Stable long‐term renal function after pediatric liver transplantation

Herlenius G, Hansson S, Krantz M, Olausson M, Kullberg‐Lindh C, Friman S. Stable long‐term renal function after pediatric liver transplantation.
Pediatr Transplantation 2010: 14:409–416. © 2010 John Wiley & Sons A/S. Abstract: Long‐term exposure to calcineurin inhibitors increases the risk of CKD in children after LT. The aims of this study were to study renal function by measuring GFRm before and yearly after LT, to describe the prevalence of CKD (stage III: GFR 30–60 mL/min/1.73 m²) and to investigate if age and underlying liver disease had an impact on long‐term renal function. Thirty‐six patients with a median age of 2.9 years (0.1–16 yr) were studied. Median follow‐up was 6.5 (2–14 yr). GFRm decreased significantly during the first six months post‐transplantation with 23% (p < 0.001). Thereafter renal function stabilized. At six months, 17% (n = 5) of the children presented CKD stage III and at five yr the prevalence of CKD III was 18% in 29 children. However, in 13 children with a 10‐year follow‐up it was 0%. None of the children required renal replacement therapy after LT. When analyzing renal function of those children younger than two yr (n = 14) and older than two yr (n = 17) at the time of transplantation, we found that in both cohorts the filtration rate remained remarkably stable during the five‐yr observational period. However, there was a statistically significant (p < 0.05) difference in the percentual decrease in GFRm between the groups during the first six months after LT 13% and 31%, respectively. Baseline GFRm according to diagnosis did not differ between the groups. During the first six months after LT, patients transplanted for hepatic malignancy (n = 6) and those with metabolic liver disease (n = 4) had a percentage loss of GFRm of 32% and 35%, respectively. The corresponding loss of GFRm in patients with other diseases was 10‐19%. Six months post‐transplantation mean GFRm in the group with malignant liver disease was 65 ± 15 mL/min/1.73 m² and in the group with other diseases (n = 24) 82 ± 17 mL/min/1.73 m² (p < 0.05). At one, three and five yr post‐transplantation there was no longer a statistically significant difference between these cohorts. Our findings suggest that there can be a long‐term recovery of renal function after LT in children.     

儿童肝脏移植术后感染现状分析

自1989年首例儿童活体肝脏移植手术成功以来,肝脏移植术逐渐成为治疗儿童终末期和代谢性肝脏疾病的有效手段.近20年来,随着外科技术的日益完善及免疫抑制剂的合理应用,儿童肝脏移植术后的短期、长期存活率明显提高,但感染仍是肝脏移植术后最常见的并发症,严重影响预后.该文对儿章肝脏移植术后感染现状及合理用药作一概述.     

Development of autoantibodies after pediatric liver transplantation

Dn‐AIH is a long‐term complication after LT. The aim of this study was to analyze the occurrence of autoantibodies in pediatric recipients and the clinical significance. From 1992 to 2008, 96 pediatric LT for non‐autoimmune liver diseases were performed in 94 children in our institution. Serum autoantibodies were checked in 68 subjects (73.9%). A positive autoantibody was defined as titers ≥1:40 for ANA, or ≥1:20 for ASMA, anti‐LKM, and AMA. Autoantibodies were detectable in 51 of 68 patients (75.0%). There was positivity for ANA in 30 patients, ASMA in 32, and AMA in three, while anti‐LKM was all negative. Immunosuppressive treatment with CsA, more than one episode of rejection, and abnormal ALT were risk factors for the development of autoantibodies. The incidence of the development of autoantibodies was 75.0% in pediatric LT cases in this study. ASMA was the most commonly found autoantibody. Autoantibodies may not play a sentinel role for dn‐AIH after LT.     

Oxidative stress after living related liver transplantation subsides with time in pediatric patients

Background

Oxidative stress has been suspected to influence graft survival and prognosis in pediatric recipients of living related liver transplantation (LRLT).

Purpose

We determined the oxidative status of pediatric LRLT recipients during their regular outpatient follow-up visits, and looked for a relationship between oxidative status and post-liver transplantation (post-LTx) duration.

