Early and late neurological complications of liver transplantation in pediatric patients

NCs occur commonly after solid organ transplantation and affect 15%‐30% of liver transplant recipients. The aim of this retrospective study was to evaluate the type and incidence of neurologic events in pediatric patients following LT. Between May 2006 and June 2015, 242 patients (118 females, 124 males) requiring LT for different etiologies at the ?nönü University Liver Transplantation Institute were included. The incidence, types, and risk factors of NCs that occurred following LT were evaluated retrospectively. Neurologic events occurred in 57 (23.5%) of the patients. Early NCs were encephalopathy (12.4%), seizures (11.5%), and PRES (7%). Of 57 patients, five (8.7%) experienced NCs at least 1 month after LT; these late NCs included tremor, headaches, encephalopathy, ataxia, and neuropathy. The psychiatric symptoms after LT were noted in 42 patients (17.4%). The mortality rate after LT in those with or without neurological events was not significantly different (P=.73). There was a high incidence of serious neurologic events after LT. The major neurologic manifestation in our patients was encephalopathy followed by seizures.     

Vascular complications in living-related and deceased donation pediatric liver transplantation: single center's experience from Turkey

The aim of the study was to assess early and long-term incidence of venous complications, in both deceased donation (DD) and living-related (LR) liver transplantation (LT) in a pediatric population. Seventy-five liver transplants performed in 69 (39 boys, 30 girls) children at Ege University Hospital between 1997 and 2004 were prospectively monitored and reviewed. Age, sex, primary diagnosis, graft type, vascular complications and their management were evaluated. All patients received Doppler ultrasonographic examination both during operation and daily for the first three postoperative days and when necessary thereafter. The complications were classified as early and late presented. Thirty-three grafts (47.8%) were from DD and 36 (52.2%) were from LR donors. Recipients of DD were older than LR donors (mean age 10.5 +/- 5.1 and 5.0 +/- 0.7, respectively) (p < 0.05). Vascular complication occurrence was not statistically different between DDLT and LRLT recipients (p = 0.2), and between infants and children (p = 0.9). Overall, stenosis was more common than thrombosis. We observed hepatic artery (HA) thrombosis, in five of 75 (6.7%) transplants within 30 days post-transplant. Portal vein (PV) thrombosis and hepatic vein (HV) thrombosis were detected in six and one patients (8.7% and 1.3%), respectively. Six PV stenosis were identified (8.7%), while HA and HV-VC (vena cava) stenosis occurred in one and six patients (1.4% and 8.7%), respectively. All PV stenosis (6/33, 18.2%) and one PV aneurysm occurred in DDLT recipients while HV-VC stenosis were detected almost equally in LRLT and DDLT recipients (4/36 vs. 2/33). Except one, all PV stenosis were detected as a late complication and no intervention were needed. Stenosis of HV-VC was more common in girls (5/30 vs. 1/39) (p < 0.05) and the incidence was not different in DDLT and LRLT recipients (p = 0.8). In conclusion, overall incidences of thrombosis and stenosis formation after orthotopic liver transplantation (OLT) were 17.4% and 18.8%, respectively in our center. We suggest that in the cases with HA thrombosis manifested intra-operatively or within the early postoperative period, graft salvage was successful. Thrombosis of HA causes significant mortality. Thrombosis of PV was among the causes of mortality and morbidity. Stenosis of HV-VC could be managed by angioplasty and endovascular stenting with no significant effect to mortality.     

Risk factors for early and late biliary complications in pediatric liver transplantation

BC are a common source of morbidity after pediatric LT. Knowledge about risk factors may help to reduce their incidence. Retrospective analysis of BC in 116 pediatric patients (123 LT) (single institution, 05/1990–12/2011, medium follow‐up 7.9 yr). One‐, five‐, and 10‐yr survival was 91.1%, no patient died of BC. Prevalence and risk factors for anastomotic and intrahepatic BC were examined. There were 29 BC in 123 LT (23.6%), with three main categories: 10 (8.1%) primary anastomotic strictures, eight (6.5%) anastomotic leaks, and three (2.4%) intrahepatic strictures. Significant risk factors for anastomotic leaks were total operation time (increase 1.26‐fold) and early HAT (<30 days post‐LT; increase 5.87‐fold). Risk factor for primary anastomotic stricture was duct‐to‐duct choledochal anastomosis (increase 5.96‐fold when compared to biliary‐enteric anastomosis). Risk factors for intrahepatic strictures were donor age >48 yr (increase 1.09‐fold) and MELD score >30 (increase 1.2‐fold). To avoid morbidity from anastomotic BC in pediatric LT, the preferred biliary anastomosis appears to be biliary‐enteric. Operation time should be kept to a minimum, and HAT must by all means be prevented. Children with a high MELD score or receiving livers from older donors are at increased risk for intrahepatic strictures.     

