Adherence and medical outcomes in pediatric liver transplant recipients who transition to adult services

Non-adherence to medications is associated with poor medical outcomes in adolescent transplant recipients. It is unclear whether non-adherence is further compromised when transplant recipients transition to the adult health care system. The purpose of the present study was to examine whether adherence changes during transition. We reviewed the medical records of 14 recently transitioned patients and compared their adherence and corresponding medical outcomes before and after transition. These outcomes were also compared with two cohorts of patients receiving care solely in pediatric or adult services. Medication adherence, measured through the use of standard deviations of tacrolimus blood levels, was examined for all patients. We found that adherence to tacrolimus significantly decreased after transition. After transitioning, patients furthermore exhibited poorer adherence than patients in the other two cohorts did over time. This small retrospective study suggests that the period of transition from pediatric to adult transplant clinics is a vulnerable one. Larger, prospective investigations of the transition process are necessary before recommendations are made regarding interventions.     

A translational and systemic approach to transferring liver transplant recipients from pediatric to adult‐oriented care settings

Annunziato RA, Hogan B, Barton C, Miloh T, Arnon R, Iyer K, Kerkar N. A translational and systemic approach to transferring liver transplant recipients from pediatric to adult‐oriented care settings.
Pediatr Transplantation 2010: 14:823–829. © 2010 John Wiley & Sons A/S. Abstract: The purpose of this review is to (i) describe systemic changes made in our clinical practice to facilitate transfer of transplant recipients from the pediatric to the adult service and (ii) provide the rationale for instituting these organizational changes. To determine specific areas patients struggle to master, a survey assessing behaviors indicative of health care management was administered in pediatrics. Based on the results of the survey, all liver transplant recipients who transfer out of pediatrics are given a comprehensive clinical protocol, which includes a transfer checklist containing prerequisite items derived from our prior work. Patients are furthermore invited to enroll in a research study prospectively tracking both medical and psychosocial outcomes at six‐month intervals. Data are discussed by the pediatric and adult teams, and additional adjustments to the transfer process are implemented in response. A summary of our clinical interventions and the resources required for implementation are presented. In conclusion, preliminary studies have demonstrated that transplant recipients are vulnerable to disruptions in health care management when they transfer out of pediatrics. This study describes one site’s translational efforts to improve the transfer process for both the recipients and the clinicians, thus improving outcomes.     

Fatal hyperammonemia associated with disseminated Serratia marcescens infection in a pediatric liver transplant recipient

Hyperammonemia is a rare and important complication post‐liver transplantation. We review a case of a 5‐month‐old boy with biliary atresia who received a split liver transplant following a variceal bleed. The transplant was complicated by recurrent portal vein thrombosis. Colonized with Serratia marcescens pretransplant, he developed disseminated infection associated with very high levels of ammonia that led to his death. It is important to be aware of serum ammonia levels in patients with portal vein thrombosis, particularly in the setting of gastrointestinal bleeding and sepsis.     

Transition to adult care for pediatric liver transplant recipients: the Western Australian experience

Transition to adult care is a vulnerable period for pediatric transplant recipients and is associated with reduced medication compliance, graft loss, and increased mortality. Psychosocial outcomes in young adults differ between pediatric transplant recipients and their healthy peers. We conducted a single‐center, retrospective cohort study of all pediatric liver transplant recipients who were transitioned through our center. This study aimed to assess the outcomes of transitioned pediatric liver transplant recipients at an Australian center, including mortality, adherence, and psychosocial morbidity. The 1‐ and 5‐year survival rates following transition were 100% and 92%, respectively. There were no episodes of late rejection. In total, 66.7% of patients were compliant with immunosuppression and 61.1% of patients were compliant with clinic attendance. There was a significant relationship between medication compliance and clinic attendance, as well as presence of psychological issues with clinic non‐attendance. Psychosocial outcomes were in keeping with age‐matched data from the general population. All patients were employed or studying following transition. This is the first study of its kind in the Australian population, and outcomes were superior to published international data. Despite the demonstrated good outcomes, transition programs may improve healthcare engagement in this cohort.     

Use of tissue expansion to facilitate liver and small bowel transplant in young children with contracted abdominal cavities

Liver and small bowel transplant is an established treatment for infants with IFALD. Despite organ reduction techniques, mortality on the waiting list remains high due to shortage of size‐matched pediatric donors. Small abdominal cavity volume due to previous intestinal resection poses a significant challenge to achieve abdominal closure post‐transplant. Seven children underwent tissue expansion of abdominal skin prior to multiorgan transplant. In total, 17 tissue expanders were placed subcutaneously in seven children. All seven subjects underwent re‐exploration to deal with complications: hematoma, extrusion, infection, or port related. Three expanders had to be removed. Four children went on to have successful combined liver and small bowel transplant. Two children died on the waiting list of causes not related to the expander and one child died from sepsis attributed to an infected expander. Tissue expansion can generate skin to facilitate closure of abdomen post‐transplant, thus allowing infants with small abdominal volumes to be considered for transplant surgery. Tissue expansion in children with end‐stage liver disease and portal hypertension is associated with a very high complication rate and needs to be closely monitored during the expansion process.     

