Long‐Term Outcomes of Pediatric Living Donor Liver Transplantation in Japan: An Analysis of More Than 2200 Cases Listed in the Registry of the Japanese Liver Transplantation Society

The Japanese Liver Transplantation Society (JLTS) was established in 1980 in order to characterize and follow trends in patient characteristics and graft survival among all liver transplant patients in Japan. This study analyzed the comprehensive factors that may influence the outcomes of pediatric patients who undergo living donor liver transplantation (LDLT) by evaluating the largest cohort in the world. Between November 1989 and December 2010, 2224 pediatric patients underwent LDLT in Japan. There were 998 male (44.9%) and 1226 female donors (55.1%) without donor mortalities related to transplant surgery. There were 946 male (42.5%) and 1278 female (57.5%) recipients with a median age of 4.0 years (range: 13 days to 17.9 years). Cholestatic liver disease was the leading indication for LDLT (n = 1649; 76.2%), followed by metabolic disorders (n = 194; 8.7%), acute liver failure (n = 192; 8.6%) and neoplastic liver disease (n = 66; 3.0%). The 1‐, 5‐, 10‐ and 20‐year patient survival rates were 88.3%, 85.4%, 82.8% and 79.6%, respectively. Blood‐type incompatibility, recipient age, etiology of liver disease and transplant era were found to be significant predictors of overall survival. We are able to achieve satisfactory long‐term pediatric patient survival outcomes in the JLTS series without compromising the living donors.     

Portal Vein Complications in Pediatric Living Donor Liver Transplantation Using Left‐Side Grafts

The aim of this report is to assess the rate of portal vein complications (PVCs), the success rate of treatment for PVCs and the prognosis of patients with PVCs for pediatric living donor liver transplantation (LDLT). Pre‐ and postoperative records of 521 pediatric LDLTs, using left‐side grafts were retrospectively reviewed. The overall rate of PVC was 9%, with early PVC occurring in nine patients (1.7%) with a mortality rate of 67% and late PVC in 38 patients (7.3%). Fifteen of these patients with late PVC showed complete portal vein occlusion despite various treatments, and in six of them the graft was lost. Histological examination revealed fibrosis in portal areas in 13 patients, around the central veins associated with cholestasis in the parenchyma in 10, and hepatocyte ballooning in 12. Correction of portal vein flow or retransplantation is necessary for the rescue of patients with early PVCs. Graft loss in the long term may be high with the occurrence of liver failure or portal hypertension related causes, such as hepatopulmonary syndrome and gastrointestinal bleeding in patients with late PVCs. For the rescue of these patients, especially for patients with body weight < 6 kg, regular monitoring of portal vein flow is essential.     

Resource Utilization of Living Donor Versus Deceased Donor Liver Transplantation Is Similar at an Experienced Transplant Center

Although living donor liver transplantation (LDLT) has been shown to decrease waiting-list mortality, little is known of its financial impact relative to deceased donor liver transplantation (DDLT). We performed a retrospective cohort study of the comprehensive resource utilization, using financial charges as a surrogate measure—from the pretransplant through the posttransplant periods—of 489 adult liver transplants (LDLT n = 86; DDLT n = 403) between January 1, 2000, through December 31, 2006, at a single center with substantial experience in LDLT. Baseline characteristics differed between LDLT versus DDLT with regards to age at transplantation (p = 0.02), male gender (p < 0.01), percentage Caucasians (p < 0.01) and transplant model for end-stage liver disease (MELD) score (p < 0.01). In univariate analysis, there was a trend toward decreased total transplant charges with LDLT (p = 0.06), despite increased surgical charges associated with LDLT (p < 0.01). After adjustment for the covariates that were associated with financial charges, there was no significant difference in total transplant charges (p = 0.82). MELD score at transplant was the strongest driver of resource utilization. We conclude that at an experienced transplant center, LDLT imposes a similar overall financial burden than DDLT, despite the increased complexity of living donor surgery and the addition of the costs of the living donor. We speculate that LDLT optimizes transplantation by transplanting healthier and younger recipients.     

