Liver transplantation may prevent neurodevelopmental deterioration in high‐risk patients with urea cycle disorders

UCDs are among the most common inherited metabolic diseases in Japan. We investigated the clinical manifestations, treatment, and prognoses of 177 patients with UCDs who were evaluated and treated from January 1999 to March 2009 in Japan, using a questionnaire survey. Among these 177 patients, 42 (seven with carbamoyl phosphate synthetase 1 deficiency, 27 with ornithine transcarbamylase deficiency, seven with argininosuccinate synthetase deficiency, and one with arginase 1 deficiency) underwent living‐donor LT. Although this study was retrospective and included limited neurodevelopmental information before and after LT, we evaluated whether LT could improve neurodevelopmental outcomes in patients with UCDs. The neurodevelopmental outcomes of patients with a MAC of <300 μmol/L at the time of onset were not significantly different between the LT and non‐LT groups (P=.222). LT may have prevented further neurodevelopmental complications in children with MAC ≥300 μmol/L (P=.008) compared with non‐transplant management. Therefore, Liver transplant should be considered in patients with UCD with a MAC of ≥300 μmol/L at the time of disease onset.     

Tacrolimus‐related seizure after pediatric liver transplantation – A single‐center experience

To identify the risk factors for new‐onset seizures after pediatric LT and to assess their clinical implications and long‐term prognosis. The clinical and laboratory data of 27 consecutive children who underwent LT from January 2007 to December 2010 in our center were analyzed retrospectively. Patients were divided into seizures group and a non‐seizures group. Pre‐operative, intra‐operative, and post‐operative data were collected. Seizures occurred in four children, an incidence of 14.8%. All exhibited generalized tonic–clonic seizures within the first two wk after LT. Univariate analysis showed that the risk factors associated with seizures after pediatric LT included gender, pediatric end‐stage liver disease score before surgery, Child–Pugh score before surgery, serum total bilirubin after surgery, and trough TAC level. Multivariate analysis showed that trough TAC level was the only independent risk factor associated with the seizures. All children who experienced seizures survived with good graft function and remained seizure‐free without anti‐epileptic drugs over a mean follow‐up period of 33.7 ± 14.6 months. High trough TAC level was the predominant factor that contributed to seizures in the early post‐operative period after pediatric LT. High PELD and Child‐Pugh scores before LT and high post‐operative serum Tbil may be contributory risk factors for TAC‐related seizures.     

Intraoperative blood loss and transfusion during primary pediatric liver transplantation: A single‐center experience

Children undergoing liver transplantation are at a significant risk for intraoperative hemorrhage and thrombotic complications, we aim to identify novel risk factors for massive intraoperative blood loss and transfusion in PLT recipients and describe its impact on graft survival and hospital LOS. We reviewed all primary PLTs performed at our institution between September 2007 and September 2016. Data are presented as n (%) or median (interquartile range). EBL was standardized by weight. Massive EBL and MT were defined as greater than the 85th percentile of the cohort. 250 transplantations were performed during the study period. 38 (15%) recipients had massive EBL, and LOS was 31.5 (15‐58) days compared to 11 (7‐21) days among those without massive EBL (P < 0.001). MT median LOS was 34 (14‐59) days compared to 11 (7‐21) days among those without MT (P = 0.001). Upon backward stepwise regression, technical variant graft, operative time, and transfusion of FFP, platelet, and/or cryoprecipitate were significant independent risk factors for massive EBL and MT, while admission from home was a protective factor. Recipient weight was a significant independent risk factor for MT alone. Massive EBL and MT were not statistically significant for overall graft survival. MT was, however, a significant risk factor for 30‐day graft loss. PLT recipients with massive EBL or MT had significantly longer LOS and increased 30‐day graft loss in patients who required MT. We identified longer operative time and technical variant graft were significant independent risk factors for massive EBL and MT, while being admitted from home was a protective factor.     