Patients

The study included 43 patients (20 males and 23 females) between the ages of 1.6 and 25.1?years (median 10.7?years) who had undergone LRLT from 5?months to 17.5?years (median 7?years) prior to the study, between the ages of 1.2 and 14.4?years (median 3.5?years).

Methods

Serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), gamma-glutamyl transpeptidase (??-GTP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), direct bilirubin and choline-esterase were measured as part of the patients?? regular follow-up visits. Serum total hydroperoxide (TH) and biological antioxidative potential (BAP) were measured using the free radical analytic system which requires 20???l of serum and 10?min of processing time for each sample. Oxidative stress index (OSI) was calculated as the ratio of TH to BAP.

Results

Serum OSI correlated positively with serum levels of GOT, GPT, LDH, ALP, ??-GTP and direct bilirubin. Serum OSI, TH, LDH, ALP and GOT correlated negatively with post-LTx duration. Serum BAP correlated positively with post-LTx duration. Serum TH correlated positively with serum GOT and ??-GTP, but negatively with serum BAP.

Conclusions

(1) The OSI, which can be calculated based on data acquired through a simple outpatient procedure, can serve as an index of our patients?? laboratory results and oxidative status. (2) The LRLT recipients in our study were at risk for oxidative stress early in the post-operative period, but this risk subsided with time.     

Cognitive and emotional outcome after pediatric liver transplantation

The aim of the study was to evaluate the cognitive and emotional development after pediatric liver transplantation. A total of 21 patients, aged 4-16.9 yr (median 9.6 yr) were tested 1-9 yr (median 4.2 yr) after the transplantation. The pretransplant diagnoses included biliary atresia (eight patients), various metabolic diseases (n = 6), acute liver failure (n = 3), and miscellaneous (n = 4). The cognitive functions were tested with Wechsler preschool and primary scale of intelligence (WPPSI)-R or Wechsler intelligence scale for children (WISC)-III according to age. The Piers-Harris self-concept scale and the evaluation of human figure drawings according to Koppitz were used to detect emotional problems. All tests in all patients were performed by the same psychologist. A significantly lower result on cognitive tests was seen when compared with the expected normal values (p < 0.01). The number of patients with results within or under the lower normal range was higher than expected. Although the mean value of the Piers-Harris self-concept scale was normal, there was a large spread within the group. Indicators of emotional problems were found in the human figure drawings of 50% of the patients. To some extent, low cognitive scores coincided with low scores on self-concept scale and indicators of emotional difficulties. We conclude that the high degree of cognitive and emotional problems after liver transplantation is an important argument for routine psychologic follow-up and support in these patients.     

De novo cholangiocarcinoma after liver transplantation in a pediatric patient

Channabasappa N, Johnson‐Welch S, Mittal N. De novo cholangiocarcinoma after liver transplantation in a pediatric patient
Pediatr Transplantation 2010: 14:E110–E114. © 2009 John Wiley & Sons A/S. Abstract: To date, no child has been reported to develop de novo CCA after liver transplantation although patients with transplants have a significantly higher risk of malignancy than the general population. CCA is extremely rare in the pediatric age group, seen mostly in patients with a history of choledochal cysts, Caroli’s disease, or PSC. We report the first case of pediatric de novo CCA in the liver allograft 12 yr after liver transplantation.     

Outcome of bowel perforation after pediatric liver transplantation

Abstract:  Bowel perforation is one of the causes of mortality after pediatric liver transplantation. The aim of this study was to evaluate the incidence, risk factors, clinical presentations, and outcomes of bowel perforation in pediatric liver recipients. This is a retrospective analysis of all pediatric patients who underwent liver transplantation at a single liver transplant center in Iran between 1999 and 2006. During this period 72 liver transplantations were performed in children <18 yr. Twenty-two children underwent 33 re-explorations after liver transplantation. Five bowel perforations occurred in four children (incidence, 6.9%). One patient required two re-explorations. The median time between liver transplantation and the diagnosis of the bowel perforation was seven days. All patients had abdominal distention before re-exploration. The sites of perforation were jejunum (n = 3) and ileum (n = 2), and simple repair was performed in all cases. Three children had a history of prior Kasai operation. One of them received high dose of methylprednisolone before bowel perforation. Two children expired after bowel perforation (mortality rate, 50%). Bowel perforation is relatively frequent after pediatric liver transplantation. Among risk factors, prior Kasai operation may have a role. We observed that abdominal distention is a sign of bowel perforation and a high index of suspicion is required for rapidly diagnosis of this complication. The outcome of bowel perforation is poor and its mortality is high. Further studies are needed to establish real risk factors for this complication.     