Transition of pediatric liver transplant recipients to adult care: patient and parent perspectives

The need to prepare pediatric transplant recipients for the transfer to adult-centered transplant care has received increased attention. This study aimed to determine adolescent and young adult LTR and parent perceptions and attitudes about the transition process. LTR and their parents completed a survey assessing level of prior thought and interest in learning about transferring care, knowledge of the transition process, perceived importance of self-management skills, concerns about moving to the adult clinic, and responsibility for health management tasks. Responses were analyzed by age, gender, and time since transplantation. Participants included 46 LTR (mean age = 16.6 yr; range 12-21), and 31 parents. Recipients and parents reported moderate concern about transition, with leaving pediatric providers being a primary worry. LTR ≥16 yr reported greater health care responsibility and increased thought, interest, and knowledge about transition. There were significant differences between parent and LTR perceptions of health care responsibility, indicating that LTR perceive having more independence than what their parents report. Overall, results suggest that adolescent and young adult LTR and their parents perceive the importance of transitional care, but demonstrate poor knowledge of the process. There remains a need for improved transition planning for both adolescents and parents.     

Parents and clinicians underestimate distress and depression in children who had a transplant

The present study examined whether there are differences in reporting of depressive and post-traumatic stress symptoms between children who had a transplant and children who had other medical illnesses. We evaluated both the child's report about her/his symptoms and the parent or the clinician's report about these symptoms in the child. Scores on measures of depression (clinician rated vs. child rated) and post-traumatic stress (parent rated vs. child rated) were compared between medically ill children who have vs. have not had a solid organ transplant. The findings of a psychiatric evaluation are also reported. Children who have vs. have not received a solid organ transplant reported the same levels of depression and post-traumatic stress, while adults (their parents or clinicians who evaluated them) reported lower levels of depression and post-traumatic stress in the transplant group. The psychiatric evaluation revealed no differences between the groups. Children view their post-transplant course differently from adults caring for these children. Adults tend to underestimate the child's post-transplant emotional symptoms, possibly because they focus on the improved prognosis (whereas the children focus on the concrete experience of illness). The child's report of his or her emotional symptoms should be directly sought post-transplant.     

Treatment of adenovirus hepatitis with cidofovir in a pediatric liver transplant recipient

AdV hepatitis is a rarely reported complication after pediatric liver transplantation that is associated with high rates of morbidity, mortality and graft failure. Successful treatment of AdV relies on early diagnosis of disease by quantitative PCR measurement of adenoviral DNA in blood and histological evidence in tissue biopsy. Pharmacologic treatment largely consists of antiviral therapy with CDV, an acyclic nucleoside phosphonate analog and reduction in immunosuppression. This report describes a case of AdV hepatitis in a pediatric liver transplant recipient successfully treated with a modified, renal sparing dosing of CDV.     

Preparing for transition: The effects of a structured transition program on adolescent heart transplant patients’ adherence and transplant knowledge

Transition to adult health care has become a mainstream focus in pediatric health care as a higher percentage of patients are surviving into adulthood. This study investigated the success of a structured educational transition program in improving pediatric heart transplant patients’ overall medical knowledge, medication adherence, readiness to transition, as well as parental perceptions of their child's readiness to transition to aid in the successful transition to an adult heart transplant program. Patients underwent a structured transition program over 2 years that included a total of seven 2‐hour educational sessions hosted quarterly. This study comprised of a retrospective review of 12 heart transplant patients between the ages of 16‐22 years . Test results indicated a statistically significant increase in overall medical knowledge scores from presession assessment compared to post‐session assessment. Participants remained confident in their ability to transition throughout the program. Further, a statistically significant decrease in participant non‐adherence was observed, as percentage of calcineurin inhibitor levels determined to be out of range decreased over the course of the program. Results suggest that a structured transition program is effective in improving overall patient medical knowledge in relation to their heart transplant and enhancing patient medication adherence. To effectively facilitate transition, pediatric providers, caregivers, and patients must communicate to provide a purposeful planned transition experience from pediatric to adult health care.     

Analysis of clinical variables associated with tolerance in pediatric liver transplant recipients

Tolerance has been defined as stable graft function off IMS. We reviewed the data of 369 pediatric liver transplant patients to examine demographic differences that may have a PV of pediatric LT tolerance. Of the 369 patients, 280 patients were stable with detectable blood levels of IMS agents and with good graft function without biopsy proven REJ > 1 yr posttransplantation, 18 patients were noted to be TOL off IMS, 27 patients were taking MIS with drug levels below detectable range by standard laboratory parameters, and 44 patients developed one or more episodes of biopsy proven acute or chronic REJ > 1 yr post-transplantation. Variables, including percentage of biliary atresia, type of transplanted organ, history of EBV infection, patient and donor gender, and ABO blood type mismatch between recipient and donor did not have PV of tolerance. Average age in years was 1.37 ± 1.53 (0.3-4.9) for TOL, 1.14 ± 0.89 (0.4-3.1) for MIS and 3.35 ± 4.45 (0.3-16) for REJ. Age difference of TOL/MIS vs. REJ was significant (p =0.002) and TOL vs. REJ was significant (0.01). Age at the time of transplantation is an important predictor in the development of pediatric LT tolerance.     

