age. After transplantation, the grafts were analyzed with cholangiography, Doppler ultrasound, or arteriography and liver histology according to protocol. Immunoperoxidase staining for ABH antigens was performed on hepatic tissue. RESULTS: Biliary complications developed in 82% of the ABO incompatible donors, compared to 6% of the ABO matched controls. Hepatic artery thrombosis occurred in 24%. Cellular rejection was diagnosed in 65% versus only 28% in the control group. The 1-year actuarial graft survival rate was 44% versus 78% in the control group. ABH antigens of the donor were expressed on vascular endothelium and bile duct epithelial cells as long as 150 days after transplant. CONCLUSIONS: Using ABO incompatible allografts, a high incidence of biliary and hepatic artery complications and decreased graft survival in liver transplantation were found. An immunologic injury to the bile duct epithelium and/or to vascular endothelium is suspected.     

成人间活体右半肝移植术中变异门静脉右支切取与重建技术

目的 探讨成人间活体右半肝移植术中变异门静脉支(APVB)切取与重建的技巧.方法 2002年1月至2007年4月,共实施70例成人间活体右半肝移植.术前肝脏血管三维CT成像显示供肝动脉及静脉走向,70例右半供肝中有9例门静脉分支变异,其中7例为Ⅱ型变异,2例为Ⅲ型变异.除1例供者行狭窄桥状连接单口切取APVB外,其余8例均采用供者优先的原则即距门静脉主干2～3mm处双口切断APVB.Ⅱ型变异中有2例双口切取其右前、右后支成形为一个开口后与受者门静脉主干吻合,4例右前、右后支分别与受者门静脉左、右支吻合,1例行右前、右后支间狭窄桥状组织连接单口切取后与受者门静脉主干单口吻合.Ⅲ型变异中有1例双口切取其右前、右后支分别与受者门静脉支双口吻合,1例双口切取后行新型的U形血管移植物间置与受者门静脉主干单口吻合.结果 9例受者均无门静脉狭窄或血栓、肝动脉狭窄或血栓以及肝静脉流出道狭窄等血管并发症发生.1例供者术后3 d并发门静脉血栓,手术取栓及门静脉壁修补成形后痊愈.新型的U形血管移植物间置重建术后通畅,无并发症发生.结论 成人间活体右半肝移植术中采用供者优先的原则双口切取APVB、双口吻合重建以及新型的U形血管间置等门静脉重建技术是安全可行的,未增加手术难度,且临床效果良好.     

The feasibility of in vivo resection of the left lobe of the liver and its use for transplantation

The anatomical possibility of resecting the left lobe of the liver (segments II and III) in living subjects and using it for transplantation was evaluated. A group of 60 cadaveric livers were dissected at autopsy. The vascular and biliary elements of the left lobe were isolated and the lobe was resected and evaluated for possible grafting. The left lobe was 12-28% (mean 19.4%) of the liver mass. An extrahepatic segment of the left hepatic vein was isolated in 95% of specimens. Arterial blood supply to the left lobe consisted of a single artery (92%) or two arteries (8%). A single portal vein segment to the left lobe (type I) was found in 35% livers. Portal vein branches originated from a common orifice (type II, 35%) or separately (type III, 30%) from the left portal vein, and in these instances, preparation of a portal segment necessitated partial section of the left portal vein wall. Biliary drainage was extrahepatic in 56 livers and consisted of a single duct (type I, 78%), or two ducts (type II, 15%). The resected left lobe was evaluated as satisfactory (single hepatic vein and artery, types I or II portal vein, type I bile duct) in 48% of cases, while a less-satisfactory lobe (type III portal vein or type II bile duct) was obtained in 33%. It was found anatomically difficult or impossible to resect the left lobe for possible transplantation in 11 (19%) liver specimens.     