Patterns of infection after pediatric liver transplantation.

OBJECTIVE. To characterize the patterns of infection that occur after orthotopic liver transplantation in children. DESIGN. Inception cohort, retrospective. SETTING. Referral center for liver transplantation, university hospital. PATIENTS. Thirty-six consecutive children who underwent orthotopic liver transplantation and who survived for at least 48 hours after transplantation. INTERVENTIONS. None. MEASUREMENTS AND RESULTS. Twenty-six (72%) of the children had at least one infection, and infection caused four deaths. More infections occurred when prophylactic antilymphocyte antibodies were given than when they were not given (2.9 vs 1.0 infections per transplant). The risk of infection was greatest during the first 2 weeks after orthotopic liver transplantation. Most infections were caused by bacteria (52 cases), followed by viruses (16 cases) and fungi (11 cases). Bacteria were the most common pathogens during all periods, except the third and fourth weeks, when viruses predominated. The most common primary sites of bacterial infection were abdomen (15 cases), bloodstream (15 cases), and surgical wound (10 cases); the most frequent isolates were aerobic gram-negative bacilli (48% of isolates) and enterococci (19%). Cytomegalovirus was the most common viral pathogen (seven cases), and Candida albicans caused all fungal infections. Fungal infections were significantly associated with systemic antibiotic therapy and abdominal complications. CONCLUSIONS. Characteristic patterns of infection occur after pediatric orthotopic liver transplantation, and knowledge of these patterns is likely to result in improved care for transplant recipients.     

Risk factors for impaired quality of life and psychosocial adjustment after pediatric heart,kidney, and liver transplantation

Few studies compare HRQOL and PSA in children who have undergone different types of solid organ Tx. In this cross‐sectional study, HRQOL and PSA were assessed in 74 Tx patients (16 heart, 44 kidney, 14 liver) at a mean age of 11.5 (range 6.3–16.7), 7.2 yr post‐Tx (range 1.0–15.0). HRQOL was self‐assessed using standardized health utility questionnaires (15D–17D). The patients' PSA was evaluated using the Child Behavior Checklist for parents, Youth Self‐Report for patients aged 11–16 yr, and Teacher Report Form. Outcomes did not differ significantly between Tx groups. Preadolescents (8–11 yr) reported poorer HRQOL compared with same‐age peers (p = 0.020). In contrast, adolescents reported similar HRQOL and PSA compared to the general population. Proxy‐reports revealed more PSA problems compared with age expectations (p < 0.01), mainly in internalizing behavior (p < 0.01). Lower HRQOL was associated with shorter follow‐up time since Tx, congenital disease, and a psychiatric or neurological diagnosis. PSA problems were associated with family‐related variables, neurological diagnosis, shorter follow‐up time, and in teacher‐reports longer disease duration before Tx. Different pediatric Tx groups have similar outcome. Neurological comorbidity and shorter follow‐up time are important risk factors, but the impact of family‐related variables on PSA indicate the need of family interventions.     

