Post-transplant food allergy in children is associated with liver and not with renal transplantation: A monocentric comparative study

Food allergy is increasingly reported after paediatric liver transplantation. The underlying physiopathological mechanism remains incompletely understood. Therefore, we aimed to determine the incidence, clinical presentation, possible risk factors, and prognosis of post-transplant food allergy in children currently followed after liver and renal transplantation. The study population consists of 49 liver and 21 renal transplant patients transplanted between the age of 22 months and 15 years. Data were collected retrospectively from medical records and via a doctor’s questionnaire taken from the parents in a monocentric setting. Post-transplant food allergy has developed in 13 liver transplant patients and in none of the renal transplant recipients. Within the liver transplant group, median age at liver transplantation is significantly lower in the food-allergic (10 months) versus non-food-allergic group (3.3 years; p?=?0.002). The use of tacrolimus as primary maintenance immunosuppression is associated with food allergy (p?=?0.032) and mean donor age is significantly lower in the food-allergic group (p?=?0.009). Compared to the renal transplant group, median age at transplantation is significantly lower in the liver patients (p?<?0.001). No significant differences are found in primary immunosuppressive regimens between renal and liver transplant patients. Conclusion: Post-transplant food allergy is an important clinical problem in children after liver transplantation which does not affect renal transplant patients despite similar immunosuppressive regimens. Within the group of liver transplant recipients, tacrolimus use, young age at time of transplant and younger donor age were associated with the development of food allergy.     

肝移植术后完全停用免疫抑制剂三例儿童临床特点分析

目的 探讨肝移植术后完全停用免疫抑制剂儿童的临床特征,寻找可能与术后免疫耐受形成有关的因素.方法 回顾性分析我院2008年7月至2009年6月间完成的儿童肝移植中完全停用免疫抑制剂的3例患儿资料,包括:移植年龄、原发疾病、供肝来源、术后免疫抑制剂、随访检查结果等.结果 3例完全停药儿童的原发病均为胆道闭锁,平均移植年龄7个月17 d,均为母体活体供肝肝移植,肝移植术后免疫抑制剂方案均为强的松龙+环孢素A,服药至少2年以上,完全停药1年以上.结论 移植年龄＜1岁、原发病为胆道闭锁、母体供肝、服药2年以上、服用环孢素A是这些完全停药儿童的共同特征.     

Post-transplant diabetes mellitus in children following renal transplantation

Abstract:  PTDM plays a role in chronic allograft nephropathy and decreases graft and patient survival. Considering the serious outcome of chronic hyperglycemia, the importance of early recognition and the few data in children, in this retrospective analysis we studied the characteristics and risk factors of PTDM in 45 pediatric renal transplant recipients receiving Tac or CyA-based immunosuppression. Fasting blood sampling and OGTT were performed. PTDM has been developed in six patients (13%), while seven children (16%) had IGT, with the overall incidence of a glucose metabolic disorder of 29% in pediatric renal transplants. Patients in the PTDM + IGT group were younger and had higher systolic blood pressure and serum triglyceride level than children with normal glucose tolerance. Multivariate analysis identified Tac treatment, Tac trough level, steroid pulse therapy and family history of diabetes to be associated with the onset of PTDM. In pediatric renal transplants, OGTT and frequent assessment of blood glucose levels might be essential not only in the post-transplant management, but also prior to transplantation, particularly with family history of diabetes. Careful monitoring and modified protocols help to minimize the side effects of Tac and corticosteroids.     

Risk of hearing impairment in pediatric liver transplant recipients: a single center study