Infectious complications in pediatric liver transplantation candidates

Cakir M, Arikan C, Akman SA, Baran M, Saz UE, Yagci RV, Zeytunlu M, Kilic M, Aydogdu S. Infectious complications in pediatric liver transplantation candidates.
Pediatr Transplantation 2010: 14: 82–86. © 2009 John Wiley & Sons A/S.
Abstract:  We analyzed infections that occurred within one month prior to LT, identified factors associated with their occurrence and effect of infections on post-transplant mortality. The study group included 40 consecutive children who underwent LT. Sites and types of infection and culture results were recorded prospectively. IID was assessed. Risk factors for the infectious events were analyzed. Forty infection episodes were found in 24 patients (60%); 90% were bacterial, 7.5% fungal, and 2.5% viral. Overall, IID was 38.2 per 1000 patient days. Sites of bacterial infection were urinary tract in 13 events (36.1%) and blood stream in 11 events (30.5%). Bacteremia (culture positive infection episodes) was identified in 19 events (52.7%). Gram-negative isolates were twice as frequent as Gram-positive infections (63.1% vs. 36.9%). Risk factors for the infectious complications were young age, low body weight, prior abdominal surgery, chronic liver disease related to biliary problems, presence of ascites, portal hypertension and cirrhosis, and high PELD score (p < 0.05 for all). Infectious complications in pediatric LT candidates are common. Preventive measures are important not only to reduce the infectious complications but also to prevent the post-operative mortality.     

Posteromedial diaphragmatic hernia following pediatric liver transplantation

Diaphragmatic hernia is a rare complication following pediatric LT. Here, four children who developed right-sided posteromedial diaphragmatic hernias after LT are reported. The primary disease was biliary atresia in two patients, hemangioendothelioma in one, and angiosarcoma in one patient. All of the patients underwent living-donor LT using a left lateral graft. The patients presented with abdominal and/or pulmonary signs and symptoms. The diaphragmatic hernias were diagnosed at 28 days to seven months post-transplant by standard radiographs or chest CT. The defects were located at the posteromedial aspect of the diaphragm and were closed by primary closure. After diaphragm repair, the post-operative course was unremarkable and there were no recurrences. Thermal or mechanical injuries to the bare area, especially in cases of excessive adhesion between the liver and diaphragm after Kasai operation, were the possible causes of the posteromedial diaphragmatic hernia after pediatric LT.     

Early post‐transplant hyperbilirubinemia is a possible predictive factor for developing neurological complications in pediatric living donor liver transplant patients receiving tacrolimus

The cause of post‐transplant CNI‐NCs is multifactorial and not ascribed solely to CNI toxicity. A total of 90 children (aged <20 years) who underwent LDLT were evaluated to investigate the predictive factors associated with CNI‐NCs. Twelve patients (13.3%) developed CNI‐NCs after LDLT (age range, 2‐15 years). The symptoms of CNI‐NCs were seizures, VD, and stupor. The median onset of CNI‐NCs was 10 days (range, 5‐30 days) post‐transplant. In the univariate analysis, higher recipient age at LDLT, donor age and recipient's BW, lower actual GV/SLV and TAC dosage/BW, and higher mean T‐Bil and sodium level for 7 days after transplantation were independently significantly associated with TAC‐NCs. Multivariate analysis showed that the T‐Bil level in the first week after LDLT was the only significant independent predictive factor for TAC‐NCs (HR, 1.588; 95% CI, 1.042‐2.358; P=.031). In conclusion, CNI‐NCs occurred most frequently in children over 5 years and were associated with hyperbilirubinemia for 7 days post‐transplant, regardless of TAC levels. The transplant team should refer to a neurologist to define the diagnosis and to collaborate to resolve the neurological problems.     