Outcomes of single kidney transplantation from pediatric donors: A single‐center experience

Kidneys from pDDs are increasingly used to narrow the huge gap between incremental demand and static supply. However, there is still controversy on the clinical outcome of SKT from pDDs. We conducted a retrospective cohort study of 452 adult recipients in our center between March 2012 and February 2017. Outcomes of 3 groups, transplants with organs from pDDs (n=50), aDDs (n=207), and LDs (n=195), were compared. The mean age and weight of pDDs were 8.98 years (range 8 months‐17 years) and 30.05 kg (range 8.2‐55 kg), respectively. There was no difference in 1‐year (96.0%, 98.1%, and 99.0%, respectively, P=.277) and 3‐year patient survival (96.0%, 98.1%, and 99.0%, respectively, P=.277) or in 1‐year (96.0%, 96.6%, and 98.5%, P=.307) and 3‐year (96.0%, 96.6% and 97.9%, P=.437) graft survival. SCr, eGFR, and allograft size were similar among the 3 groups at 6th month post‐transplant and thereafter. Incidence of DGF was higher in patients of the aDD group than those in the pDD group (22.7% vs 10.0%, P<.001), but there was no difference in AR and infection. SKT from pDDs to adult recipients is effective and safe with acceptable outcomes, and it will be a promising expansion to the donor pool.     

Reduced ATG‐F dosage for induction in pediatric renal transplantation: A single‐center experience

Rabbit antithymocyte globulin (ATG‐F) is an extensively used induction agent. To our knowledge, no study to date has assessed reduced ATG‐F dosage in children undergoing renal transplantation. This was a retrospective analysis of pediatric renal recipients in the Department of Kidney Transplantation, The First Affiliated Hospital of Zhengzhou University, from May 2007 to February 2013. Thirty‐nine children underwent renal transplantation including 25 living related and 14 cardiac deceased donor transplantation. Each recipient received ATG‐F 1.5 mg/kg/d once daily for 4 days. Of the 39 recipients, five (12.8%) showed delayed graft function, including one of 25 recipients (4%) of living donor and four of 14 recipients (28.6%) of deceased donor transplantation (p < 0.05). Six of the 39 recipients (15.4%) showed acute rejection on renal biopsy. Follow‐up in these children ranged from 6 to 87 months. The one‐, three‐, and five‐yr recipients and grafts survival rates postoperation were each 94.9% and 97.3%, 97.3%, and 94.6%, respectively. The incidence of postoperative infection was 35.9% (14/39), and did not differ significantly in the living related and deceased donor groups (p > 0.05). Low‐dose ATG‐F can be safely used as an immune induction agent in pediatric renal transplantation.     

Outcomes of pediatric living donor kidney transplantation: A single‐center experience

Renal transplantation is the treatment of choice for children with ESRD offering advantages of improved survival, growth potential, cognitive development, and quality of life. The aim of our study was to compare the outcomes of LDKT vs DDKT performed in children at a single center. Retrospective chart review of pediatric patients who underwent kidney transplantation from 2005 to 2014 was performed. Ninety‐one renal transplants were accomplished, and 31 cases (38.27%) were LDKT, and in 96.7% of the cases, the graft was obtained through laparoscopy. Thirty‐four receptors weighted <25 kg. LDKT group had statistically significant lower cold ischemia times than DDKT one. Complication rate was 9.67% for LDKT and 18.33% for DDKT. eGFR was better in LDKT. Patient survival rate was 100% for LDKT and 98.3% for DDKT, and graft survival rate was 96.7% for LDKT and 88.33%‐80% for DDKT at a year and 5 years. Our program of pediatric kidney transplantation has achieved optimal patient and graft survival rates with low rate of complications. Living donor pediatric kidney transplants have higher patient and better graft survival rates than deceased donor kidney transplants.     

Long‐term outcome of pediatric kidney transplantation: A single‐center experience from Greece

Pediatric kidney Tx has critically altered the outcome in ESRD pediatric patients. The aims of this study were to determine long‐term graft and patient survival in a homogeneous ethnic population. We reviewed the medical charts of pediatric kidney Tx performed between 1990 and 2012 in Greece. Seventy‐five kidney Txs were performed from LRD and 62 from DD. The 10‐ and 20‐yr graft survival was higher in LRD Tx compared with DD Tx. Both patient and graft survival at 10 and 20 yr after Tx were similar in LRD Tx from grandparents compared with parents (92.9% vs. 93.4% 20‐yr patient survival, 71.4% vs. 78.7% and 57.1% vs. 72.1%, 10‐ and 20‐yr graft survival, respectively). However, there was a decreasing tendency in LRD Tx rates in period 2001–2012 compared with period 1990–2000 (47.1% vs. 62.7%). Risk factors for poor five‐yr graft survival were DD Tx, and induction treatment with ALG compared with basiliximab, but their effect attenuated at 10 yr after Tx. In conclusion, Tx from LRD may offer efficient survival outcomes irrespective of donor age, suggesting that even older LRD could be an excellent option for the 1st kidney Tx in children and adolescents.     