As survival rates following liver transplantation have increased, health care providers must assess the impact of transplantation on dimensions other than traditional medical measures. Hearing impairment may adversely impact social, emotional, cognitive, academic, and speech and language development. We hypothesized that children who undergo liver transplantation are at risk for hearing impairment due to exposure to ototoxic drugs. We conducted a review of 74 children who had undergone liver transplantation between December 1996 and September 2000 at Cincinnati Children's Hospital Medical Center. Hearing was assessed at discharge by an audiologist using age and developmentally appropriate techniques. The principal outcome measure was sensorineural hearing impairment. Independent variables were age at transplantation, United Network for Organ Sharing (UNOS) status at transplantation, primary diagnosis, post-transplant length of hospital stay, days of treatment with aminoglycosides, and days of treatment with loop diuretics. Eleven of 74 children (15%) had sensorineural hearing loss, of whom four had severe to profound hearing loss. Multivariate analyses showed that the adjusted relative risk for hearing loss in patients with hepatoblastoma was 66 and that there was a 5% increase risk for hearing loss for each additional day of hospitalization. Age at transplantation, UNOS status, and days of treatment with loop diuretics or aminoglycosides did not achieve significance in the model. Sensorineural hearing impairment occurs in a subset of pediatric patients following liver transplantation. Patients with hepatoblastoma or those who experience prolonged hospitalization after transplantation are at increased risk. Our observations are of particular importance for pediatric liver transplant recipients since the median age at transplantation is 12-18 months, a critical period for language acquisition.     

Vaccination status in pediatric liver transplant candidates

Abstract:  Infection is a recognized and potentially serious complication in children following solid organ transplantation. This problem is particularly important for young children undergoing any organ transplantation who often have not completed standard childhood immunizations at the time of transplantation and who are therefore at risk for vaccine-preventable infections. To evaluate the vaccination status in liver transplant candidates, vaccination charts of 100 patients who were referred to Organ Transplant Center of Nemazee Hospital were reviewed and the vaccination status considered appropriate according to the recommendation of NIP and the patients' age. Fifty-eight percent of patients were completely vaccinated for HBV, 85% for OPV, 97% for BCG, 63% for DTP, and 58% of the patients were completely vaccinated for MMR. We concluded that the vaccination charts should be periodically reviewed and updated to prevent the vaccine-preventable disease in liver transplant candidates not only before but also after transplant. Every effort should be made to assure that candidates are immunized early in the course of their disease. Also it may be indicated to recommend a special guideline for immunization of liver transplant candidates and add other vaccines such as Haemophilus influenzae and Streptococcus pneumoniae vaccine to their vaccination program.     

Jejunal varices diagnosed by capsule endoscopy in patients with post‐liver transplant portal hypertension

Portal hypertension secondary to portal vein obstruction following liver transplant occurs in 5%‐10% of children. Jejunal varices are uncommon in this group. We present a case series of children with significant GI blood loss, negative upper endoscopy, and jejunal varices detected by CE. Case series of patients who had CE for chronic GI blood loss following liver transplantation. Three patients who had their initial transplants at a median age of 7 months were identified at our institution presenting at a median age of 8 years (range 7‐16 years) with a median Hgb of 2.8 g/dL (range 1.8‐6.8 g/dL). Upper endoscopy was negative for significant esophageal varices, gastric varices, and bleeding portal gastropathy in all three children. All three patients had significant jejunal varices noted on CE in mid‐jejunum. Jejunal varices were described as large prominent bluish vessels underneath visualized mucosa, one with evidence of recent bleeding. The results led to venoplasty of the portal vein in two patients and a decompressive shunt in one patient with resolution of GI bleed and anemia. CE is useful to diagnose intestinal varices in children with portal hypertension and GI bleeding following liver transplant.     