Real-time and Doppler US after pediatric segmental liver transplantation

BACKGROUND: Accurate diagnosis of hepatic vein (HV) stenosis by real-time and color Doppler US (CD-US) after segmental liver transplantation in children can decrease morbidity because it allows unnecessary biopsy, obstruction or thrombosis and loss of the graft to be avoided. OBJECTIVE: To evaluate CD-US parameters to predict HV stenosis after segmental liver transplantation in children. MATERIALS AND METHODS: Retrospective review of 79 CD-US examinations measuring velocity at the HV anastomosis (HV1) and the main trunk 1-2 cm proximal to the HV/IVC anastomosis (HV2), the HV1/HV2 ratio and the spectral waveform of HV2. The study group comprised patients with stenosis confirmed by angiography. The control group comprised patients with a good clinical outcome. RESULTS: HV stenosis was seen in 12 CD-US examinations. The mean HV1/HV2 ratio was higher in the study group (6.0 versus 4.0). An HV1/HV2 ratio of >4.1 was predictive of HV stenosis (sensitivity 83%, specificity 76%). CONCLUSION: An HV1/HV2 ratio of >4.1 is a highly predictive CD-US parameter for the detection of hemodynamically significant HV stenosis on angiography.     

Vitamin D deficiency and insufficiency after pediatric liver transplantation

Vitamin D deficiency and insufficiency are increasingly recognized in the general population, including healthy children. There is also an increasing emphasis on the importance of vitamin D status following pediatric liver transplantation and specifically its relationship to metabolic bone disease and growth retardation. Vitamin D insufficiency has also been associated with multiple immunological and metabolic disorders in adults. To our knowledge, this has not been systematically evaluated in children undergoing liver transplantation to date. Between October 2004 and August 2008, serum 25‐(OH)‐vitamin D levels were measured in 199 children who had undergone liver transplantation at Birmingham Children's Hospital. Potential factors contributing to vitamin D levels were evaluated. Additionally, we evaluated a possible relationship between vitamin D levels and immunological phenomena and metabolic complications. Median 25‐(OH)‐vitamin D level was 19.5 ng/mL (range: 4.4–71.4 ng/mL). A total of 105 children (53%) had insufficient vitamin D levels and 28 children (14%) showed vitamin D deficiency. The only factors found to be associated with vitamin D deficiency were season of sample, ethnicity, and PTH levels. Vitamin D deficiency was more prevalent during the first year after transplantation. We did not find a significant relationship between vitamin D levels and graft function or any other immunological and metabolic complications. Vitamin D insufficiency and deficiency are common in children after liver transplantation, especially in winter and spring and in non‐white patients. Initial post‐transplant period and high PTH are significantly associated with vitamin D deficiency. Vitamin D status should be monitored following pediatric liver transplantation and vitamin D supplementation provided as required.     

Peripheral eosinophilia and eosinophilic gastroenteritis after pediatric liver transplantation

Reports indicate peripheral eosinophilia (PE) and gastrointestinal eosinophilic inflammation can occur after pediatric liver transplantation. The incidence of these conditions, potential risk factors, and the impact of PE and gastrointestinal eosinophilic inflammation on liver transplant outcome were determined in this pediatric liver transplant program. Medical records of liver transplant recipients from 1 to 97 and from 12 to 99 were reviewed. Fifty-seven transplants on 54 patients were performed during the study period. Fifty-three patients were evaluated; all had normal pre-transplantation peripheral eosinophil counts. PE of > 10% developed in 28% of patients. Using this definition, all such identified patients had absolute eosinophil counts of > 350/mm3. History of immediate hypersensitivity did not differ between patients with or without eosinophilia. Gastrointestinal endoscopy and biopsy was performed in 23 patients with gastrointestinal complaints. Of those, six had eosinophilic gastroenteritis and all six had PE. Compared with patients without eosinophilia, those with PE were younger at the time of transplantation (p < 0.05), had more frequent rejection (p < 0.01), were more commonly managed with tacrolimus-based immunosuppression (p < 0.001), and experienced more frequent episodes of detectable EBV viral load (p < 0.04). Patients with eosinophilic gastroenteritis were more frequently retransplanted (p < 0.006). PE associated with symptomatic eosinophilic gastroenteritis is common after pediatric liver transplantation. Age at transplant, frequency of rejection episodes, tacrolimus-based immunosuppression, and EBV viral load may be associated with the development of this condition. There may be higher rates of graft loss in such patients. Whether innate immune responsiveness or an acquired immune dysregulation accounts for these findings merits further evaluation.     