Waiting list outcome of Peld/Meld exceptions: A single‐center experience in Argentina

As PELD/MELD‐based allocation policy was adopted in Argentina in 2005, a system of exception points has been in place in order to award increased waitlist priority to those patients whose severity of illness is not captured by the PELD/MELD score. We aimed to investigate the WL outcome of patients with granted PELD/MELD exceptions. A retrospective cohort study was conducted in children under 18 years old. WL outcomes were evaluated using univariable analysis. From 07/2005 to 01/2014, 408 children were listed for LT. There were 304 classified by calculated PELD/MELD. During this time, 85 (30%) PELD/MELD exceptions were granted. In this cohort, 89.4% (76 of 85) were transplanted and 7.1% (6 of 85) died while on the WL. The remaining 3 pts (3.5%) were removed from the WL due to other causes. We compared the impact of PELD/MELD exceptions in those 85 patients to outcomes in 87 non‐exception patients with PELD/MELD ≥19 points. Patients with the exception had significantly better access to WL and lower WL mortality. Our data suggest that children listed by PELD/MELD exceptions had an advantage compared to children with CLD with equivalent PELD/MELD listing priorities.     

Percutaneous interventional management of biliary complications after pediatric liver transplantation: A 16‐year single‐institution experience

The aim of the study was to investigate the BiCx after the pediatric OLT and to assess the efficacy of the fluoroscopic‐guided PBI in the patients with BiCx as compared to the SR. A total of 340 OLTs were performed in 302 patients over the last 16 years. The inclusion criteria were the presence of BS or BL as a complication after OLT. The management of the BiCx was studied. Graft revision, graft loss, and survival were evaluated following PBI and SR. BiCx occurred in 17.1% (58/339) of the transplants; 6.2% (21/339) of transplants demonstrated BL and 12.7% (43/339) of the transplants had BS. Overall graft survival rates at 1 and 3 years in OLT with BL treated with PBI were 75.0% and 68.8% as compared with 75% and 66.7% in OLT treated with SR (P>.05). Overall graft survival rates at 1 and 3 years in OLT with BS treated with PBI were 70.6% and 54.5% as compared with 71.4% and 50% in OLT with SR or ERCP, respectively (P>.05). Based on the results, we conclude that PBI is as effective as SR in patients with the BL and BS after OLT.     

Long‐term outcomes of liver transplantation for hepatoblastoma: A single‐center 14‐year experience

HB is the most common primary liver tumor in children. Complete tumor excision, either by partial resection or by total hepatectomy and liver transplantation, in combination with chemotherapy provides the best chance for cure. We performed a retrospective analysis of patients who underwent liver transplantation for HB and herein present our 14‐year single‐institution experience. Twenty‐five patients underwent liver transplantation for HB at a median age of 26 months (IQR: 15‐44). Graft survival was 96%, 87%, and 80% at 1, 3, and 5 years, respectively. There were four patient deaths, three of them due to disease recurrence within the first year post‐transplant. Ten‐year overall survival was 84%. Three recipients initially presented with pulmonary metastases and underwent resection of metastatic disease, of which two are alive at 3.9 years. Of three patients who underwent salvage transplants, two are alive at 1.5 years after transplant. Non‐survivors were associated with lower median alpha fetoprotein value at presentation compared to survivors (21 707 vs 343 214; P = .04). In conclusion, the overall long‐term outcome of primary liver transplantation for HB is excellent. Tumor recurrence was the highest contributor to mortality. Even patients with completely treated pulmonary metastases prior to transplant demonstrated a favorable survival.     