Impact of liver transplantation on HRQOL in children less than 5 years old

Our primary goal was to assess health related quality of life (HRQOL) at transplantation and 1 yr after transplantation in pediatric liver transplant patients aged less than 5 years. We conducted a prospective longitudinal study of HRQOL in pediatric liver transplant recipients, aged less than 5 years to define the impact of liver transplantation on HRQOL and identify factors that predict HRQOL after transplantation. The infant toddler health status questionnaire (ITHQ) was completed at the time of listing for liver transplantation and at 6 and 12 months after liver transplantation. The primary outcome measures were the subscale scores that comprise ITHQ. The mean age (+/-s.e.m.) of the enrolled patients (n = 45) at transplantation was 1.4 (+/-1.2) yr. Thirty-eight (84%) of the enrolled patients completed the study. The highest mean baseline scores of 78.6 (+/-3.3) were for global mental health (GlobalMH). ITHQ subscale scores increased steadily after transplantation. The greatest increase was in the first 6 months after transplant. At 1 yr after transplantation, there were significant increases in all of the ITHQ subscale scores except for GlobalMH. ITHQ subscales were similar for patients who received LDLT compared with those who received cadaver donor liver transplantation (CDLT) at baseline and a year after transplant. Time elapsed as transplantation was a significant predictor of functional health in all of the models generated. Scores for general health (GH), global health (GGH), parental time-impact (PT) and parental time-emotion (PE) were higher for male children. Family cohesion (FC) improved with time elapsed since transplant and increased number of inpatient days. HRQOL improves after transplantation in all of our patients irrespective of the donor type. Functional health scores were higher in patients with normal serum bilirubin at 1 yr post-transplant. Assessment of HRQOL should be an integral part of care for liver transplant patients and their caregivers.     

Investigation of impaired carbohydrate metabolism in pediatric liver transplant recipients

Abstract:  OGTT was performed in 28 liver transplants maintained with tacrolimus to investigate carbohydrate metabolism and assess risk factors for development of PTDM. None had PTDM that was detected by OGTT. Early PTDM in four cases (14.3%) resolved in follow-up. Five new cases (17.9%) demonstrated DCM (DCM  = IGT ± hyperinsulinemia). Fasting measurements were normal in two hyperinsulinemic cases. With one (20%, p > 0.05) exception none of the children with DCM were overweight or had a family history of diabetes. All five (100%) children with DCM had been given high cumulative dosage of steroids 18 (78.3%) – without DCM (p > 0.05). The median age of children with DCM was greater [4.3 (12.7–18.0) vs. 7.0 (2.3–18.0) yr, p < 0.01] and duration of follow-up longer [5.3 (2.3–7.0) vs. 2.5 (0.7–7.3) yr, p < 0.05]. Four children (80%) with DCM were pubertal (p < 0.05). However, neither age nor duration of follow-up or pubertal stage had significant effect on DCM development. Early PTDM is a transient phenomenon and is not predictive for future development of diabetes. DCM is frequently observed in liver transplanted children. Albeit the children with DCM were given high cumulative dose of steroids, were older, mostly were pubertal, and had longer duration of follow-up, we cannot draw firm conclusions on effects of the risk factors on carbohydrate metabolism because of the small sample size and relatively short duration of follow-up. Unlike fasting measurements, OGTT can detect all children with DCM.     

The impact of public health service increased risk donors in pediatric liver transplantation

Many transplant programs are reluctant to use organs from deceased donors designated as “PHS increased risk” due to misconceptions regarding the quality of those organs. This study evaluated the impact of PHS increased risk donors on patient and allograft survival in pediatric patients undergoing liver transplantation. Retrospective analysis of the UNOS database from January 2005 through September 2017 revealed 5615 pediatric patients who underwent isolated liver transplantation; of these, 5057 patients received primary isolated liver transplants and 558 patients received isolated liver retransplants. PHS increased risk organs were used in 6.7% and 5.4% of the children receiving primary isolated and retransplant livers, respectively. Cox proportional hazards models adjusted for donor and recipient characteristics determined the relative risk of PHS status on allograft and patient survival. Sicker children (those in ICU [P < .001] and on life support [P = .04]) were more likely to receive PHS increased risk donor organs. There were no differences in overall patient (P = .61) or allograft (P = .68) survival between pediatric patients receiving PHS positive vs PHS negative deceased donor organs; adjusted models also demonstrated no statistically significant differences in patient or allograft survival. Excellent patient and allograft survival can be accomplished with PHS increased risk organs.     