Real-time and Doppler US after pediatric segmental liver transplantation

Background Accurate diagnosis of portal vein (PV) stenosis by real-time and color Doppler US (CD-US) after segmental liver transplantation in children can decrease morbidity by avoiding unnecessary biopsy, PV hypertension, thrombosis and loss of the graft. Objective To evaluate CD-US parameters for the prediction of PV stenosis after segmental liver transplantation in children. Materials and methods We retrospectively reviewed 61 CD-US examinations measuring the diameter at the PV anastomosis, velocities at the anastomosis (PV1) and in the segment proximal to the anastomosis (PV2), and the PV1/PV2 velocity ratio. The study group comprised patients with stenosis confirmed by angiography and the control group comprised patients with a good clinical outcome. Results PV stenosis was seen in 12 CD-US examinations. The mean PV diameter was smaller in the study group (2.6 mm versus 5.7 mm) and a PV diameter of <3.5 mm was highly predictive of stenosis (sensitivity 100%, specificity 91.8%). Conclusion A PV diameter of <3.5 mm is a highly predictive CD-US parameter for the detection of hemodynamically significant stenosis on angiography.     

Pulmonary complaints and lung function after pediatric kidney transplantation

Abstract:  Recently four of 38 children with a kidney transplant were diagnosed with bronchiectasis. The aim of the current study was to identify patients with increased risk for pulmonary damage. In this cross-sectional observational study, children with a functioning kidney graft in the Netherlands and Antwerp, Belgium, were screened with the use of a symptom checklist and spirometry. Maximum score for upper airway complaints was 21 (normal: <8), for lower airway complaints 28 (<10). Results of FVC, FEV₁ and MEF₂₅ were expressed as percentage predicted for height and sex. One hundred and thirty-five patients completed the interview (122) and/or spirometry (103); 91 did both. Lower airways symptoms were above acceptable levels in 18 (14%) patients. Forty-nine patients (48%) had an abnormal lung function test: in 12 concerning FVC%, in 11 FEV₁%, in 24 MEF₂₅% and in 36 FEV₁/FVC. Of correlations between symptomatology or spirometry data, and clinical parameters, only that between GFR and MEF₂₅% was statistically significant. Children with a kidney transplant are at increased risk for obstructive lung disease. We recommend to monitor lung function during the follow-up after renal transplantation.     

Emotional and behavioral problems after pediatric liver transplantation: a quantitative assessment

Several uncertainties regarding psychological problems in children who underwent liver transplantation and the need to differentiate these disturbances from those related to the underlying previous chronic liver disease itself exist. This background triggered the present pilot study to investigate, using quantitative assessment methods, the incidence and the type of emotional and behavioral disturbances after liver transplantation. Sixteen liver transplant recipients (aged 5.7-14.4 yr) and 12 age-matched controls with stable chronic liver disease were assessed through the parent report form of Child Behavior Checklist/ 4-18. The mean time elapsed since transplantation was 8.1 yr. No patient or family had received psychological support during chronic liver disease or at any phase of the transplantation process. Transplanted children scored within borderline range for Internalizing and Total Behavioral Problems and within pathological range for Competences, except for the Activity Scale. Transplanted children showed more Total Behavioral (p = 0.005) and Externalizing Problems (p = 0.0005) than controls. Both groups scored within the pathological range for Total Competences with no significant differences between the two groups. Our findings suggest that in the absence of support programs a psychological risk does exist for a long period of time, after transplantation. Regarding Total Behavioral Problems and Externalizing Problems, this risk is higher than in children with chronic liver disease.     