Long-term follow-up in adult living donors for combined liver/bowel transplant in pediatric recipients: a single center experience

Pediatric candidates for combined liver/bowel transplant (LBTx) experience a very high mortality on the cadaver waiting list. Our transplant center has successfully used adult living donors to treat pediatric candidates for LBTx. We report the long-term follow-up of this unique cohort of organ donors. The charts of six adult donors for LBTx performed between 2004 and 2007 were reviewed. All the pertinent clinical data were carefully reviewed and integrated with phone interviews of all donors. A total of six children (average age 13.5 months) received living donor LBTx. Average follow-up for the donors was 42 months (range 29-51). The donors' median age was 25 yr (19-32); five women and one man. The average median hospital stay was nine days. There were no peri-operative complications. At present all donors remain in good health. Three of the five mothers became pregnant after donation. Five of the six children are currently alive and well whereas one died with functioning grafts six months post-transplant due to plasmoblastic lymphoma. Living donor LBTx is an effective therapy for combined hepatic and intestinal failure in children less than five yr. The donor operation can be performed with minimal morbidity.     

Neurological toxicity of acyclovir: report of a case in a six-month-old liver transplant recipient

Abstract:  Acyclovir-induced neurotoxicity is a rare adverse effect, found especially in adults with pre-existing renal failure. We report a case of neurotoxicity of acyclovir in a six-month-old liver transplant recipient. Case report and review of literature are discussed.     

Evaluation of cardiac manifestations in pediatric liver transplant candidates

Knowledge concerning the involvement of the cardiovascular system in children awaiting liver transplant is limited. Therefore, no guidelines have been established on evaluating this group of patients for cardiac disease. This review examines the diverse cardiovascular manifestations of liver disease in children. We also discuss the available testing and its applicability in screening for cardiac disease in this vulnerable population.     

Assessment of transition readiness skills and adherence in pediatric liver transplant recipients

Fredericks EM, Dore‐Stites D, Well A, Magee JC, Freed GL, Shieck V, Lopez MJ. Assessment of transition readiness skills and adherence in pediatric liver transplant recipients.
Pediatr Transplantation 2010: 14:944–953. © 2010 John Wiley & Sons A/S. Abstract: To examine transition readiness, adherence, and health outcomes in pediatric liver transplant recipients using a clinically administered screening measure. Seventy‐one pediatric liver transplant recipients (11–20 yr) and 58 parents completed a clinic‐based TRS measuring perceived and demonstrated self‐management skills, AoR for health‐related tasks, regimen knowledge, and psychosocial adjustment. Adherence was measured using s.d. of immunosuppressants, proportion of immunosuppressant blood levels out of target range, and clinic attendance. Health outcomes included liver test panels, biopsies, rejection episodes, and hospitalizations. Results indicate that all domains of transition readiness, with the exception of demonstrated skills, and non‐adherence were positively correlated with age. Proportion of immunosuppressant blood levels below target range was positively correlated with self‐management skills and increased responsibility for medication tasks. Parent regimen knowledge was associated with clinic attendance. Health outcomes were significantly related to medication non‐adherence, but not to transition readiness domains. Medication adherence is considered to be a key factor in the transition from pediatric to adult‐centered transplant care. Non‐adherence is associated with an increased risk for medical complications and is potentially modifiable. Interventions to promote self‐management skills and adherence should be an essential component of transition planning.     

Successful outcome after early combined liver and en bloc-kidney transplant in an infant with primary hyperoxaluria type 1: A case report

Abstract:  PH1 is a metabolic disorder characterized by urolithiasis and the accumulation of oxalate crystals in the kidneys and other organs. Although patients often first present with renal failure, PH1 results from a deficiency of the hepatic peroxisomal enzyme AGT. Ultimately only liver transplantation will cure the underlying metabolic defect. Herein, we report the case of a three-month-old male infant diagnosed with PH and treated using a combined liver and en bloc- kidney transplant from a single donor. At the time of transplant, the patient was 11 months old and weighed 7.9 kg. He received a full size liver graft and en bloc kidneys from a two-yr-old donor. At 36 months post-transplant, the patient is steadily growing with normal renal and hepatic function. This is one of the first reports of successful liver and en bloc -kidney transplantation with abdominal compartment expansion by PTFE for the infantile form of PH1 in a high risk child before one yr of age. Prompt diagnosis and early referral to a specialized center for liver and kidney replacement offer the best chance for survival for infants with this otherwise fatal disease.