Ultrasonography,laboratory, and cholangiography correlation of biliary complications in pediatric liver transplantation

The aim of this study is to correlate the US, laboratory, and cholangiography findings in pediatric liver transplant patients with biliary complications, trying to identify reliable decision‐making tools for the management of these complications. Retrospective review was carried out of US results in 39 consecutive patients, from 2011 to 2013, with biliary complications after LT, documented by PTC. According to US biliary dilation, patients were classified as: mild, moderate, and severe, and according to laboratory findings as: normal or abnormal serum bilirubin and level of serum GGT. Data were correlated with PTC findings, divided in three groups: mild, moderate, and severe/occlusive BDS. There was no statistically significant correlation between the US findings and the laboratory findings and between US findings with PTC. There was a statistically significant correlation between GGT and cholangiography. In our series, abnormal US could not predict the severity of BDS on PTC. Bilirubin results were not able to predict the US findings either. GGT results demonstrated a statistically significant correlation with the severity of BDS found on PTC. These findings emphasize the role of GGT in the evaluation and decision of biliary interventions in pediatric liver transplant recipients.     

Acquired right diaphragmatic hernia following pediatric living donor orthotopic liver transplantation

ADH following OLT is a rare entity. Herein, we report a case of Alagille syndrome who developed ADH secondary to OLT, and possible etiological causes are discussed in light of the literature.     

Tacrolimus-induced cholestatic syndrome following pediatric liver transplantation and steroid-resistant graft rejection

Several factors may contribute to post-transplant cholestatic complications after liver transplantation. These include ischemic reperfusion injury, hypoperfusion, bile duct strictures, and hepatotoxic drugs. Up to now, there have been no publications on tacrolimus cholestatic toxicity in clinical transplantation when the drug was used in therapeutic doses. We describe six pediatric liver graft recipients in whom cholestatic complications developed under a tacrolimus-based immunosuppression following liver transplantation and all of them suffered from previous steroid-resistant graft rejection. The overall incidence of cholestatic syndrome was 5.4% in children receiving tacrolimus. The immunosuppression was switched back to cyclosporine and prednisolone in all six patients resulting in completely resolved clinical signs and laboratory findings. We conclude from our observations that a cholestatic syndrome following pediatric liver transplantation may be caused by tacrolimus therapy following steroid-resistant graft rejection, even if given in therapeutic doses.     

Central pontine myelinolysis following pediatric living donor liver transplantation: A case report and review of literature

CPM is one of the most serious neurological complications that can occur after OLT and is characterized by symmetrical demyelinization in the basis pontis. The etiology of CPM remains unclear, although the rapid correction of the serum sodium and CNI concentrations may be associated with the development of CPM. With recent advances in MRI technology, early diagnosis of CPM has become possible. Here, we present the case of a five‐yr‐old female who developed CNI‐associated CPM after undergoing LDLT. A decreased level of consciousness and dysphasia was noted one wk after LDLT, and MRI revealed findings compatible with a diagnosis of CPM. The patient fully recovered from the neurological deficits related to CPM following the switch from the CNI to sirolimus. We propose MRI to be promptly considered for patients with abnormal neurological findings, together with the substitution of CNI with an mTOR inhibitor as a management regimen for CNI‐related CPM.     

Improved outcomes in pediatric liver transplantation for acute liver failure

Miloh T, Kerkar N, Parkar S, Emre S, Annunziato R, Mendez C, Arnon R, Suchy F, Rodriguez‐Laiz G, Del Rio Martin J, Sturdevant M, Iyer K. Improved outcomes in pediatric liver transplantation for acute liver failure.
Pediatr Transplantation 2010: 14:863–869. © 2010 John Wiley & Sons A/S. Abstract: OLT is a life‐saving option for ALF. Aim: To evaluate our outcomes in pediatric OLT for ALF. Methods: Retrospective review of our data between 1992 and 2007. Results: Of 142 children with ALF, 126 were listed, of which 40 spontaneously improved, nine died, and 77 underwent OLT (median waiting time four days). Fifty‐three children received deceased donor grafts (34 whole and 19 split grafts), and there were 24 living donor grafts. The one‐ and five‐yr patient survival was 87% and 80%, and graft survival 83% and 79%, respectively. Thirteen patients died after OLT, and there were nine retransplants in seven patients. Patient weight, length of stay, creatinine, and infection were significantly associated with death; increased weight and black ethnicity were associated with graft loss on univariate analysis, but not on multivariate analysis. There were no significant differences in patient survival (one and five yr), graft loss, or other complications between the groups. Conclusion: We report the largest single‐center study of OLT in pediatric ALF, demonstrating no difference in outcomes between different graft types. Our liberal use of segmental grafts may allow earlier OLT in this high‐risk cohort and contribute to our excellent outcomes.     

