Human liver myeloid dendritic cells maturate in vivo into effector DC with a poor allogeneic T-cell stimulatory capacity

We hypothesized that the relatively low immunogenicity of liver grafts might be related to a special maturation program of hepatic myeloid dendritic cells (MDC), yielding relatively immature effector MDC with weak allogeneic T-cell stimulatory capacity. To investigate whether maturation of human liver-derived MDC in vivo differs from maturation of MDC at another anatomical location, we compared the immunophenotypes and allogeneic T-cell stimulatory capacity of MDC from hepatic with those from inguinal lymph nodes (LN). MDC were purified by immunomagnetic selection from hepatic LN obtained from multi-organ donors (n = 8) and from inguinal LN of kidney transplant recipients (n = 7). MDC from hepatic LN had a significantly reduced capacity to stimulate allogeneic T-cell proliferation compared to MDC from inguinal LN. However, this was not due to an immaturity, since MDC from hepatic LN had significantly higher expressions of HLA-DR, CD80, and CD86 compared to MDC from inguinal LN. Hepatic MDC maturate in vivo to a mature type of effector MDC with relatively poor allogeneic T-cell stimulatory capacity.     

Surgical injuries of postmortem donor livers: incidence and impact on outcome after adult liver transplantation.

The exact frequency and clinical consequences of surgical hepatic injuries during organ procurement are unknown. We analyzed the incidence, risk factors, and clinical outcome of surgical injuries in 241 adult liver grafts. Hepatic injuries were categorized as parenchymal, vascular, or biliary. Outcome variables were bleeding complications, hepatic artery thrombosis (HAT), and graft survival. In 82 livers (34%), 96 injuries were detected. Most injuries were minor, but clinically relevant injuries were detected in 6.6% (16/241) of the livers. Fifty (21%) liver grafts had some degree of parenchymal or capsular injury, 40 (17%) had vascular injury, and 6 (2%) had an injury to the bile duct. Procurement region was the only risk factor significantly associated with surgical injury. The rate of hepatic artery injury was significantly higher in livers with aberrant arterial anatomy. Bleeding complications were found in 18% of patients who received livers with a parenchymal or capsular injury in contrast to 9% without parenchymal injury (P = 0.065). HAT was found in 23% of the patients who received a liver with arterial injury compared to 4% without arterial injury (P = 0.001). Overall graft survival rates were not significantly different for grafts with or without anatomical injury. In conclusion, surgical injuries of donor livers are an underestimated problem in liver transplantation and can be observed in about one-third of all cases. Clinically relevant injuries are detected in 6.6% of all liver grafts. Arterial injuries are associated with an increased risk of HAT.     

The hydroxyl radical scavenger MCI-186 protects the liver from experimental cold ischaemia-reperfusion injury

BACKGROUND: Oxidative stress contributes to hepatic ischaemia-reperfusion (IR) injury in a biphasic pattern. In addition to direct cytotoxic effects, oxidative stress also initiates the signal transduction processes that promote second-phase liver injury. The present study investigated the effects of the hydroxyl radical scavenger MCI-186 on the biphasic process of hepatic cold IR injury. METHODS: After cold preservation for 16 h, rat livers were reperfused on an isolated liver perfusion system for 120 min with oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. To determine whether MCI-186 affected cytokine levels that control the second-phase injury, levels of interleukin (IL) 10 and tumour necrosis factor (TNF) alpha were measured in the perfusate. RESULTS: Addition of MCI-186 1 mg/l into the perfusate significantly improved portal flow (P<0.050), hepatic enzyme release into the perfusate (P=0.038), total bile production (P=0.029) and malondialdehyde concentration (P=0.038). Furthermore, treatment with MCI-186 led to a substantial increase in IL-10 release (P=0.032). TNF-alpha levels were not affected. CONCLUSIONS: MCI-186, an agent ready for clinical use, appears to have direct and indirect protective effects against hepatic cold IR injury.     

