Marginal donors in liver transplantation

Marginal liver donor criteria included the following: obesity (weight >100 Kg or BMI >27), age >50 years; macrovesicular steatosis >50%; intensive care unit stay >4 days; prolonged hypotensive episodes of >1 hour, and <60 mm Hg with high inotropic drug use (dopamine, [DPM] > 14 microg/kg per minute); cold ischemia time >14 hours, peak serum sodium >155 mEq/L; sepsis, viral infections, and alcoholism; high levels of bilirubin, ALT, and AST, or extrahepatic neoplasia. Between August 1992 and May 2003, we performed 251 liver transplants in 241 patients of whom 155 are presently alive. We used 124 (49.4%) standard donors and 127 (50.6%) marginal donors. Among the group that received a standard donor, 81 (65.3%) are still alive. Among recipients of organs from marginal donors. 81 (63.8%) are still alive. We also assessed the quality of donors according to the severity of recipient disease. For standard donors these outcomes were 61.5% for UNOS 1, 37.5% for UNOS 2A, 73.2% for UNOS 2B, and 80% for UNOS 3 for marginal donors they were 46.1% for UNOS 1, 53.6% for UNOS 2A, 70.7% for UNOS 2B, and 63.6% for UNOS 3. Among the patients who received a liver from a donor >60 years old, there were no survivors in UNOS 1 and 2A, but there were good results in groups 2B and 3. These results suggest there is no difference between marginal and standard donors, even in sick patients, with the exception of donor age.     

活体肝移植供体的安全性

早期活体肝移植主要应用于儿童受体，供肝切取量较小，并发症发生率低，供体安全性很快得到确认。此后，有学者总结了活体肝移植的经验，建立了开展活体肝移植的三条基本原则，即波士顿标准：（1）对于受者具有显著的成功率；（2）对于供者低风险；（3）供者的知情同意。迄今为止，波士顿标准仍然是指导活体肝脏移植开展的基本原则，促使活体肝移植在充分保障供体安全的前提下，逐步应用于成人终末期肝病的治疗。[第一段]     

成人右半肝活体肝移植供者的处理

目的 探讨成人右半肝活体肝移植供者处理的技术问题.方法 对我院2007年4月至2009年2月完成的19例成人右半肝活体肝移植供者资料进行回顾性分析.结果 19例右半肝移植物中带肝中静脉者4例,不带肝中静脉者15例;供肝重量为585～920 g,平均(727.32±117.01)g,与受者标准肝体积比为43%～67%(53.69%±1.77%),与受者重量比为0.82%～1.46%(1.10%±0.04%),供者残肝百分比为32%～55%(47%±2%),供者术中失血量400～1000 ml,平均(660±39.11)ml,输自体血0～735 ml,平均(216.37±62.28)ml,输新鲜冰冻血浆600～2000 ml,平均(789.47±75.66)ml,手术时间480～930min,平均(695.53±26.57)min.供者术后无死亡,发生并发症23例次,按照Clavien分级,Ⅰ级为15例次,Ⅱ级为8例次,经对症处理后均痊愈.住院时间13～58 d,平均(25.42±2.67)d.随访时间6～28月,全部供者均恢复正常工作生活.受者术后1年存活率为78.95%.结论 仔细术前评估,精细手术操作,合理地分配并保证移植物和残肝的功能性体积,术后密切监护、妥善处理并发症是供受者安全的重要保证.     

Donor age in living donor liver transplantation

BACKGROUND: We sought to elucidate the influence of donor age in living donor liver transplantation (LDLT) using either left lobe (LL) or right lobe (RL) grafts. METHODS: Recipients (n = 232) were categorized as: group O/LL (LL, donor age >50, n = 20); group Y/LL (LL, donor age < or =50, n = 140); Group O/RL (RL, donor age >50, n = 12); and group Y/RL (RL, donor age < or =50, n = 61). We compared post-LDLT graft functions. RESULTS: Among LL LDLT, the incidence of small-for-size syndrome was significantly greater for group O/LL compared with group Y/LL (60.0% vs 16.3%, P < .01). However, the cumulative 5-year graft survivals were 73.8% in group O and 76.7% in group Y without substantial difference. In RL LDLT, the post-LDLT morbidity and mortality were similar for group O/RL and group Y/RL. CONCLUSION: Partial liver grafts, even though LL grafts, from older donors can be used safely with caution in LDLT.     