Long-term follow-up of portal hypertension after liver transplantation in children

Abstract:  We aimed to describe the long-term changes in the imaging and clinical features of PHALT in children. A retrospective review was undertaken of consecutive children undergoing their first liver transplant between 1993 and 2003. Details of clinical progress and ultrasound imaging were recorded at one-yr post-transplantation and at last follow-up. Data were extracted on 83 children (median age at transplant 1.7 yr, range one month to 17.5 yr, 44 girls) who underwent 89 transplants. Four of these children died at a mean 5.6 yr (range 3.8–6.9 yr) after transplantation. Of the survivors, follow-up at one yr (n = 83) and at last follow-up (n = 71, median 4.3 yr post-transplant) revealed imaging evidence of splenomegaly in 46% and 44%, ascites in 6% and 4%, and portal systemic collaterals in 12% and 14%, respectively. Gastrointestinal hemorrhage associated with portal hypertension had occurred in no children at one yr and in four (6%) at latest follow-up. Features of portal hypertension on ultrasound scan are common in children before liver transplantation. An important minority of children will suffer clinically significant complications of PHALT during long-term follow-up, caused by both vascular and parenchymal disease.     

Graft reduction in pediatric hepatic transplantation: value, technique and results]

The benefit of liver transplantation in children with end-stage liver disease is now well established. A few years ago, the scarcity of suitable pediatric donors was responsible for death in 30 to 50% of children on the waiting list and most of them died before the age of 3 years. Since 1981, the use of reduced-size graft in pediatric liver transplantation allowed a dramatic decrease of the pretransplant mortality rate which is now 2 to 14%. The choice of the reduction technique is based on two parameters; the first one is the donor recipient body weight ratio, the second one is the intra-operative measurement of the recipient's internal transverse basithoracic distance. Nowadays, 30 to 50% of the children undergoing a liver transplant, receive a reduced-size graft. The results of reduced-size orthotopic liver transplantation are comparable with full-size orthotopic liver transplantation; the one-year survival rate is 70 to 85%. These results justify the continued use of reduced-size liver transplantation in children with end-stage liver disease. Transplantation of two patients with one liver (bipartition) and liver transplantation from living related donor, which represents an improvement of the reduction technique, was recently performed successfully and may become a useful concept in pediatric liver transplantation.     

New-onset diabetes mellitus presenting with diabetic ketoacidosis after pediatric liver transplantation

Abstract:  The development of NODM is a common metabolic complication after liver transplantation. Presentation of post-liver transplant diabetes mellitus with DKA is rare especially among pediatric patients. We reported three pediatric patients who presented with DKA after liver transplantation. The underlying diseases leading to transplantation were cryptogenic liver cirrhosis, Wilson disease, and congenital hepatic fibrosis. None of the three patients had a history of diabetes prior to transplantation and all of them were cases of NODM after transplantation. All three patients presented with severe hyperglycemia, significant ketosis, and metabolic acidosis of variable severity. All of them received tacrolimus as one of the immunosuppressant agents. The patients received a liver transplant from a DD. The patients were treated with intravenous insulin injection (0.1 U/kg/h) and recovered from DKA, but one case expired in the intensive care unit because of bacterial sepsis after recovery from DKA. Our experience suggests that PTDM may result in ketoacidosis, and we emphasize the importance of paying more attention to glucose metabolism and risk of diabetes mellitus in patients with immunosuppressive therapy, especially tacrolimus.     

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.     

Rapid discontinuation of corticosteroids in pediatric renal transplantation

Abstract:  Corticosteroid immunosuppression has permitted the development of successful allotransplantation; however, corticosteroids are associated significant post-transplant complications. To circumvent these problems, we implemented a protocol of rapid discontinuation of corticosteroids in 19 consecutive pediatric primary kidney transplant recipients. Mean age at time of transplant was 13.4 (±4.5) yr, 52.6% were male, 63.2% underwent living donor transplantation. All patients were administered Thymoglobulin^® [anti-thymocyte globulin (rabbit)] as induction immunosuppression with a rapid tapering dose of corticosteroids (total of five daily doses), and maintained on mycophenolate mofetil and tacrolimus. Two patients had immediate recurrence of primary disease (FSGS), requiring further corticosteroid therapy. Otherwise, remaining 17 patients were maintained off corticosteroids, with excellent graft function; mean baseline eGFR of 112 mL/min/1.73 m² (±19) at 28 months (±14) post-transplantation. There was 100% patient and rejection-free graft survival at 27 months (range 5–58 months) post-transplantation; 47% underwent renal transplant biopsy secondary to acute rise in serum creatinine with or without worsening hypertension. All biopsies had no evidence of acute rejection; 62.5% had findings consistent with tacrolimus toxicity. Renal transplantation utilizing a rapid discontinuation of corticosteroid protocol in pediatric patients appears to be safe and effective, without increasing the risk of acute rejection or graft loss.     