Donor‐Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients

With less ischemia, improved donor selection and controlled procedures, living donor liver transplantation (LDLT) might lead to less HLA donor‐specific antibody (DSA) formation or fewer adverse outcomes than deceased donor liver transplantation (DDLT). Using the multicenter A2ALL (Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study) biorepository, we compared the incidence and outcomes of preformed and de novo DSAs between LDLT and DDLT. In total, 129 LDLT and 66 DDLT recipients were identified as having serial samples. The prevalence of preformed and de novo DSAs was not different between DDLT and LDLT recipients (p = 0.93). There was no association between patient survival and the timing (preformed vs. de novo), class (I vs. II) and relative levels of DSA between the groups; however, preformed DSA was associated with higher graft failure only in DDLT recipients (p = 0.01). De novo DSA was associated with graft failure regardless of liver transplant type (p = 0.005) but with rejection only in DDLT (p = 0.0001). On multivariate analysis, DSA was an independent risk factor for graft failure regardless of liver transplant type (p = 0.017, preformed; p = 0.002, de novo). In conclusion, although similar in prevalence, DSA may have more impact in DDLT than LDLT recipients. Although our findings need further validation, future research should more robustly test the effect of donor type and strategies to mitigate the impact of DSA.     

Laparoscopic Versus Open Renal Procurement for Pediatric Recipients of Living Donor Renal Transplantation

Despite reports demonstrating the safety of laparoscopic donor nephrectomy (LDN) for pediatric recipients of renal transplants, recent evidence has challenged using LDN for recipients 5 years of age or younger. We retrospectively reviewed the records of all pediatric recipients of living donor renal transplants from September 2000 through August 2004. We compared those who received allografts recovered by LDN (n = 34) with those recovered by open donor nephrectomy (ODN, n = 26). Outcomes of interest included operative complications, postoperative renal function, the incidence of delayed graft function or episodes of acute rejection and long-term graft function. Donor and recipient demographic data were similar for the LDN and ODN groups. Serum creatinine and calculated creatinine clearance were not significantly different between groups both in the early postoperative period and at long-term follow-up (p > 0.142). Rates of delayed graft function and acute rejection did not differ between groups. Among recipients aged 5 years old or younger stratified by donor technique (9 LDN, 5 ODN recipients), no difference was noted in graft outcomes both early and long-term (p > 0.079). At our center, pediatric LDN recipients have graft outcomes comparable to those of ODN recipients. At experienced centers, we recommend continued use of LDN for pediatric recipients of all ages.     

Active Immunization to Prevent De Novo Hepatitis B Virus Infection in Pediatric Live Donor Liver Recipients

This study aims to evaluate the efficacy of HBV vaccination as an alternative preventive measure against de novo HBV infection in pediatric living donor liver transplantation (LDLT). Sixty recipients were enrolled in this study. Thirty received grafts from anti-HBc(+) donors, and another 30 received grafts from anti-HBc(-) donors. HBV vaccine was given pretransplant to every candidate. Posttransplant, lamivudine was routinely given to recipients receiving anti-HBc(+) grafts for about 2 years. Forty-seven (78%) recipients achieved high levels of anti-HBs titer (>1000 IU/L). Two (3.3%) recipients developed de novo HBV infection where one received an anti-HBc(-) graft and another received an anti-HBc(+) graft. Both recipients were in the lower anti-HBs titer group (<1000 IU/L). The incidence of de novo HBV infection was significantly higher in the lower titer group (15.4% vs. 0%, p = 0.04). The median follow-up period was 51 months in recipients with anti-HBc(-) grafts and 57 months in those with anti-HBc(+) grafts. Active immunization is an effective method to prevent de novo HBV infection. It can result in high levels of anti-HBs titer (>1000 IU/L) which may prevent de novo HBV infection in pediatric patients with efficient primary vaccination undergoing LDLT.     

Is It Right to Promote Living Donor Liver Transplantation for Fulminant Hepatic Failure in Pediatric Recipients?

Good clinical results are currently achieved in elective pediatric liver transplantation (LT) with living-related donors. However, the question whether such therapeutic approach may also be promoted in case of fulminant hepatic failure (FHF) remains a matter of debate. This work briefly reviews the ethical background and overall medical results of living-related donation in pediatric LT. When considering FHF, success is essentially conditioned by the availability of a suitable organ donor before the onset of irreversible brain damage and death of the transplant candidate on the waiting list. Accordingly, living donor LT provides several advantages for patients with FHF, including the short waiting time and the access to a transplant with reduced ischemic injury and optimal graft quality; however, living donation is also characterized by several drawbacks to be carefully considered, particularly the possibility of coercion to the recipient's family as well as the operative risks of the emergency donor hepatectomy. The ethical soundness of living parental donor LT for FHF is discussed, with emphasis to the type of medical context, with or without access to an efficient emergency postmortem organ sharing system.     