Preferential induction of Th1 responses by functionally mature hepatic (CD8alpha- and CD8alpha+) dendritic cells: association with conversion from liver transplant tolerance to acute rejection

BACKGROUND: Liver grafts are accepted across major histocompatibility barriers in mice without immunosuppressive therapy. Potentially tolerogenic immature donor dendritic cells (DC) may play a key role in this phenomenon, but recovery of purified DC from normal livers for functional analysis is inherently difficult. Administration of in vitro propagated immature donor DC to recipients of different types of allograft can prolong transplant survival. By contrast, marked increases in donor liver DC as the result of Flt3 ligand (FL) administration and the resulting augmentation of allostimulatory activity within host lymphoid tissue, is associated with acute graft rejection. Here, we compared the capacity of in vitro generated normal liver immature DC and FL-treated donor liver DC to induce alloimmune CD4+ T helper (Th) 1/Th2 and CD8+ T cytotoxic (Tc) 1/Tc2 responses, in vitro and in vivo. METHODS: B10 (H2b, IAb) immature liver DC were propagated from normal hepatic nonparenchymal cells in granulocyte macrophage-colony stimulating factor (GM-CSF) for 6-8 days. Freshly isolated DC from livers of FL-treated mice (FL-liver DC) were cultured overnight (o/n) in GM-CSF, and both myeloid (CD11c+ CD8alpha-) and lymphoid DC (CD11c+ CD8alpha+) flow-sorted for functional analysis. Proliferative activity and production of interferon (IFN)-gamma, interleukin (IL)-4, and IL-10 by naive C3H (H2k, IEk) T cells in response to DC stimulation was assessed by [3H]thymidine incorporation, and by multicolor flow cytometric analysis, respectively, after 3-day mixed leukocyte reactions. To investigate their in vivo trafficking, B10 DC were injected subcutaneously into normal C3H mice. Sections of lymphoid tissue were immunostained for donor MHC class II+ (IAb+) cells, and for IFN-gamma, IL-4, and IL-10 production. Donor cells and clusters of specific cytokine-secreting cells were enumerated. RESULTS: Both in vitro propagated normal liver-derived DC, and freshly isolated bulk FL-liver DC showed an immature phenotype (MHC class II(lo), CD40-, CD80-, and CD86-) and were weak stimulators of naive allogeneic T cells. After o/n incubation in GM-CSF, both CD8alpha- and CD8alpha+ FL-liver DC exhibited marked up-regulation of surface MHC class II and costimulatory molecules, and acquired potent stimulatory activity for Th1 (mainly) and Th2 cells. Both in vitro propagated immature DC and o/n-cultured mature FL-liver DC homed in vivo to host lymphoid tissues, but with different kinetics. Whereas the mature allogeneic FL-liver DC induced IFN-gamma+ clusters in splenic T-cell areas within 2 days, the IFN-gamma response to immature DC was much slower and weaker. CONCLUSIONS: FL-treated donor livers that are rejected acutely contain markedly enhanced numbers of myeloid (CD8alpha-) and lymphoid (CD8alpha+) DC, many of which are capable of maturing rapidly into strong inducers of Th1 and Tcl responses. Substantial differences in quantity, and both the phenotypic and functional characteristics of the DC constituency of donor livers, may contribute significantly toward the distinct outcomes of liver transplant tolerance and rejection.     

An analysis of pretransplantation variables associated with long-term allograft outcome in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy.

BACKGROUND: The present study analyzes pretransplantation variables associated with long-term liver allograft survival in 278 children who underwent transplantation under primary tacrolimus (FK506) therapy at a single center between October 1989 and October 1996. METHODS: The influence of 17 pretransplantation variables on long-term liver allograft outcome was analyzed. Donor variables included age, weight, gender, and cold ischemia time. Recipient variables included age, weight, gender, original liver disease, pretransplantation waiting time, previous abdominal surgery, United Network of Organ Sharing (UNOS) status, ABO blood group, bilirubin level, prothrombin time, ammonia level, creatinine level, and reduced-size/split liver grafts. RESULTS: Overall actuarial graft survival was 79.9% at 1 year, 79.1% at 2 years, and 78.3% at 3, 4, and 5 years. Retransplantation rate was 10.8%. Pretransplantation variables with a significant adverse effect on graft survival by univariate analysis were donor age < or = 1 year (P<0.004), donor weight < or = 10 kg (P<0.003), UNOS status I and II (P<0.007), ABO type O, B, and AB (P<0.03), and reduced-size/split liver grafts (P<0.02). Pretransplantation variables significant by multivariate analysis and therefore independent predictors of inferior graft outcome were donor weight '10 kg (relative risk [RR] 2.91, confidence interval [CI] 1.53-5.51); reduced-size/split liver grafts (RR 2.53, CI 1.30-5.64); and UNOS status I (RR 2.22, CI 1.11-4.43). CONCLUSIONS: Pediatric liver transplant recipients receiving primary tacrolimus therapy have long-term graft survival rates approaching 80%. UNOS status, donor weight, and the use of reduced-size/split liver grafts are the most important factors affecting survival.     

