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.     

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.     

Evaluating non-adherence to immunosuppressant medications in pediatric liver transplant recipients

Abstract:  Non-adherence with recommended immunosuppressant medications is common post-pediatric liver transplant and is the most important reason for organ rejection in long-term survivors. However, there is currently no validated, standard method to measure adherence, with a well-defined threshold, making it extremely difficult to evaluate interventions to improve adherence. Previous studies have suggested that the degree of fluctuation of medication blood levels over time can provide an idea about how regularly the medication is being taken. The present study, conducted at UCLA medical center, sought to identify a specific threshold value of the s.d. of individual tacrolimus blood levels in pediatric liver transplant recipients which would be associated with rejection episodes in these patients. A threshold of 3.0 has been identified in other studies, and was supported by the analysis of retrospective data from 96 subjects. However, further analysis found that a s.d. of 2.5 appeared to have a better fit with the data. These findings suggest the utility of monitoring the s.d. of routine tacrolimus blood levels in pediatric liver transplant recipients for detecting non-adherence to immunosuppressant medication prior to clinical rejection, allowing earlier interventions.     

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.     

Assessing allocation of responsibility for health management in pediatric liver transplant recipients

Given the increased risk for non‐adherence and poor health outcomes in late adolescence, there is a need for better methods to evaluate and improve the transition process as adolescent patients are prepared to be independent adults. This study assessed the psychometrics and concurrent validity of a newly developed measure of AoR for health management in pediatric liver transplant patients. A total of 48 patients and 37 parents completed a 13‐item measure of AoR. We performed an exploratory PCA on survey results and used component scores to assess the relationship between AoR and age, age at transplant, adherence, and health outcomes. Two primary components were identified: communication with the healthcare system and self‐management tasks. Parent perception of adolescent responsibility for tasks related to communicating with the healthcare system was correlated, in younger patients, with increased non‐adherence while responsibility for tasks related to self‐management was correlated, in older patients, with decreased non‐adherence. These results support AoR as a two‐domain construct, and they provide targets for monitoring and intervention as adolescent patients advance toward transfer.     

Lipid profile and cardiovascular risk factors in pediatric liver transplant recipients

Cardiovascular diseases induce long‐term morbidity and mortality of adult LT recipients. The aim of this retrospective study was to assess CVRF, lipid abnormalities, and atherosclerosis (appraised by c‐IMT), more than 10 yr after pediatric LT. Thirty‐one children who underwent LT between December 1990 and December 2000 were included. Median age at LT was 14 months (range 4–64), and median follow‐up after LT was 11.9 yr (range 9.0–17.3). In our cohort, obesity (9.7%) and treated hypertension (9.7%) were rare. None of the patients was smoker or diabetic. High TC and TG were both observed in 6.5% of the patients. The mean c‐IMT for male patients was 1.22 ± 1.55 and 1.58 ± 1.23 mm in female patients. Seven patients (22%) had a mean c‐IMT above +2 s.d. Values below the 5th percentile were noted for LDL‐cholesterol (58.1%), HDL‐cholesterol (25.8%), apolipoprotein B (40%), and apolipoprotein A1 (20%). LDL‐cholesterol and apolipoprotein B levels were significantly lower in patients treated by tacrolimus in comparison with CsA (p < 0.05). In conclusion, our results suggest that pediatric LT patients do not present significant CVRF; moreover, instead of hyperlipidemia, hypocholesterolemia (LDL‐C) is frequent and immunosuppressive therapy is probably the cause.     

Medication adherence in the transition of adolescent kidney transplant recipients to the adult care

Non‐adherence is common in adolescent and young adult kidney transplant recipients, leading to adverse graft outcomes. The aim of this study was to determine whether adherence to immunosuppressant medications changes during transition from a pediatric to an adult program within the same transplant center. Adherence was assessed for a period of two yr before and two yr after the transfer. Subtherapeutic trough levels of serum tacrolimus and level variability were used as measures of adherence. Twenty‐five patients were transitioned between 1996 and 2011 at the median age of 22.3 [IQR 21.6–23.0] yr. Young adults 21–25 yr of age (n = 26) and non‐transitioned adolescents 17–21 yr of age (currently followed in the program, n = 24 and those that lost their grafts prior to the transfer, 22) formed the comparison groups. In the transitioned group, adherence prior to the transfer was not significantly different from the adherence after the transfer (p = 0.53). The rate of non‐adherence in the group of non‐transitioned adolescents who lost their grafts (68%) was significantly higher than in the transitioned group (32%, p = 0.01). In the group of young adults, adherence was not significantly different from the transitioned group (p = 0.27). Thus, transition was not associated with differences in medication adherence in this single‐center study. Large‐scale studies are needed to evaluate the national data on medication adherence after transfer.     

Growth of liver allografts over time in pediatric transplant recipients

The liver's capacity to grow in response to metabolic need is well known. However, long‐term growth of liver allografts in pediatric recipients has not been characterized. A retrospective review of pediatric recipients at a single institution identified patients who had cross‐sectional imaging at 1, 5, and 10 years post‐transplant. Using volumetric calculations, liver allograft size was calculated and percent SLV were compared across the different time points; 18 patients ranging from 0.3 to 17.7 years old were identified that had imaging at 2 or more time points. Measured liver volumes increased by 59% after 5 years and 170% after 10 years. The measured liver volumes compared to calculated %SLV for these patients were 123 ± 37%, 97 ± 19%, and 118 ± 27% at 1, 5, and 10 years after transplant, respectively. Our data suggest that liver allografts in pediatric recipients increase along with overall growth, and reach SLVs for height and weight by 5 years post‐transplantation. Additionally, as pediatric recipients grow, the livers appear to maintain appropriate SLV.     