Nonalcoholic steatohepatitis in donors for living donor liver transplantation

BACKGROUND: In 2003, we encountered the first donor death for living donor liver transplantation in Japan, which was related to nonalcoholic steatohepatitis (NASH). The aim of this study was to retrospectively investigate the prevalence of NASH among a living donor liver transplantation donor population and to analyze the postoperative course for both donors and recipients of NASH grafts to minimize risk for donors. METHODS: The study population comprised 263 donors who donated the right lobe of the liver between February 1998 and April 2003. Their zero-hour biopsy specimens were screened retrospectively. Regarding severe steatosis or NASH, long-term follow-up results for laboratory data from donors were investigated along with changes in graft histologic findings in recipients. RESULTS: NASH was diagnosed histopathologically in three cases (1.1%). Pathologic examination showed that a donor who died in 2003 had the most severe NASH among the three cases. The remaining two NASH donors had uneventful postoperative courses without complications. All grafts showed improvement with respect to the steatosis and histologic findings of NASH. CONCLUSIONS: Donor safety is a top priority in living donor liver transplantation. To exclude patients with NASH from potential donor lists, careful evaluation, including selective preoperative liver biopsy, should be carried out.     

Clinical analysis of emergency liver transplantation: the role of living donor liver transplantation

The current liver allocation system requires reevaluation because of the advancements in peri‐transplantation care and surgical techniques. And, the role of living donor liver transplantation (LDLT) in an emergency has not been determined yet. Retrospective review of all patients undergoing emergency liver transplantation (LT) from January 2000 to June 2010 was conducted, and clinical data were analyzed. Of the total 505 LTs, 69 patients (13.7%) underwent an emergency LT. Of these, 54 patients (78.3%) underwent LDLT using a right liver, and 15 patients (21.7%) underwent deceased donor liver transplantation (DDLT). The overall hospital mortality was 21.7% (15/69). The leading cause of death after transplantation was sepsis (60.0%). Multivariate analysis demonstrated that a model for end‐stage liver disease (MELD) >33 [hazard ratio (HR), 16.6; 95% confidence interval (CI), 1.443–191.632; p = 0.024] and existence of pre‐transplantation intubation (HR, 18.2; 95% CI, 1.463–225.483; p = 0.024) were independent factors associated with poor survival after emergency LT. LDLT group and DDLT group showed no difference in hospital mortality (p = 0.854) and graft survival (p = 0.861). Thus, MELD score and respiratory insufficiency could be parameters predicting post‐transplant survival. And, LDLT using the right liver could be an appropriate alternative to DDLT in an emergency.     

The impact of donor age on living donor liver transplantation

BACKGROUND: The impact of the age of the donor on the outcome of living related liver transplantation is yet to be clarified. METHODS: During October 14, 1996 and December 20, 1999, 34 living related liver transplantations were performed. Of these, 26 cases were performed using the extended left lobe graft, which were classified into three groups; younger donor group (group Y, donor age < 30, n = 7), middle-aged donor group (group M, 30 < or = donor age <50, n=13), and older donor group (group O, donor age < 50, n = 6). Early allograft function and regeneration were compared between these groups. RESULTS: There was no difference in standard liver volume, and predicted or harvested graft size between the three groups. Although serum transaminase and total bilirubin levels within postoperative day 7 were not different between the groups, the prothrombin time on postoperative day 3 was significantly longer in group O than in group Y. One week after transplantation, group Y had significantly greater graft/standard liver volume ratio than group O, and greater graft volume than group M and O. One month after transplantation, however, there was no significant difference in such graft size parameters between the groups. Graft and patient survival were comparable between the three groups. CONCLUSION: Although function and regeneration of the allografts from older donors in living donor liver transplantation is worse than those of their younger counterparts, the outcome is not affected by the age of the liver.     