常温机械灌注修复边缘性供肝的临床疗效：单中心报道

目的探讨常温机械灌注（normothermic machine perfusion, NMP）修复边缘性供肝的安全性和有效性。 方法2018年9月至2019年9月,使用NMP进行6例边缘性供肝体外评估和修复,供肝来自4例心死亡和2例高胆红素血症患者。记录灌注过程的灌注参数、灌注液血气分析及生化检验指标,结合供肝外观等评估边缘性供肝是否适合移植。术后随访至少3个月,记录移植后7 d内肝功能指标、生化指标、并发症发生情况等。 结果NMP期间灌注参数稳定,肝动脉灌注流量为110~334 ml/min,门静脉灌注流量为540~1 180 ml/min。灌注液pH、PO₂、PCO₂在灌注0.5 h后基本恢复正常,乳酸水平迅速下降;肝酶水平无明显升高,胆汁pH>7.5。所有供肝灌注均匀,质地柔软,均被用于移植。受者肝移植后恢复情况良好,无一例发生原发性移植肝无功能或缺血性胆道病变,至末次随访所有患者及移植物均存活。 结论本科室在临床肝移植中应用NMP技术的初步经验提示,NMP用于边缘性供肝的保存是安全、有效的。     

Split liver transplantation in Italy

The role of split liver transplantation has been well established. The limitation to this technique is the number of potential recipients for a left lateral segment graft. The optimal use of the donor pool is to split the liver to provide 2 grafts suitable for adults obtaining right or left lobe. We explored the potential increase in the number of liver grafts gained from systematically using the technique of splitting on national basis. The crucial factor appeared to be creation of guidelines for the use of optimal livers to optimize organ allocation while minimizing pretransplantation mortality and maximizing post-orthotopic liver transplantation outcome.     

Survival following liver transplantation from non-heart-beating donors

OBJECTIVE: To determine whether patient and graft survival following transplantation with non-heart-beating donor (NHBD) hepatic allografts is equivalent to heart-beating-donor (HBD) allografts. SUMMARY BACKGROUND DATA: With the growing disparity between the number of patients awaiting liver transplantation and a limited supply of cadaveric organs, there is renewed interest in the use of hepatic allografts from NHBDs. Limited outcome data addressing this issue exist. METHODS: Retrospective evaluation of graft and patient survival among adult recipients of NHBD hepatic allografts compared with recipients of HBD livers between 1993 and 2001 using the United Network of Organ Sharing database. RESULTS: NHBD (N = 144) graft survival was significantly shorter than HBD grafts (N = 26856). One- and 3-year graft survival was 70.2% and 63.3% for NHBD recipients versus 80.4% and 72.1% (P = 0.003 and P = 0.012) for HBD recipients. Recipients of an NHBD graft had a greater incidence of primary nonfunction (11.8 vs. 6.4%, P = 0.008) and retransplantation (13.9% vs. 8.3%, P = 0.04) compared with HBD recipients. Prolonged cold ischemic time and recipient life support were predictors of early graft failure among recipients of NHBD livers. Although differences in patient survival following NHBD versus HBD transplant did not meet statistical significance, a strong trend was evident that likely has relevant clinical implications. CONCLUSIONS: Graft and patient survival is inferior among recipients of NHBD livers. NHBD donors remain an important source of hepatic grafts; however, judicious use is warranted, including minimization of cold ischemia and use in stable recipients.     

Personal experience with the procurement of 132 liver allografts

Abstract. A single donor surgeon's experience procuring the livers from 132 donors is described. Thirty-seven grafts (28. 9%) had hepatic arterial anomalies, 19 (14. 4%) of which required arterial reconstruction prior to transplantation. Of the 121 grafts evaluated for early function, 103 grafts (85. 2%) functioned well, whereas 14 grafts (11. 6%) functioned poorly and 4 grafts (3. 3%) failed to function at all. The variables associated with less than optimal function of the graft consisted of donor age ( P <0. 05), duration of donor's stay in the intensive care unit ( P < 0. 005), abnormal graft appearance ( P < 0. 05), and such recipient problems as vascular thromboses during or immediately following transplantation ( P < 0. 005). A new preservation fluid, University of Wisconsin solution, allowed safe and longer cold storage of the liver allograft than did Euro-Collins' solution ( P < 0. 0001). A parameter of liver allograft viability, which is simple and predictive of allograft function prior to the actual transplant procedure, is urgently needed.     