Management of late‐onset portal vein complications in pediatric living‐donor liver transplantation

The purpose of this study was to evaluate retrospectively the results of PTA for late‐onset PV complications after pediatric LDLT and to assess whether a meso‐Rex shunt is a viable option for treating restenosis of the PV after PTA in selected cases. Seventy‐five children who underwent adult‐to‐child LDLT were included in this study, and there were six late‐onset PV complications (8.0%). The initial therapeutic approach was PTA, with or without stent: PTA with balloon dilation for three children, PTA with stent placement for one child, and failure to cannulate the occluded PV for two children. A meso‐Rex shunt was performed in the two children after failed PTA: One suffered complete obstruction of the main PV, and the other, restenosis with total thrombosis after PTA with stent. The PTA was a technical and clinical success in four with PV stenosis of the six patients (66.7%), and successful application of a meso‐Rex shunt in the other two children resulted in restoration of PV flow. In conclusion, PTA is a safe and effective procedure for treating late‐onset PV stenosis after pediatric LDLT. However, in growing pediatric recipients with restenosis of the PV after PTA or chronic PV thrombosis, a meso‐Rex shunt may be a better choice for late‐onset PV complications.     

Pulmonary complications following liver transplantation in pediatric patients

The purpose of this study was to define the incidence and type of pulmonary complications experienced by children after orthotopic liver transplantation (OLT). The radiological records of all patients receiving OLT during a 3-yr period were reviewed to identify evidence of a pulmonary abnormality. Medical records were then reviewed to determine type, duration, therapy and outcome of pulmonary disorders. Potential risk factors for the development of persistent pleural effusions were also analyzed. One hundred and fifty-one pediatric liver transplantations were performed on 113 patients during this period. Pneumonia developed in 27 patients, including 11 proven bacterial, six presumed bacterial, six viral and four fungal cases. All three deaths related to pulmonary complications were in this group. Three patients developed mild pulmonary hemorrhages, and three developed pulmonary calcifications, which did not impair lung function. Sixteen patients developed paralysis of the right hemidiaphragm, four required diaphragm plication. Pleural effusions developed in 86 patients, 38 persisted longer than 7 days. Patients with persistent effusions were more likely to develop allograft rejection than patients with no persistent effusion (p < 0.01) by chi2 analysis. Seven patients required tracheostomy placement. Of these, four were successfully decannulated, two died from non-pulmonary complications and one is receiving home ventilator support. In conclusion, the majority of children experience at least one pulmonary complication after OLT, but mortality due to pulmonary disease is low in this population. Persistent pleural effusions may be a heralding sign of allograft rejection. Viral, bacterial and fungal pneumonia were the only pulmonary causes of death and only one patient in this series has had significant chronic lung disease.     

Risk factors for urological complications following living donor renal transplantation in children

The aim of this study was to detect possible risk factors for UC and UTI following pediatric renal Tx and effect of these complications on outcome. One hundred and eight children who underwent living donor Tx between 2009 and 2015 were retrospectively included. Extraperitoneal approach was used with stented tunneled extravesical procedure. Mean recipient age was 9.89 ± 3.46 years while mean weight was 25.22 ± 10.43 kg. Seventy‐three (67.6%) recipients were boys while 92 (85.2%) were related to donors. Urological causes of ESRD were present in 33 (30.6%) recipients (14 [13%] posterior urethral valve, 16 [14.8%] VUR, and 3 [2.8%] neurogenic bladder). Augmentation ileocystoplasty was performed in 9 (8.3%) patients. Mean follow‐up was 39.3 ± 17.33 months. UC were detected in 10 (9.3%) children (leakage 4 [3.7%], obstruction 3 [2.8%], and VUR 3 [2.8%]) while UTIs were reported in 40 (37%) children. After logistic regression analysis, UC were significantly higher in children with cystoplasty (44.4% vs 6.1%; P = .001). UTIs were significantly higher in girls (51.4% vs 30.1%; P = .001) and in children with urological causes of ESRD (51.5% vs 30.7%; P = .049). UC and UTI were not significantly associated with increased graft loss or mortality. UC were significantly higher in children with cystoplasty while UTIs were significantly higher in girls and children with urological causes of ESRD. Presence of UC did not affect the rate of graft loss or mortality due to its early detection and proper management.     