Marginal donors for patients on regular waiting lists for liver transplantation

Abstract  The use of marginal donors is well accepted by most centers for emergency situations, but there is debate on their use for patients on regular waiting lists. We report our experience of the l-year survival for patients on waiting lists ( n = 147, 1-year survival = 32 %), patients transplanted from good donors ( n = 60, l-year survival = 84 %), and patients transplanted from marginal donors (n = 15, l-year survival = 56 %). We concluded that liver transplantation from marginal donors (a) is a safe procedure (b) has a 1 -year survival that is significantly better than that on a waiting list (c) is ethically justified especially in countries with donor shortages, and (d) may allow transplantation of "special" high risk and poor long-term outcome patients.     

Biliary complications among live donors following live donor liver transplantation

Introduction

In live donor liver transplantation (LDLT), bile duct division is a critical step in donor hepatectomy. Biliary complications hence are a feared sequelae even among donors. Long term data on biliary complications in donors from India are sparse.

Quantitative liver function tests in donors and recipients of living donor liver transplantation.

The unique ability of the liver to regenerate quickly after resection makes living donor liver transplantation (LDLT) possible. This technique uses the unique ability of the liver to regenerate to full size after partial resection. However, the quality and course of this regeneration process in humans are still widely unexplored. In the present study we investigated the quantitative liver function tests galactose elimination capacity (GEC), indocyanine green half-life (ICG), and lidocaine half-life as markers for the quality of the liver regeneration in the first 3 months after LDLT. In this study, 22 consecutive living liver donors and their corresponding recipients were analyzed at baseline and at 10 and 90 days after LDLT. Six recipients lost their grafts during the study period. We compared donors and recipients at the different time points. After LDLT, GEC decreased (-42.6%) and ICG increased (+50.6%) significantly in donors. ICG and GEC remained significantly altered over 3 months in donors with an improvement between days 10 and 90 (GEC, +59.3%; ICG, -9.1%). ICG and GEC improved significantly in recipients between days 10 and 90 (ICG, -63.7%; GEC, +16.3%). The lidocaine half-life showed no significant changes. The donors had better test results and recovered faster than the recipients. In conclusion, after LDLT the parameters for liver capacity and flow remain altered in donors and recipients despite rapid volume growth.     

婴幼儿亲属活体部分供肝肝移植中的供、受者安全性分析

目的 探讨婴幼儿亲属活体部分供肝肝移植中的供、受者的安全性.方法 2006年9月至2009年11月,行婴幼儿亲属活体部分供肝肝移植者8例,受者原发病均为先天性胆道闭锁.供者术前常规行三维CT观察和计算全肝及肝叶(段)体积及形状,磁共振胰胆管造影术(MRCP)了解胆道情况.根据婴幼儿受者腹腔容积切取合适肝叶(段)行肝移植术.受者术后给予抗排斥反应和预防感染等治疗;供者术后给予保肝和抑酸治疗.分析供、受者术前、术中及术后情况.结果 8对供、受者手术均获成功.6例供肝为左外侧叶,1例为S3肝段,1例为减体积S3肝段,供肝重量为(235.9±53.6)g(148～302 g),供肝重量与受者体重比(GW/RW)为(2.65±0.48)%(2.11%～3.36%).对供、受者随访3～40个月(中位数18个月),8例供者均存活,发生并发症2例(25%).8例受者中,死亡1例(12.5%),其他受者发生并发症13例次.结论 术前对供、受者行精确评估,切取合适供肝行肝移植术,术中精细操作,术后精心治疗可最大程度保证供、受者的安全.     