Adult Living Donor Versus Deceased Donor Liver Transplantation: A 6-Year Single Center Experience

No long-term (>3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) has been reported. This is a prospective, IRB approved, 6-year comparison of A2ALLTx to ADDLTx. Data include: age, gender, ethnicity, primary liver disease, waiting time, pretransplant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications. In 6 years, 202 ADDLTx (74.5%) and 69 A2ALLTx (25.5%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (48.1% vs. 42%). Data regarding overall patient and graft survival, monetary charges and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (11.5% vs. 23.9%) and more biliary complications (26.1% vs. 11.4%). Overall, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.     

Live Donor Liver Transplantation: A Valid Alternative for Critically Ill Patients Suffering From Acute Liver Failure

We report the outcome of live donor liver transplantation (LDLT) for patients suffering from acute liver failure (ALF). From 2006 to 2013, all patients with ALF who received a LDLT (n = 7) at our institution were compared to all ALF patients receiving a deceased donor liver transplantation (DDLT = 26). Groups were comparable regarding pretransplant ICU stay (DDLT: 1 [0–7] vs. LDLT: 1 days [0–10]; p = 0.38), mechanical ventilation support (DDLT: 69% vs. LDLT: 57%; p = 0.66), inotropic drug requirement (DDLT: 27% vs. LDLT: 43%; p = 0.64) and dialysis (DDLT: 2 vs. LDLT: 0 patients; p = 1). Median evaluation time for live donors was 24 h (18–72 h). LDLT versus DDLT had similar incidence of overall postoperative complications (31% vs. 43%; p = 0.66). No difference was detected between LDLT and DDLT patients regarding 1‐ (DDLT: 92% vs. LDLT: 86%), 3‐ (DDLT: 92% vs. LDLT: 86%), and 5‐ (DDLT: 92% vs. LDLT: 86%) year graft and patient survival (p = 0.63). No severe donor complication (Dindo–Clavien ≥3 b) occurred after live liver donation. ALF is a severe disease with high mortality on liver transplant waiting lists worldwide. Therefore, LDLT is an attractive option since live donor work‐up can be expedited and liver transplantation can be performed within 24 h with excellent short‐ and long‐term outcomes.     

Auxiliary Partial Orthotopic Living Donor Liver Transplantation: Kyoto University Experience

Auxiliary partial orthotopic liver transplantation (APOLT) was initially indicated as a potentially reversible fulminant hepatic failure and non-cirrhotic metabolic liver disease to compensate for enzyme deficiency without complete removal of the native liver. We expand our indication of APOLT for small-for-size grafts to support the function of implanted grafts during the early post-operative period, and for ABO-incompatibility to sustain a patient's life if the patient has a graft failure. We retrospectively reviewed 31 patients undergoing APOLT from living donor. The indication of APOLT was fulminant hepatic failure in 6, non-cirrhotic metabolic liver disease in 6, small-for-size grafts in 13 and ABO-incompatible cases in 6. The cumulative survival rate for APOLT at 1 and 5 years was 57.9% and 50.6%, and 78.8% and 73.8% for standard LDLT. None of the patients who underwent transplantation with APOLT for fulminant hepatic failure had long-term patient survival. The incidence of acute cellular rejection was higher in APOLT (58.1%) than standard LDLT (35.0%). Biliary complication was higher and the need for retransplantation was greater in APOLT than standard LDLT (p < 0.01). The results suggest that the indications of APOLT should be reconsidered in view of the risk for complications and retransplantation.     

Analyses of Peripheral Blood Mononuclear Cells in Operational Tolerance After Pediatric Living Donor Liver Transplantation

Operational tolerance (graft acceptance in an immunosuppression (IS)-free environment) after living-donor liver transplantation (LDLT) could occur by our elective protocol in some patients. There is, nevertheless, no reliable parameter to monitor patients who may discontinue IS without a risk of rejection. To identify such parameters, we systemically phenotyped peripheral blood mononuclear cells from operationally tolerant patients. An increase was observed in the frequency of CD4+CD25high+ cells, B cells and Vdelta1/Vdelta2 gammadeltaT-cells ratio in operationally tolerant patients (Gr-tol; n = 12), compared with those from age-matched volunteers (Gr-vol; n = 24) or patients on IS (Gr-IS; n = 19). The frequency of NK cells was decreased in Gr-tol, compared with those in Gr-IS or Gr-vol. The frequency of NKT cells was decreased after LDLT, compared with that in Gr-vol. Although the contribution of those subsets to the tolerant state remains elusive, the results may provide important clues for reliable indicators of tolerance after LDLT.     