Dual aortic and portal perfusion at procurement prevents ischaemic‐type biliary lesions in liver transplantation when using octogenarian donors: a retrospective cohort study

Several risk factors for ischaemic‐type biliary lesions (ITBL) after liver transplantation (LT) have been identified, but the role of portal vein perfusion at graft procurement is still unclear. This was a prospective study on double aortic and portal perfusion (DP) of liver grafts stratified by donor's decade (<60 yo; 60–69 yo; 70–79 yo and ≥80 yo) versus similar historical cohorts of primary, adult grafts procured with single aortic perfusion (SP) only. The primary study aim was to assess the role of DP on the incidence of ITBL. There was no difference in the incidence of overall biliary complications according to procurement technique for recipients of grafts <80 years. A higher incidence of ITBL was observed for patients receiving grafts ≥80 years and perfused through the aorta only (1.9 vs. 13.4%; P = 0.008). When analysing octogenarian grafts, donor male gender (HR = 6.4; P = 0.001), haemodynamic instability (HR = 4.9; P = 0.008), and type‐2 diabetes mellitus (DM2) (HR = 3.0; P = 0.03) were all independent risk factors for ITBL, while double perfusion at procurement (HR = 0.1; P = 0.04) and longer donor intensive care unit (ICU) stay (HR = 0.7; P = 0.04) were protective factors. Dual aortic and portal perfusion has the potential to reduce post‐transplant ITBL incidence for recipients of octogenarian donor grafts. Larger series are needed to confirm this preliminary experience.     

Saying "Yes" to obese living liver donors: short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation.

BACKGROUND: The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. METHODS: Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. RESULTS: The treatment significantly improved macrovesicular steatosis (30+/-4% vs. 12+/-2% [mean+/-SEM], P=0.0028). Body weight and BMI were significantly reduced (73.7+/-3.2 kg vs. 66.9+/-2.9 kg, P=0.0033, 26.4+/-0.7 kg/m(2) vs. 24.1+/-0.8 kg/m(2), P=0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n=7) and donor liver without hepatic steatosis (n=37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. CONCLUSIONS: The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.     

Impact of donor gender on male rat recipients of small-for-size liver grafts.

The aim of this study was to assess the impact of donor gender on small-for-size (SFS) liver transplantation in male recipients using a rat model. Adult female or male Lewis rats were used as donors and male Lewis rats as recipients. Size-matched (SM) and SFS liver grafts from either male or female donors were transplanted into male recipients. Animals receiving SFS grafts were sacrificed at postoperative week 1, week 4, and week 12, respectively (n = 6-8 per group), those receiving SM grafts after 3 months. The cumulative survival rate (SVR) in the female-to-male (F-M) SFS group was significantly lower (62%; 13 of 21) compared with the male-to-male (M-M) group (90%; 18 of 20) (P < 0.05). Spontaneous death occurred in the F-M SFS combination either in the early postoperative period (<3 weeks) in animals with confluent hepatic necrosis or in the late postoperative period (>8 weeks) in animals with biliary obstruction. In contrast, no death was observed in the early posttransplantation period after M-M liver transplantation. The relative graft size in the SM F-M group was significantly higher (graft-to-recipient weight ratio [GRWR] 2.40% +/- 0.8%) than in the SFS M-M group (GRWR 1.35% +/- 0.2%; P < 0.001). Regardless of graft size, the outcome was worse in terms of SVR as well as regarding the incidence and severity of biliary complications in F-M compared with M-M liver transplantation. In conclusion, male recipients of female livers had a less favorable outcome irrespective of graft size. Confluent hepatic necrosis as well as biliary obstruction were perceived as consequence of a severe perfusion problem in F-M liver transplantation, which was possibly related to an enhancement of ischemia-reperfusion (I/R) injury by the lack of estrogen in male recipients of female grafts.     

Some functions of canine liver perfused ex vivo with bloodless fluorocarbon emulsion.

6 canine livers were perfused extracorporeally with bloodless fluorocarbon emulsion for 6 h. Perfusate was oxygenated in vitro with a mixture of oxygen and carbon dioxide. Biochemical studies were performed on the samples of perfusate taken from the arterial and venous lines of the perfusion circuit, and of the bile. Hepatic tissue was sampled prior to and following 6 h of perfusion for histological and biochemical studies. Changes, if any, found in the concentrations of various components of perfusate and bile, were considered due to the metabolic activity of the liver. Moderate changes of the liver architecture and a decrease of glycogen were found in hepatic tissues studied microscopically. Under the conditions of the present preliminary experiment, canine livers remained functional after 6 h of perfusion.     