Hematopoietic stem cell transplantation without in vivo T‐cell depletion for pediatric aplastic anemia: A single‐center experience

For young patients, HLA‐MRD HSCT is the first‐line treatment of SAA. However, due to China's birth control policy, few patients could find suitable sibling donors and HLA‐MUD. More and more transplantation centers have used Haplo‐D as the donor source for young adult and pediatric patients. However, studies with larger amount of pediatric patients are rare. We retrospectively analyzed the data of children with AA who were treated with allogeneic HSCT and compared the therapeutic efficacy of Haplo‐HSCT and MRD/MUD group. A total of 62 patients were enrolled. Implantation was successfully performed in 58 patients. There was no significant difference in the time for reconstruction of hematopoietic function between patients in the two groups. Thirty‐two had grade I‐IV aGVHD with incidence of 51.61%. The incidence of aGVHD was 79.41% for patients in the Haplo‐HSCT, significantly higher than that of 17.86% for patients in the MRD/MUD group (P < .01). However, the incidence of cGVHD was not significantly different between patients in the two groups (26.47% vs 10.71%, P = .09), the incidence of CMV infection was 28.57% and 52.94% for patients in the MRD/MUD and Haplo group, respectively, showing no significant difference (P = .053). The incidence of EBV infection was 47.06% for patients in the Haplo group and 28.57% for patients in the MRD/MUD group, showing no significant difference (P = .11). However, the 3‐ and 5‐year cumulative OS and FFS rates showed statistically significant difference in the two groups, P = .012 and .045, respectively. Compared to Haplo‐HSCT, MRD/MUD is more economic. In this study, we achieved good Haplo transplantation results. The incidences of cGVHD and CMV/EBV were not significantly different between Haplo group and MRD/MUD group. Although OS and FFS of the Haplo group were not as good as those of the MRD/MUD group, it is still acceptable as an alternative treatment under emergency.     

Incidence,impact, and treatment of portal and hepatic venous complications following pediatric liver transplantation: A single‐center 12 year experience

Heffron TG, Pillen T, Smallwood G, Henry S, Sekar S, Casper K, Solis D, Tang W, Fasola C, Romero R. Incidence, impact, and treatment of portal and hepatic venous complications following pediatric liver transplantation: A single‐center 12 year experience.
Pediatr Transplantation 2010: 14:722–729. © 2010 John Wiley & Sons A/S. Abstract: PVT or PVS and HVOO are known causes of graft and patient loss after pediatric liver transplantation. Increased incidences of these complications have been reported in partial livers including DDSLT or LDLT. From 1997 to 2008, 241 consecutive pediatric patients received 271 hepatic grafts at a single center. Median follow‐up is 1856 days. Surgical technique, demographics, lab values, and radiologic imaging procedures were obtained utilizing OTTR^® to evaluate the relationship of portal and hepatic complications with risk factors, patient and graft survival. Grafts were composed of 115/271 (42.4%) partial livers of which 90 (33.2%) were DDSLT and 25 (9.2%) LDLT. Of 271 patients, 156 (57.6%) received whole‐sized grafts. There were six PVC in five patients with one patient requiring retransplantation (0.34%) and no patient deaths. Utilizing all three hepatic vein orifices on the recipient hepatic vena cava and the donor hepatic vein cut short enables a wide hepatic outflow tract unlikely to twist. None of the 241 patients developed early or late complications of the hepatic vein. None of the last 128 consecutive patients who received 144 grafts over seven and a half yr have developed either early or late complications of the hepatic or portal vein. Partial‐graft actuarial survival was similar to whole‐graft survival (87.2% vs. 85.3% at one yr; 76.6% vs. 80.2 at three yr; p = 0.488). Likewise, patient survival was similar between partial grafts and whole grafts (93.8% vs. 93.1% at one yr; 89.8% vs. 87.2% at three yr; p = 0.688) with median follow‐up of 1822 (±1334) days. Patients receiving partial livers were significantly younger and smaller than patients receiving whole livers (p < 0.001). Portal and hepatic venous complications may have negative effects on patient or graft survival after pediatric liver transplantation. In our series, there was one graft and no patient loss related to portal or hepatic venous complications after pediatric liver transplantation over 12 yr.     

Urological complications following kidney transplantation in pediatric age: A single‐center experience

Surgical complications during kidney transplantation can seriously affect renal outcomes. We assess occurrence, risk factors, and results of all urological complications in a series of renal transplants in a single center. Children who underwent renal transplant between January 2008 and December 2014 were retrospectively evaluated. Postoperative urological complications were reviewed. Demographic details, cause of ESRD, donor type, and surgical procedures at transplant were analyzed. For statistical analysis, the chi‐square test or Fisher's exact test were used as appropriate. One hundred and twenty‐one kidney transplants were performed in 117 children (median age 12 yr). Sixty‐two of 121 (53%) had an underlying urological malformation. At a median follow‐up of three yr, 28 urological complications were recorded (23%): 12 lymphocele (10%), 10 ureteral obstruction (8%), three urinary leakage (2.5%), two symptomatic VUR (1.7%), and one hydropyonephrosis. When lymphocele was excluded, the complication incidence rate dropped to 13%. Ureteral obstruction mostly occurred late after transplant (more than six months). Presence of urological malformation was the only factor related to increased occurrence of urological complication (p = 0.007) and, in particular, ureteral obstruction (p = 0.018). Children with urological malformations presented a statistically significant risk of developing urological complications after kidney transplantation, ureteral obstruction being the most common complication.     