Non-adherence to medications following pediatric liver transplantation

Non-adherence to medications is a leading cause of organ loss and morbidity in children and adolescents who had a liver transplant. Yet there are very few published studies about ways to detect whether patients are taking their medications or not, and about treatment options to improve adherence. The Pediatric Liver/Liver Transplant Program at Mount Sinai developed clinical and research programs that evaluate adherence. We review initial results from these programs. Clinic patients participate in an adherence-monitoring program that involves standardized assessments by patients, parents, clinicians, and routine examinations of medication blood levels. A research program adds an electronic monitoring device (MEMS-caps, AARDEX/APREX, Switzerland) and examines the use of azathioprine metabolites as predictors for non-adherence. Patients receive a thorough psychosocial evaluation to identify potential risk factors for non-adherence. Preliminary results indicate that an objective adherence detection method has to be incorporated into practice if non-adherence is to be reliably detected (clinicians' impressions and patients' reports are not sufficient). A risk factor for non-adherence, post-traumatic stress disorder, emerges as a potential target for intervention. It is possible to integrate a formal mechanism to assess adherence into the work of a liver/liver transplant clinic. We hope that the presented program will inspire clinicians in the community and other programs to regard the assessment and improvement of adherence to medications as an important goal in the management of children who had a transplant.     

Late airway complications following pediatric liver transplantation: A case series

Background

Late airway complications, as consequence of immunosuppression following pediatric liver transplantation are uncommonly reported.

Methods

In this retrospective case series, we describe two young children presenting with symptoms of airway obstruction, secondary to differing pathologies in the supraglottic airway, as a result of immunosuppression following liver transplantation.

Results

Case 1, a 2-year-old girl who presented with stridor 12-months following liver transplantation, was found to have a proliferative soft tissue mass involving the supraglottic larynx. Biopsies were consistent with infiltrative eosinophilic laryngitis and associated eosinophilic esophagitis. Case 2, a 12-month-old female who presented with stridor 5-months following liver transplantation, was found to have an exophytic soft tissue mass involving the supraglottis and hypopharynx. Biopsies revealed polymorphic Epstein–Barr virus (EBV) driven post-transplant lymphoproliferative disease (PTLD). Case 1 was managed with local resection and high dose oral corticosteroids. Case 2 responded to debulking of the necrotic supraglottic mass, reduction of immunosuppression and rituximab.

Conclusion

A high index of suspicion needs to be maintained for complications of immunosuppression for appropriate diagnosis of airway presentations following pediatric liver transplantation. Further research is necessary to improve early detection and consolidate management strategies for these airway lesions.     

儿童DCD供肝肝移植术后胆道并发症高危因素研究

目的 分析儿童心脏死亡器官捐献(DCD)肝移植受者术后胆道并发症发生的高危因素.方法 收集天津市第一中心医院2013年3月至2015年3月施行的48例儿童DCD肝移植手术的临床资料,回顾性分析临床因素对受者胆道并发症的影响.结果 48例儿童DCD肝移植受者术后共11例发生胆道并发症,发生率为22.9％.单因素分析显示胆道并发症组与对照组间的热缺血时间(P=0.003)差异有统计学意义(P＜0.05),受体年龄(P--0.998)、受体性别(P=0.094)、MELD评分(P=0.159)、PELD评分(P=0.740)、Child-Pugh评分(P=0.159)、冷缺血时间(P=0.990)、受体ICU逗留时间(P=0.105)、是否发生感染(P=0.930)、有无其他并发症(门静脉狭窄/血栓形成、肝动脉栓塞、DGF)(P=0.268)以及A3O血型是否相容(P=1.106)差异无统计学意义(P＞0.05).多因素分析显示热缺血时间(P=0.020,OR=10.367,95％可信区间为1.451～74.089)是术后胆道并发症的独立危险因素.结论 胆道并发症仍然是儿童DCD肝移植术后的重要难题,热缺血时间是受者术后胆道并发症的独立危险因素.因此选择更短热缺血时间的CDC供肝可以降低儿童肝移植受者胆道并发症的发生率.     

Evaluation of renal functions in pediatric liver transplantation

AKI is an important complication after LT. As our LT series contains a quite high number of children with ALF unlike published studies, we aimed to determine pre‐LT and long‐term renal functions in children both with ALF and with CLD. Demographic and disease‐related data of 134 transplanted children were evaluated retrospectively. Pre‐LT and follow‐up GFR and pediatric RIFLE scores were determined. Mean pre‐LT GFR was not dependent on the disease presentation or severity of chronic disease. While there was an initial decline until first week of post‐LT in CLD children, an increase was observed in ALF. Neither mean GFR nor the pRIFLE on follow‐up was different with respect to the type of LT or disease presentation. Mean GFR at first and sixth months were lower in children on cyclosporine compared to tacrolimus (p = 0.001 and p = 0.002, respectively). In conclusion, GFR–time curve was different in children with or without ALF. Type of LT, and severity of the CLD were not risk factors for CKD in any time, but younger age at LT, CLD, and cyclosporine usage were at sixth months of follow‐up.