Importance of portal flow diversion in experimental auxiliary partial orthotopic liver transplantation

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has successfully been performed in patients with noncirrhotic metabolic diseases. It remains, however, unclear if intervention in the portal venous inflow is necessary to ensure adequate portal blood flow to graft and host liver. In this experimental study we evaluate the hepatic flow during APOLT. METHODS: Left lateral/medial segmental grafts were transplanted from beagle to dalmatian dogs. Vascular structures were anastomosed end-to-end. The effect of diversion of the portal flow was studied in three groups: in the ligation group (n=3) the host portal vein was tied off, the free flow group (n=6) had random flow to both livers. In the banding group (n=11) the host portal vein was banded with a adjustable strapband to restore the pretransplantation flow distribution. RESULTS: After reperfusion the blood flow through the common portal vein decreased from 49 to 36 ml/kg/min (P<0.03) in all animals. Flow through the left portal vein decreased from 26 to 5 ml/kg/min (P<0.0001). Banding restored the flow in the left portal vein to 12 ml/kg/min, although the flow in the free-flow group remained 4 ml/kg/min. In the ligation group the total portal flow was forced toward the graft leading to the highest perfusion: 24 ml/kg/min (P<0.005). Adverse effect of this ligation was the development of portal hypertension. CONCLUSIONS: This experimental study confirms that diversion of the portal flow is necessary for adequate graft perfusion in APOLT. Banding can restore the pretransplantation flow distribution, without compromising the flow in the common portal vein.     

Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation

BACKGROUND: The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. METHODS: Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. RESULTS: The treatment significantly improved macrovesicular steatosis (30+/-4% vs. 12+/-2% [mean +/- SEM], P = 0.0028). Body weight and BMI were significantly reduced (73.7 +/- 3.2 kg vs. 66.9 +/- 2.9 kg, P = 0.0033, 26.4 +/- 0.7 kg/m vs. 24.1 +/- 0.8 kg/m, P = 0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n = 7) and donor liver without hepatic steotosis (n = 37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. CONCLUSIONS: The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.     

超声对原位劈离式肝移植术前供肝评估价值初探

目的初步探讨超声对原位劈离式肝移植(ISSLT)术前供肝评估的价值。 方法回顾性分析5例脑死亡器官捐献供者接受供肝在体劈离术前的超声检查资料。5例供者术前均行常规二维超声、彩色多普勒超声和剪切波弹性成像检查,酌情行超声造影。 结果常规二维超声显示肝实质回声细小2例,略粗略强2例,增粗增强1例。5例供者肝内动脉、门静脉主干及其属支、肝中静脉及其属支彩色多普勒超声均显示良好。5例供者右肝前叶剪切波成像弹性值为2.67～4.35 kPa。2例供者行超声造影,1例未见异常,1例肝动脉解剖变异。术中所见肝脏血管情况与超声评估相符。病理结果示5例供肝肝小叶结构大致正常,均未见脂肪变性。 结论超声可以作为ISSLT术前供肝评估的首选影像学方法,了解供肝大小、质地、脂肪变性、血管变异等情况,剪切波弹性成像及超声造影从硬度、微循环灌注检测两方面进一步评估供肝质量,作为常规超声的有效补充。     

Donor plasmacytoid dendritic cells modulate effector and regulatory T cell responses in mouse spontaneous liver transplant tolerance

We assessed the role of donor liver non-conventional plasmacytoid dendritic cells (pDCs) in spontaneous liver transplant tolerance in a fully MHC-mismatched (C57BL/6 (H2^b) to C3H (H2^k)) mouse model. Compared with spleen pDCs, liver pDCs expressed higher levels of DNAX-activating protein of 12 kDa and its co-receptor, triggering receptor expressed by myeloid cells 2, and higher ratios of programed death ligand-1 (PD-L1):costimulatory CD80/CD86 in the steady state and after Toll-like receptor 9 ligation. Moreover, liver pDCs potently suppressed allogeneic CD4⁺ and CD8⁺ T cell proliferative responses. Survival of pDC-depleted livers was much poorer (median survival time: 25 days) than that of either untreated donor livers or pDC-depleted syngeneic donor livers that survived indefinitely. Numbers of forkhead box p3 (FoxP3)⁺ regulatory T cells in grafts and mesenteric lymph nodes of mice given pDC-depleted allogeneic livers were reduced significantly compared with those in recipients of untreated livers. Graft-infiltrating CD8⁺ T cells with an exhausted phenotype (programed cell death protein 1⁺, T cell immunoglobulin and mucin domain-containing protein 3⁺) were also reduced in recipients of pDC-depleted livers. PD1-PD-L1 pathway blockade reversed the reduction in exhausted T cells. These novel observations link immunoregulatory functions of liver interstitial pDCs, alloreactive T cell exhaustion, and spontaneous liver transplant tolerance.     