Intensive care management after pediatric liver transplantation: a single-center experience

A retrospective study was conducted to determine the significance of intensive care management on outcome after liver transplantation (LTx) in children. Of 195 transplants performed in 162 children, factors affecting morbidity and mortality were documented during the post-operative intensive care unit (ICU) stay. To assess the gain in experience of ICU management, we compared mean ventilation time and stay in the ICU as well as mortality, incidence of surgical complications, infections, and rejection episodes, during three different time-periods (October 1991-August 1994, September 1994-July 1996, and August 1996-February 1998). The time spent by patients in the ICU (9.7 days vs. 7.9 days vs. 4.7 days, p < 0.001) and time on ventilation (5.2 days vs. 3.1 days vs. 1.2 days, p < 0.001) were significantly reduced over the duration of the study. The overall mortality was 18.0% (n = 30) and 76.7% (n = 23) of these deaths occurred during the early post-operative period in the ICU. The incidence of severe surgical complications decreased significantly over time, and the application of intra-operative Doppler ultrasound since 1994 led to detection of 27 correctable vascular complications. The overall incidence of acute cellular rejection episodes in our center was 64.1%: 43.5% of the infectious episodes occurred in the ICU (bacterial 70.2%, viral 12.3%, and fungal 17.5%). The main side-effect from immunosuppressive drugs was arterial hypertension in 29% of the patients. We conclude that our efforts to improve intensive care management and monitoring were the key elements in reducing morbidity and mortality after pediatric LTx.     

Outcome after pediatric liver transplantation impact of living donor transplantation on cost

OBJECTIVE: To compare the direct health care cost of living donor liver transplantation (LDLT) with that of cadaver donor liver transplantation (CDLT) in children and identify predictors of cost. STUDY DESIGN: All 16 children who underwent LDLT from January 1997 through January 2002 at Cincinnati Children's Hospital Medical Center comprised the study population. They were matched for age, diagnosis, and nutritional status with 31 children who received CDLT during the same era. A historic cohort analysis was performed. RESULTS: There was no difference in the 1-year mortality rates between both groups. Costs associated with graft retrieval contributed 15.3% and 31% of the initial transplant cost for LDLT and CDLT, respectively. Mean cost of care in the first year was 60.3% higher for LDLT than CDLT (P=.01). Multivariate analysis identified biliary complications and insurance status as predictors of cost for initial transplantation (R(2)=0.57), whereas biliary complications and pediatric end stage liver disease scores were identified as predictors of cost of care in the first year after transplantation (R(2)=0.77). CONCLUSIONS: The comprehensive cost of LDLT in the first year after transplantation is higher than cadaveric transplantation. This must be balanced against the time spent and care needs of patients on the waiting list.     

Omeprozole therapy in pediatric patients after liver and intestinal transplantation

BACKGROUND: Proton pump inhibitors such as omeprazole are increasingly used to prevent stress-related gastric bleeding in critically ill patients. In this investigation, the acid-suppressive potency of omeprazole was assessed in one at-risk group, pediatric patients undergoing liver or intestinal transplantation, or both. METHODS: Twenty-two patients ranging in age from 0.9 to 108 months (23.8 +/- 6.5) underwent isolated liver (n = 10) or intestinal (11 with composite liver allografts) transplantation. Omeprazole was delivered in bicarbonate suspension through a nasogastric tube. Therapy was started after surgery at 0.5 mg/kg every 12 hours. Gastric pH monitoring was performed approximately 2 days later. RESULTS: For the entire group, mean gastric pH equaled 6.1 +/- 0.3, the same in recipients of isolated liver and intestinal allografts. Twelve of the 22 patients demonstrated a discontinuous omeprazole effect, that is, dissipation of acid reduction before the next dose. Five of the 12 patients with discontinuous omeprazole effect had mean gastric pH of less than 5 (3.9 +/- 0.4). In 4 of these 5, the omeprazole dosing interval was shortened to every 8 or every 6 hours, resulting in an increase in mean pH to 6.6 +/- 0.2 ( P < 0.01). In the remaining 10 of 22 patients, acid suppression was uninterrupted until the next dose. No patient experienced bleeding attributable to gastric erosion. CONCLUSION: Omeprazole suspended in sodium bicarbonate is an effective acid-suppressing agent in pediatric recipients of liver or intestinal transplant, or both. A dosage of 0.5 mg/kg every 12 hours is sufficient for most patients, but dosing every 6 to 8 hours is required to assure maximal acid suppression in all.