Split‐graft liver transplantation from an adult donor with an unrecognized UCD to a pediatric and adult recipient

We report the outcomes of an adult and pediatric split liver transplant from an adult male donor who died due to an unrecognized UCD, OTC deficiency. Recognizing inborn errors of metabolism can be challenging, especially in adult centers where such disorders are rarely encountered. Shortage of donors for liver transplantation has led to procedures to maximize donor utilization, such as split and live donor grafts. The cause of death should be ascertained before accepting a cadaveric donor organ.     

Allogeneic hematopoietic stem cell transplantation in congenital disorders: A single‐center experience

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is the treatment of choice for a variety of congenital disorders. We report the experience of children affected by congenital diseases other than bone marrow failure syndromes who received allo‐HSCT over a period of 25 years at G. Gaslini Paediatric Research Institute. HSCTs were performed in 57 children with congenital diseases (25 with congenital immunodeficiencies, 10 with severe combined immunodeficiencies, and 22 with metabolic diseases). Overall survival rate at 3 years in the whole group of patients was 76.9%, with a trend in favor of better outcome in children with metabolic diseases and in those who received cord blood cells (85.9%) vs bone marrow cells (72.4%).     

Lung transplantation in children following bone marrow transplantation: A multi‐center experience

Allogenic BMT has been successfully performed as a treatment for hematologic diseases with an expected long‐term survival. This survival is truncated by respiratory complications including airway obstruction especially BO. Chronic GVHD has been reported to precede almost all cases reported. LTx has become a therapeutic life‐saving option for patients with end‐stage lung disease that maybe offered for the treatment of GVHD. We report a multi‐center experience of pediatric LTx following BMT in 11 patients age‐ and gender‐matched with 11 controls who received LTx for end‐stage lung disease secondary to CF. Overall death was 36.4% over a follow‐up period of 19 months (range 3–36 months) for the cases and 27.3% for the control group followed for 17 months (range 8–32 months). Median FEV₁ one yr post‐transplant for the cases was 78% predicted compared with 67.3% predicted for the controls. The median for episodes of infection was comparable at a median of one episode per patient through the entire follow‐up period among both groups. Acute rejection episodes were significantly higher in the control group with a median of one episode per patient in the control group compared to none within the cases. Our data suggest that LTx may be a valuable therapeutic option for children with end‐stage lung disease post‐BMT with comparable survival outcome to that after LTx in children for other indications such as CF. Hospital stay was significantly longer in our case group. Infection rate was comparable between groups albeit type of infection varied. Significantly and of interest is that acute rejection episodes were non‐existent in these cases.     

An institutional experience of pre‐emptive liver transplantation for pediatric primary hyperoxaluria type 1

Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disease that culminates in ESRF. Pre‐emptive liver transplantation (pLTx) treats the metabolic defect and avoids the need for kidney transplantation (KTx). An institutional experience of pediatric PH1 LTx is reported and compared to the literature. Between 2004 and 2015, eight children underwent pLTx for PH1. Three underwent pLTx with a median GFR of 40 (30–46) mL/min/1.73 m² and five underwent sequential combined liver‐kidney transplantation (cLKTx); all were on RRT at the time of cLKTx. In one case of pLTx, KTx was required eight and a half yr later. pLTx was performed in older (median 8 vs. 2 yr) and larger children (median 27 vs. 7.75 kg) that had a milder PH1 phenotype. In pediatric PH1, pLTx, ideally, should be performed before renal and extrarenal systemic oxalosis complications have occurred, and pLTx can be used “early” or “late.” Early is when renal function is preserved with the aim to avoid renal replacement. However, in late (GFR < 30 mL/min/1.73 m²), the aim is to stabilize renal function and delay the need for KTx. Ultimately, transplant strategy depends on PH1 phenotype, disease stage, child size, and organ availability.