Changes in hepatic ultrastructure and function following portal vein resection with a use of an internal shunt bypass

Experimental studies on ultrastructural and functional changes of mitochondria were carried out using adult dog livers after portal vein resection with an internal shunt bypass. As a comparative study portal vein resection with an external shunt bypass was also carried out. A 10 cm long anti-thrombotic UK catheter was inserted into the portal vein as an internal shunt bypass (internal shunt group). Similarly, a catheter was inserted between the portal vein and inferior caval vein as an external shunt bypass (external shunt group). The time of portal vein shunt bypass was 2 hrs for both groups. During operations, the blood flow of the hepatic artery was blocked. After the bypass was installed, the hepatic artery and the portal vein were declamped. As a control experiment the hepatic artery was clamped without making a shunt bypass (non-shunt group). Left lateral lobe was resected from the liver prior to the shunt implant and then the right lateral lobe was removed 2 hrs after the declamping of the hepatic artery. Biochemical analysis on mitochondria isolated from the livers of the internal and the external shunt groups was carried out. Changes of mitochondrial ultrastructure were also studied using electron microscope. Changes in serum m-GOT and OCT activities were also examined. Essentially no changes were detected in phosphorylating capacities and ultrastructure of mitochondria of the livers obtained from either the external shunt group or the internal shunt group. However m-GOT and OCT activities in the serum were definitely elevated in the external shunt group of animals compared to those in the internal shunt group of animals. This suggests that the permeability of hepatic mitochondrial membranes in the external group of animals was changed probably due to hypoxia. From these results we recommended the application of the internal shunt bypass for hepato-biliary surgery combined with the resection of the portal vein.     

Hemolytic anemia after ABO nonidentical living donor kidney transplantation

Introduction  ABO compatible non-identical kidney transplants are used frequently. Acquired hemolytic anemia has been reported after ABO mismatched transplantation. Patients of A, B or AB blood groups may receive organs from ABO-compatible, but non-identical donors, mostly from O blood group donors. It may also occur in patients of the AB blood group who receive a kidney from a donor of the A or B blood groups. Patients and methods  ABO non-identical living donor kidney transplantation was done in 214 cases. All studied patients received kidneys from one haplotype HLA mismatched living donors and had pretransplant non-specific blood transfusions. There were 164 males and 50 females with a mean age of 30 years. Ten patients with cyclosporine (CsA)-based therapy developed hemolysis. CsA was stopped in patients maintained on triple immunosuppression (pred, CsA, AZA) and shifted to azathioprine in patients maintained on pred CsA therapy. In all patients pretransplant antibody screen, direct antiglobulin test (DAT) and cytotoxic cross match were all negative. Results  The prognosis was excellent in nine patients, and one died from severe hemolysis. Hemolytic anemia was more frequent among blood group A recipients (60% of our cases) and more severe among recipient blood group B. Six patients received antigen-negative packed RBCs. Univariate analysis demonstrated significant impact for recipient age, donor sex, number of pretransplant blood transfusions, primary immunosuppression, time to onset of diuresis, recipient and donor blood groups. Multivariate analysis restricted the significance to blood group of donor and recipient, time to onset of diuresis and primary immunosuppression. Conclusions  Post transplant hemolysis is infrequent after renal transplantation; however, it may occur with compatible, non-identical ABO blood group donors. Blood group of donor and recipient, time to onset of diuresis and primary immunosuppression (mainly CsA) were significant risk factors in hemolytic anemia in patients after ABO non-identical living donor kidney transplantation. The condition is usually mild and self limited, and change of immunosuppression (stop CsA) can treat the condition.     

Tailored desensitization strategies in ABO blood group antibody incompatible renal transplantation

ABO blood group incompatible renal transplantation, using desensitization procedures, is an effective strategy. Efforts have been made to reduce desensitization: these are usually applied to all patients indiscriminately. The Guy's Hospital ABO blood group incompatible desensitization regimen uses a tiered approach, tailoring strategy according to initial antibody titres. Sixty‐two ABO blood group incompatible living donor transplant recipients were compared with 167 recipients of blood group compatible living donor renal transplants. There were no statistically significant differences in allograft survival rates at 1 or 3 years post‐transplant, rejection in the first year post‐transplant or renal function in the first 3 years post‐transplant. There was a higher rate of death in ABO blood group incompatible transplant recipients – this could be associated with differences in age and HLA mismatch between the two groups. Four ABO blood group incompatible patients experienced antibody‐mediated rejection (no episode was associated with a rise in ABO blood group antibodies). Of the patients who received no desensitization, or rituximab alone, none has experienced antibody mediated rejection or experienced allograft loss. Tailoring the use of desensitization in ABO blood group incompatible renal transplantation according to initial ABO blood group antibody titres led to comparable results to blood group compatible transplantation.     