Older liver graft transplantation, cholestasis and synthetic graft function

Older liver grafts are often discarded because of conservative selection criteria. We report on our clinical experience with graft-age related outcome. Patients transplanted with livers older than 70 years (70.2-80.2 years, n = 38) were compared with controls transplanted with livers younger than 70 years. Pairs were matched for age, gender, indication and cold ischemic time. Mean donor age was 73.4 +/- 2 vs. 39 +/- 16 years. Patient and graft survival did not differ between both groups after 1-year follow-up (P = 0.19 and P = 0.24 respectively). Retransplantation rate was 10.5% vs. 5.3% (P = 0.40). Initial poor function occurred in two patients in the study group versus four patients in the control group (P = 0.69). The incidence of rejection episodes was comparable. Parameters of cholestasis and protein synthesis showed no difference 1-year post-transplant. Mean age of donor organs in matched pairs group B was near by half of that in the older donor group A (39.0 vs. 73.4 years). Post-transplant outcome as indicated by patient and graft survival was comparable between both groups. Donor organ age had no impact on postoperative organ function. We recommend to accept liver grafts from organ donors older than 70 years to expand the donor pool.     

改进成人间活体供肝移植的手术技术

目的研究并改进成人间活体供肝移植的手术技术。方法自2002年1月至2005年8月,施行了16例成人间活体右半供肝移植。手术中改进了技术,包括右肝静脉重建、肝中静脉分支搭桥、肝动脉搭桥及胆道吻合等。结果所有供者均无严重并发症及死亡。移植肝与受者重量比（GRWR）为0．72％～1．24％,其中9例〈1．0％,2例〈0．8％。手术除了采用移植肝的右肝静脉与受者下腔静脉（IVC）直接吻合外,5例加行右肝下静脉重建、5例取自体大隐静脉行肝中静脉分支与IVC间搭桥,保证了右肝流出道通畅。最早手术的2例受者中,1例发生肝静脉吻合口狭窄,另1例发生小肝综合征,最终导致死亡。后阶段手术的14例受者均未发生小肝综合征;发生并发症5例,分别为急性排斥反应、肝动脉栓塞、胆漏、左膈下脓肿及肺部感染;1例再次肝移植后因肺部感染,多器官功能衰竭（MOF）死亡。结论活体供肝移植中采用改进的手术技术,特别是肝静脉流出道重建的方法,可有效避免发生小肝综合征。     

Liver transplantation using suboptimal grafts: impact of donor harvesting technique.

In recent years, an increasing number of suboptimal grafts has been used to reduce the gap between the supply and demand of organs for liver transplantation (LT). In this randomized prospective study, we tested the impact of donor harvesting technique on the posttransplantation outcome of suboptimal donor livers. A modified double perfusion (MDP) technique (aortic and portal cooling with tourniquet clamping of splenomesenteric vein inflow) was compared with the single aortic perfusion (SAP) technique. Between February and November 2005, 35 suboptimal grafts were randomly assigned to either technique (18 MDP livers and 17 SAP livers). Donor and recipient variables were comparable in the 2 study groups. The SAP group had significantly higher blood transaminases and bilirubin levels after LT. The prevalence of graft primary dysfunction (PDF) was also significantly higher (P=0.01) in the SAP group (35%) than in the MDP group (5%). In 5 cases, all in the SAP group (P=0.02), early re-LT (<30 days) was needed. The 6-month patient and graft survival rates were significantly higher in the MDP (100% in both cases) than in the SAP group (68% and 58%, respectively). The study was stopped in November 2005, when the interim analysis revealed such markedly significant differences between the two groups. In conclusion, the present study showed a very low prevalence of PDF, death, and re-LT after transplantation with suboptimal liver when a MDP technique was used to harvest the donor graft.