Predictors of cardiac allograft vasculopathy in pediatric heart transplant recipients

CAV remains a leading cause of late graft loss and mortality among survivors of pediatric heart transplantation. We sought to define the incidence of CAV and identify its predictors in pediatric heart transplant recipients. The OPTN/UNOS database was analyzed for pediatric recipients who underwent heart transplant between 1987 and 2011. The primary end‐point is time from heart transplantation to development of CAV (CAV‐free survival). To identify predictors of CAV‐free survival, demographic and transplant data were analyzed by the Kaplan–Meier survival method and Cox proportional hazards regression. Of 5211 pediatric heart transplant recipients with at least one‐yr follow‐up, the incidence of CAV at five, 10, and 15 yr was 13%, 25%, and 54%, respectively. Multivariate analysis found that risk of CAV was associated with the following variables: Recipient age 1–4 yr (HR 1.25), 5–9 yr (1.45), 10–18 yr (1.83), donor age >18 yr (1.34), re‐transplantation (2.14), recipient black race (1.55), and donor cigarette use (1.54). Older recipient and donor age, recipient black race, donor cigarette use, and re‐transplantation were highly associated with shorter CAV‐free survival.     

Audit of eosinophilic oesophagitis in children post-liver transplant

Abstract:  Pediatric liver transplantation has proven so successful that 10-yr survival post-transplantation is in excess of 70% and following transplantation, emphasis of medical care switches from life saving to promotion of good quality of life. EE is an increasingly recognised phenomenon in the general population. Eosinophilic disorders of the GI tract are increasingly recognised in patient's post-solid organ transplantation but the contribution of EE to morbidity in this population has not been addressed to date. The objective of this study was to identify the incidence of EE in children receiving liver transplantation by the QLTS over the last 15.5 yr. Comprehensive review of medical records of all liver transplant recipients during study period via cross-checking procedural and electronic laboratory results was performed. All oesophageal biopsies reporting mucosal inflammation were reviewed. EE can be diagnosed when oesophageal biopsy reveals ≥5 eosinophils per HPF; however, we used a cut-off of 20 eosinophils per HPF, which is in accordance with current opinion. In the 159 children who received DD OLT, 130 survived and four have been diagnosed with EE (3%). Only 34 are currently followed in Queensland and all four patients diagnosed are in this cohort representing 12% of our follow-up clinic. Many patients are followed elsewhere so occurrence of EE in our total surviving population is an underestimate. EE is clinically important in the post-liver transplant community. Children post-OLT who have upper GI symptoms should be considered for endoscopic evaluation and biopsy to exclude EE.     

Post‐transplant glucose status in 61 pediatric renal transplant recipients: Preliminary results of five Turkish pediatric nephrology centers