Ischemic Pre-conditioning in Deceased Donor Liver Transplantation: A Prospective Randomized Clinical Trial

To assess the immediate and long-term effects of ischemic preconditioning (IPC) in deceased donor. liver transplantation (LT), we designed a prospective, randomized controlled trial involving 60 donors: control group (CTL, n = 30) or study group (IPC, n = 30). IPC was induced by 10-min hiliar clamping immediately before recovery of organs. Clinical data and blood and liver samples were obtained in the donor and in the recipient for measurements. IPC significantly improved biochemical markers of liver cell function such as uric acid, hyaluronic acid and Hypoxia-Induced Factor-1 alpha (HIF-1 alpha) levels. Moreover, the degree of apoptosis was significantly lower in the IPC group. On clinical basis, IPC significantly improved the serum aspartate aminotransferase (AST) levels and reduced the need for reoperation in the postoperative period. Moreover, the incidence of primary nonfunction (PNF) was lower in the IPC group, but did not achieve statistical significance. We conclude that 10-min IPC protects against I/R injury in deceased donor LT.     

Intraoperative ‘No Go’ Donor Hepatectomies in Living Donor Liver Transplantation

Donor safety is the paramount concern of living donor liver transplantation (LDLT). Although LDLT is employed worldwide, there is little data on rates and causes of ‘no go’ hepatectomies—patients brought to the operating room for possible donor hepatectomy whose procedure was aborted. We performed a single‐center, retrospective review of all patients brought to the operating room for donor hepatectomy between October 2000 and November 2008. Of 257 right lobe donors, the donor operation was aborted in 12 cases (4.7%). The main reasons for stopping the operation were aberrant ductal or vascular anatomy (seven cases), unsuitable liver quality (three cases) or unexpected intraoperative events (two cases). Over the median period of follow‐up of 23 months, there were no long‐term complications of patients with aborted donor procedures. This report focuses exclusively on an important issue: the frequency and causes of no go decisions at a single large volume North American LDLT center. The rate of no go donor hepatectomies should be as low as possible without compromising donor safety—however, even with rigorous preoperative evaluation the rate of donor abortions will be significant. The default surgical position should always be to abort the donor operation if there is an unexpected finding that places the donor at increased risk.     

犬改良背驮式肝移植供肝获取的技术细节

目的介绍犬改良原位背驮式肝移植供肝获取的技术细节。方法回顾性总结24只（包括4只预实验）犬改良原位背驮式肝移植供肝获取的技术细节。结果供肝切除时间平均32（28-36）min,修肝时间平均64（54-70）min。其中,门静脉灌注时间平均11（10-13）min,供肝热缺血时间0 min,冷缺血时间（直至复流前）平均180（152-224）min。获得无肝素的动脉全血300（180-350）ml。病理检查结果：肝细胞轻度水肿,其余无异常。供肝植入10 min后16只即有胆汁分泌,新肝功能良好。结论程序化、标准化获取供肝是犬肝移植获得成功的重要条件,也是保证实验结果可靠、一致的前提。     

亲属活体供肾移植86例近期并发症分析

目的：总结和分析86例亲属活体供肾移植的近期并发症和诊治经验。方法：回顾性分析2003年11月～2009年4月86例亲属活体肾移植的临床资料。其中6例为夫妻间供肾,80例为直系血缘亲属供肾。供体均为开放手术取肾,受体首次移植84例,再次移植2例,术后采用环孢素A（或他克莫司）加霉酚酸酯（或硫唑嘌呤）加泼尼松预防排斥反应。结果：86例供体取肾术后7～10天出院,所有供体随访3～12个月,肾功能正常。86例受者中术后发生急性排斥反应8例,均经甲泼尼龙或抗胸腺细胞球蛋白治疗逆转。6例发生术后肺部感染,死亡2例。4例发生移植肾功能延迟恢复,其中1例并发移植肾周血肿合并弥漫性血管内凝血,最后因多器官功能衰竭死亡。术后移植肾周血肿再次手术6例,5例治愈。发生尿瘘6例,经保守治疗痊愈。83例存活者随访至今,其中术后1年发生慢性移植物失功2例,移植肾功能正常81例。结论：活体亲属供肾移植安全、疗效好,术后应高度重视和正确处理并发症,以获得人肾的长期存活。     