Safety of donors in live donor liver transplantation using right lobe grafts

HYPOTHESIS: Right lobe donation was advocated for adult-to-adult live donor liver transplantation but the safety of the donor is still a major concern. We hypothesize that right lobe donation is safe if the lowest limit of volume of liver remnant that can support donor survival is known. DESIGN: Retrospective analysis of data collected prospectively. SETTING: Tertiary hepatobiliary surgery referral center. PATIENTS: Twenty-two live donors involved in adult-to-adult right lobe liver transplantation from May 1996 to June 1999. INTERVENTIONS: The right lobe grafts were obtained by transecting the liver on the left side of the middle hepatic vein. Liver transection was performed by using an ultrasonic dissector, without using the Pringle maneuver. The left lobe volume was measured by computed tomographic volumetry and the ratio of left lobe volume to the total liver volume was calculated. MAIN OUTCOME MEASURES: Hospital mortality rate and complication rate. RESULTS: The median blood loss was 719 mL (range, 200-1,600 mL). Only one donor, who had thalassemia, received 1 U of homologous blood transfusion. Postoperative complications included wound infection, incision hernia, and cholestasis in 1 donor whose liver showed 20% fatty change and who had a left lobe-total liver volume of 0.34. Another donor with 15% fatty change in the liver and a left lobe-total liver volume ratio of 0.27 developed prolonged cholestasis. Two other donors with left lobe-total liver volume ratios of 0.27 but with mild steatosis (<5%) did not develop postoperative cholestasis. Postoperative complications also included 1 case of biliary stricture and 1 case of small bowel obstruction. Both complications were adequately treated. There was no donor mortality. All donors are well and have returned to their previous occupations. CONCLUSION: Live donation of right lobe graft for adult-to-adult liver transplantation is safe provided that the residual liver volume exceeds 30% of the total liver volume and the liver itself is normal or only mildly affected by steatosis.     

The safety of the donor operation in living-donor liver transplantation: an analysis of 45 donors

We retrospectively assessed the safety of the donor operation, based on parameters such as blood loss, blood transfusion, operation time, duration of hospitalization, and complications. Forty-five pediatric and adult recipients underwent living-donor liver transplantation (LDLTx) in Tohoku University Hospital from July 1991 to October 2000. Donor operations were classified into three groups. In the LS group, the graft was the lateral segment ( n=20); in the LL group, the graft was the left lobe without the middle hepatic vein ( n=16); and in the LLM group, the graft was the left lobe with the middle hepatic vein ( n=9). No significant differences were observed among the three groups regarding postoperative liver function or duration of hospitalization. In the LS group, the operation time was shorter and the requirement of autologous blood transfusion was significantly lower than in the other two groups. Most complications following retrieval of the graft were minor. Safety is guaranteed when the left lobe or the left lateral segment is used for LDLTx, but meticulous management of the operation is required to prevent complications.     

Psychosocial data of potential living donors before living donor liver transplantation

In view of the scarcity of organ resources for transplantation, donation by living donors is assuming greater significance now that the technical-surgical problems involved have been solved. In the period between December 1999 and December 2000, 47 potential living liver donors were evaluated and a total of 27 hepatic lobes were transplanted at the Virchow-Klinikum of the Charité Hospital in Berlin. The close personal relationships between recipients and donors gives reason to anticipate high levels of psychosocial pressure during the pre-operative evaluation process; this process consists in part in looking into donor motivation, ambivalence and anxiety. The pre-operative psychometric evaluation of 40 potential living donors indicated that most of the potential donors see themselves as 'super-healthy' and tend to adapt to social expectations, while on the other hand those seven potential living donors not accepted for psychosocial reasons were marked by heightened values for anxious depression and pessimism. The results indicate in most cases a great willingness to donate and on the other hand a high level of obvious psychological pressure for a low number of potential donors. For the latter, both the clinical evaluation interview and the psychometric diagnostics used revealed clear-cut feelings of anxiety and ambivalence towards transplantation.     