Portal and arterial washout after hypothermic preservation of the pig liver: prevention of hyperkalaemia after revascularization

In an orthotopic liver transplantation (OLT), portal revascularization may produce acidosis and hyperkalaemia due to loss of intracellular acid metabolites and K+ during hypothermic preservation. To verify the effectiveness of portal and arterial washout in preventing hypokalaemia after liver preservation, an OLT was done in 18 large-white pigs. The donor livers were perfused in situ via the portal vein with Hartmann's solution containing 1.000 IU of heparin at 4 degrees C. Afterwards, a cold Collins C2 solution was perfused either in vitro (group A) or in situ (group B). The cold ischemia time in both groups was less than 3 1/2 h. Before doing the portal revascularization of the donor livers, a washout via the portal vein and hepatic artery with saline serum was performed. The concentration of K+, glucose, GOT and LDH in effluents obtained through infrahepatic inferior vena cava were significantly lower in group B than in group A. Simple washout of the livers prior to revascularization prevented hyperkalaemia in both groups.     

Effects of hypothermic machine perfusion on rat liver function depending on the route of perfusion.

BACKGROUND AND METHODS: The aim of this study was to evaluate the efficacy of hypothermic machine perfusion (HMP) to preserve rat livers according to the route of perfusion, i.e., via portal vein, hepatic veins (retrograde), or hepatic artery. Livers were preserved for 24 or 48 hr by simple cold storage (SCS) or by HMP. Preservation solution was supplemented with (HMP) or without (SCS) hydroxyethyl starch. After preservation, grafts were reperfused for 2 hr with an oxygenated Krebs-Henseleit bicarbonate buffer. RESULTS: After 24 hr of preservation, total glutathione concentrations in HMP livers were similar (1287+/-37, 1418+/-118, and 1471+/-62 nmol/g in hepatic artery, portal vein, and hepatic vein HMP livers, respectively) and higher than in the SCS (833+/-118 nmol/g, P<0.05) group. These higher total glutathione values were due to higher reduced glutathione concentrations. ATP concentrations in the liver tissue were similar in HMP groups (0.75+/-0.4, 0.64+/-0.1, and 0.77+/-0.1 micromol/g in hepatic artery, portal vein, and hepatic vein HMP livers, respectively) and higher than in SCS (0.32+/-0.06 micromol/g, P<0.05). After 2 hr of normothermic reperfusion, bile production in the HMP portal and HMP retrograde groups were similar (391+/-29 ml and 372+/-25 ml) and higher than in the HMP artery or SCS groups (275+/-25 ml and 277+/-32 ml, respectively; P<0.05). Aspartate transaminase, alanine transaminase, lactate dehydrogenase, and purine nucleoside phosphorylase release into the perfusate of HMP portal and HMP retrograde perfused livers was similar and significantly lower compared to the HMP artery and SCS groups. At the end of reperfusion, no statistical differences were found for glutathione concentration and energetic reserves in the livers of each group. After 48 hr of preservation, livers from the HMP portal and HMP retrograde groups did significantly better than livers from the HMP artery or SCS groups. CONCLUSIONS: This study confirms the superiority of HMP over SCS to preserve the liver graft. It shows that retrograde perfusion is similar to PV perfusion and that perfusion by HA is less beneficial.     

Experimental study of partial arterialization of the portal vein on the dearterialized liver

The influence of hepatic arterial obstruction on the hepatic circulation and tissue metabolism was studied between animals with and without partial arterialization of the portal vein. Mongrel dogs were divided into these groups: a group in which the collaterals to the liver were obstructed and the hepatic artery was dissected (hepatic artery ligated group); two groups in which an extracorporeal femoral artery-portal vein shunt was produced, and blood was sent by a Biopump at a rate of 100 or 200 ml/min (100 ml/min and 200 ml/min portal arterialized groups). The hepatic artery ligated group showed CO2 accumulation and acidosis in hepatic venous blood, reduction of oxygen supply, increase of oxygen consumption and marked increase of GOT and GPT. In the portal arterialized groups, sufficient oxygenation of portal blood was noted, and the oxygen demand and supply and tissue metabolism were kept approximately normal. The optimum flow rate for partial arterialization of the portal vein seemed to be 100 ml/min. At the flow rate of 200 ml/min, the original portal blood was reduced, leading to portal hypertension and increase of GOT and GPT. These results indicate that partial arterialization of the portal vein effectively preserves the liver function during the operation and in the early period after dissection of the hepatic artery.