Influence of Graft Type on Outcomes After Pediatric Liver Transplantation

We sought to determine which type of donor graft provides children and young adults with the best outcomes following liver transplantation. Using the US Scientific Registry of Transplant Recipients database, we identified 6467 recipients of first liver transplants during 1989-2000 aged < 30 years. We used Cox models to examine adjusted patient and graft outcomes by age (< 2, 2-10, 11-16, 17-29) and donor graft type (deceased donor full size (DD-F), split (DD-S), living donor (LD)]. For patients aged < 2, LD grafts had a significantly lower risk of graft failure than DD-S (RR = 0.49, p < 0.0001) and DD-F (RR = 0.70, p = 0.02) and lower mortality risk than DD-S (RR = 0.71, p = 0.08) during the first year post-transplant. In contrast, older children exhibited a higher risk of graft loss and a trend toward higher mortality associated with LD transplants. In young adults, DD-S transplants were associated with poor outcomes. Three-year follow up yielded similar graft survival results but no significant differences in mortality risk by graft type within age group. For recipients aged < 2, LD transplants provide superior graft survival than DD-F or DD-S and trend toward better patient survival than DD-S. Living donor is the preferred donor source in the most common pediatric age group (< 2 years) undergoing liver transplantation.     

Rescue of a Living Donor with Liver Transplantation

Postoperative liver failure is a rare complication after living donor liver resection. This is a case report of a 22-year-old healthy donor who was rescued with liver transplantation 11 days after right hemihepatectomy. Nine months later the patient is alive, and has fully recovered from his multiple organ failure. According to a review of the literature, there are four additional living liver donors, who received a liver transplant. Our own patient is the only survivor, so far. This case demonstrates that even in supposedly healthy living donors postoperative complications cannot be completely prevented. Although liver failure is rare in these patients, timely transplantation may need to be considered as the only life-saving treatment.     

Biliary Complications Following Deceased and Living Donor Liver Transplantation: A Review

Introduction

Biliary complications are the most important source of complications after liver transplantation, and an important cause of morbidity and mortality. With the evolution of surgical transplantation techniques, including living donor and split-liver transplants, the complexity of these problems is increasing. Many studies have shown a higher incidence of biliary tract complications in living donor liver transplantation (LDLT) compared with deceased donor liver transplantation (DDLT). This article reviews biliary complications after liver transplantation and correlations with LDLT and DDLT.

Objective

Provide an overview of biliary complications among LDLT and DDLT.

Results

The incidence of biliary complications is higher among LDLT (28.7%) when compared with DDLT (15.5%). Bile leaks were the most common complication due to LDLT (17.1%); however, stricture was the most common complication due to DDLT (7.5%).     

Living Donor Adult Liver Transplantation: A Longitudinal Study of the Donor''s Quality of Life

We report the results of a prospective, longitudinal quality of life survey on our adult right lobe (RL) liver donors. A total of 47 donors were enrolled; a standard SF-36 form and 43 questions developed by our team were completed before donation, at 1 week, and 1, 3, 6 and 12 months after donation. There were no donor deaths. Twenty-nine complications occurred in 16 patients. Major complication rate was 12.8%. Employment status and personal finances were identified as major stressors. All donors who wished to return to work did so by 1 year (mean 3.4 months). Individuals reported between 0 dollars and 25,000 dollars in losses (wages, travel, lodging, etc.). Relationships with recipients and other family members were not altered significantly. Anticipated pain (predonation) was greater than actual pain reported. Donors indicated satisfaction with the donation process regardless of recipient outcome. Physical complaints were significant at 1 week and 1 month, but returned to baseline. Donor mental health remained stable. In conclusion, RL donors found the experience to be a positive one throughout the first postdonation year. The study identified areas (finances, employment and expected recipient outcomes) to be stressed as future donors are evaluated.