Pharmacologic graft protection without donor pretreatment in liver transplantation from non-heart-beating donors

BACKGROUND: Non-heart-beating donors (NHBDs) are considered potential sources of transplant organs in an effort to alleviate the problem of donor shortage in clinical liver transplantation. We investigated the possibility of pharmacologic protection of hepatic allograft function from NHBDs without donor pretreatment. METHODS: Orthotopic liver transplantation was performed using pigs. In donors, cardiac arrest was induced by stopping the respirator. Forty-five minutes after cessation of the respirator, the liver was flushed with cold lactated Ringer's solution including heparin and with the University of Wisconsin (UW) solution, and then preserved for 8 hr at 4 degrees C in the UW solution. The pigs were divided into two groups: a control group and a treated group. In the treated group, an endothelin antagonist TAK-044 was added to the UW solutions (10 mg/L), and TAK-044 (10 mg/kg body weight) and a platelet activating factor antagonist E5880 (0.3 mg/kg body weight) were also administered to the recipients. RESULTS: TAK-044 and E5880 treatment significantly increased the 7-day survival rate of the recipients (100% vs. 17%, P<0.05). In the treated group, portal venous pressure immediately after reperfusion of the graft was significantly lower than in the control group, and postoperative increase in serum concentrations of glutamic oxaloacetic transaminase and total bilirubin was attenuated. Moreover, the energy charge and adenosine triphosphate concentration of the liver were rapidly restored after reperfusion. CONCLUSIONS: Pharmacologic modulation with TAK-044 and E5880 avoiding donor pretreatment can improve the viability of hepatic allografts procured from NHBDs.     

Implication of advanced donor age on the outcome of liver transplantation

Historically, age has been considered to be a relative contraindication for organ donors. The use of elderly donors for liver transplantation remains controversial due to the fear of inferior outcome. According to United Network for Organ Sharing (UNOS) data, the proportion of older donors has been increasing annually. This study describes the short‐ and long‐term outcomes for transplantation of elderly donor livers. Three hundred and seventy‐four primary liver transplantations, which had been performed at the University of Virginia Health System from 7 February 1988 to 31 December 1998, were included. Graft survival, incidence of primary non‐function, and hepatic artery thrombosis (HAT) after transplantation according to the different age groups of liver donors were analyzed. Cases were analyzed by donor age (group I, n=106: aged <20 yr; group II, n=217: aged between 20 and 49 yr; group III, n=51: aged ≥50 yr), and by donor age in comparison with recipient age (group IV, n=65: recipients transplanted with organs from donors within 5 yr of their age; group V, n=266: recipients from donors> 5 yr younger than their age; group VI, n=43: recipients from donors> 5 yr older than their age). Group III or VI (group of advanced donor age) and group II or V (control group) were compared by age, gender, race, body weight, height, pre‐transplantation cytomegalovirus (CMV) status of the recipients donors, cause of brain death of donors, total or warm ischemic time, ABO matching, and degree of human leucocyte antigen (HLA) mismatching. No significant difference in 5 yr graft survival was found between the groups by donor age (p=0.604) and by donor age compared with recipient age (p=0.567). Moreover, no significant differences in the incidence of primary non‐function and HAT after transplantation were found between the groups by donor age and by donor age compared with recipient age. Older donors were more likely to be women and to have antibodies to CMV, as well as to have died by cerebrovascular causes. Race, body weight, height of both recipients and donors, total or warm ischemic time of grafts, ABO matching, and degree of HLA mismatching were not significantly different between the groups. We conclude from this study that advanced donor age is not a contraindication to liver transplantation if careful assessment of donors is made on a case‐by‐case basis. There is a need to maintain an open mind with regard to the use of livers from older donors due to the current situation of serious organ shortages.