Buyan N, Bilge I, Turkmen MA, Bayrakci U, Emre S, Fidan K, Baskin E, Gok F, Bas F, Bideci A. Post‐transplant glucose status in 61 pediatric renal transplant recipients: Preliminary results of five Turkish pediatric nephrology centers.
Pediatr Transplantation 2010:14:203–211 © 2009 John Wiley & Sons A/S. Abstract: To assess the incidence, risk factors and outcomes of PTDM, a total of 61 non‐diabetic children (24 girls, 37 boys, age: 14.5 ± 2.1 yr) were examined after their first kidney transplantation (37.3 ± 21.6 months) with an OGTT. At baseline, 16 (26.2%) patients had IGT, 45 (73.8%) had NGT, and no patient had PTDM. No significant difference was shown between TAC‐ and CSA‐treated patients in terms of IGT. Higher BMI z‐scores (p = 0.011), LDL‐cholesterol (p < 0.05) and triglyceride levels (p < 0.01), HOMA‐IR (p = 0.013) and lower HOMA‐%β (p = 0.011) were significantly associated with IGT. Fifty‐four patients were re‐evaluated after six months; eight patients with baseline IGT (50%) improved to NGT, three (19%) developed PTDM requiring insulin therapy, five (31%) remained with IGT, and four patients progressed from NGT to either IGT (two) or PTDM (two). These 12 progressive patients had significantly higher total cholesterol (p < 0.05), triglycerides (p < 0.05), HOMA‐IR (p < 0.01) and lower HOMA‐%β (p < 0.0) than non‐progressive patients at baseline. We can conclude that post‐transplantation glucose abnormalities are common in Turkish pediatric kidney recipients, and higher BMI z‐scores and triglyceride concentrations are the main risk factors. Considering that the progressive patients are significantly more insulin resistant at baseline, we suggest that the utility of both HOMA‐IR and HOMA‐%β in predicting future risk of PTDM and/or IGT should be evaluated in children.     

Overweight and obesity in pediatric liver transplant recipients: prevalence and predictors before and after transplant, United Network for Organ Sharing Data, 1987-2010

Perito ER, Glidden D, Roberts JP, Rosenthal P. Overweight and obesity in pediatric liver transplant recipients: Prevalence and predictors before and after transplant, United Network for Organ Sharing Data, 1987–2010.
Pediatr Transplantation 2012: 16: 41–49. © 2011 John Wiley & Sons A/S. Abstract: Obesity is extremely common in adult liver transplant recipients and healthy U.S. children. Little is known about the prevalence or risk factors for post‐transplant obesity in pediatric liver transplant recipients. UNOS data on all U.S. liver transplants 1987–2010 in children 6 months–20 yr at transplant were analyzed. Subjects were categorized as underweight, normal weight, overweight, or obese by CDC guidelines. Predictors of weight status at and after transplant were identified using multivariate logistic regression. Of 3043 children 6–24 months at transplant, 14% were overweight. Of 4658 subjects 2–20 yr at transplant, 16% were overweight and 13% obese. Children overweight/obese at transplant were more likely to be overweight/obese at one, two, and five yr after transplant in all age groups after adjusting for age, ethnicity, primary diagnosis, year of transplant, and transplant type. Weight status at transplant was not associated with overweight/obesity by 10 yr after transplant. The prevalence of post‐transplant obesity remained high in long‐term follow‐up, from 20% to 50% depending on age and weight status at transplant. Weight status at transplant is the strongest predictor of post‐transplant overweight/obesity. To optimize long‐term outcomes in pediatric liver transplant recipients, monitoring for obesity and its comorbidities is important.     

Living donor liver transplantation in Alagille syndrome—Single center experience from south Asia

To analyze the clinical characteristics and the outcomes of living donor liver transplantation in children with Alagille syndrome (AGS). Clinical data of children with AGS who underwent liver transplantation between July 2009 and May 2019 in our unit were retrospectively analyzed. Primary end‐points were patient and graft survival. Ten children with AGS underwent living donor liver transplantation at a median age of 28 months (range, 12‐84 months). Jaundice was the most common initial symptom and was noted after a median duration of 20 days after birth (range, 7‐60 days). Two patients had undergone Kasai porto‐enterostomy for misdiagnosis of biliary atresia. The most common indication for transplantation was severe pruritus with poor quality of life. Explant livers in three children showed cirrhosis with early well‐differentiated hepatocellular carcinoma. We have 100% patient and graft survival at a mean follow‐up of 32 months (range 3‐72 months). The median z‐score for weight and height at liver transplantation was ?2.66 (range: ?6.44 to ?0.9) and ?3.6 (range: ?7.96 to ?0.93) while at follow‐up was ?1.7 (range: ?3.4 to ?0.35) and ?2.1 (range: ?3.9 to ?1.4), respectively. The estimated glomerular filtration rate was normal pretransplant and follow‐up. This is the first series of LDLT for Alagille syndrome in the Indian sub‐continent. We report excellent post‐transplant outcomes in contrast to outcomes reported from Western literature.