A typology of non-adherence in pediatric renal transplant recipients

We reviewed 112 pediatric renal transplant recipients to document the rate of medication non-adherence (NA) and to examine the relationships between NA, comorbid psychiatric illness, and the outcome variables of acute and chronic rejection and graft loss. A total of 32.5% of subjects had clinically significant NA with treatment based on review of serum immunosuppressant levels. NA was found to be significantly related to acute and chronic rejection, and graft loss (p < 0.001). NA was also related to the presence of comorbid psychiatric illness (p < 0.001). Logistic regression indicated that NA was a significant predictor for acute and chronic rejection, while psychiatric illness predicted graft loss. Adolescents had significantly higher rates of NA as well as shorter intervals between transplant date and onset of NA when compared with child patients (p < 0.001). Physician ratings of the primary reasons for NA suggested that lack of parental supervision and parent-child conflict were the major factors related to NA.     

Fatigue in pediatric liver transplant recipients and its impact on their quality of life

The aim of the study was to investigate the occurrence of fatigue in 100 pediatric liver transplant recipients aged 2‐18 years and its impact on their health‐related quality of life (HRQL). HRQL and fatigue were measured using the PedsQL 4.0 Inventory and the PedsQL Multidimensional Fatigue Scale, which encompasses three subscales: general fatigue, sleep/rest fatigue, and cognitive fatigue. The impact of the different domains of fatigue and of clinical and sociodemographic factors on the HRQL was identified with stepwise multiple regression analyses. Parent proxy‐reports were available for all 100 participants (2‐18 years), and child self‐reports were available for 71 patients (8‐18 years). Across all domains, participants and their parents reported significantly more fatigue than healthy peers in a large PedsQL validation study. Thirty‐seven percent of patients and 57% of parents scored clinically relevant levels of fatigue. In the multiple regression analyses, none of the clinical and sociodemographic factors contributed to the HRQL for child self‐report. Only general and cognitive fatigue were significant predictors of patients' HRQL, explaining 66% of the variance in the PedsQL total score. For parent proxy‐report, general and cognitive fatigue also significantly predicted child's HRQL. Further predictors were child's age and family income. The regression model explained 65% of the variance. These findings demonstrate the importance of assessing fatigue during regular follow‐up examinations. Further research is urgently needed to better understand the underlying mechanisms of fatigue. Improvement of fatigue symptoms is essential for better HRQL, for cognitive functioning, and for school achievement.     

Outcome of pediatric liver transplant recipients in Turkey: single center experience

To summarize the evolution of the pediatric liver transplant program in a developing country. Between April 1997, and September 2003, 32 cadaveric (CD) and 35 living donor (LD) liver transplantations were performed on 61 children (median age 3.8 yr, range 0.5-16) at Ege University Organ Transplantation and Research Center. The patient's charts were reviewed retrospectively. The outcome of patient and graft survival was analyzed and the incidence of graft loss, complications and rejections was calculated. Indications for liver transplantation were metabolic liver disease (n = 17), biliary atresia (n = 14), viral hepatitis (n = 4), autoimmune hepatitis (n = 6), cryptogenic cirrhosis (n = 11), fulminant liver failure (n = 5) and others (n = 5). Seven of 61 children with chronic liver disease had hepatocellular carcinoma concomitantly. Median pediatric end-stage liver disease score was 23 (range 1-54). Seven children (11.4%) were UNOS status I, 44 (72%) were UNOS status II and 10 (16.6%) were UNOS status III. The median follow-up of the study population was 3.6 yr (range 0.5-6). Actuarial patient survival rates at 1, 2, 3 and 4 yr were 86, 86, 71.3 and 65% in the CD group vs. 80, 76, 67 and 67% in the LR group, respectively (p = NS). Patients listed as UNOS status 1 had lower survival rates than patients listed as UNOS status 2 and 3 (p < 0.05). The mortality rate was 26.2%. Graft survival rates were 81, 81, 75 and 64% at 1, 2, 3 and 4-yr respectively. Six patients (9%) underwent retransplantation. The main complications were infections (64.7%) and surgical complications (43.2%) (including biliary complication, vascular problems, postoperative bleeding, small for size and large for size). The incidence of acute cellular rejection was 39.3%, whereas chronic rejection was 7.4%. The result of liver transplantation in Turkish children was slightly inferior to those reported for North American and European children. However, an important characteristic of these patients that distinguishes them from Europe and North America is that most were UNOS status IIa and UNOS status I (44%). Despite technical and medical progress, infectious and biliary problems have continued to be an important cause of mortality in these patients.     

Presentation of atopic disease in a large cohort of pediatric liver transplant recipients

Atopic disease occurs in solid organ transplant recipients with an increasingly recognized frequency. The time course for the development of these atopic diseases in liver transplantation has not been described. The objective was to characterize the atopic manifestations of children receiving chronic immunosuppression after orthotopic liver transplantation (OLT). Chart review and follow-up questionnaire were utilized for 176 OLT pediatric recipients at a single institution for manifestations of allergic disease. Atopic disease was present in 25 (14.2%) patients. Median age at transplant was 16 months with a median follow-up of 63 months. Food allergy and non-food related atopic symptoms presented at a median of 11.5 (IQR, 6-28) and 19 (IQR, 5-41) months post-transplantation, respectively. The median age at transplant of the non-atopic children was 72 months, higher than patients with atopy (p < 0.001). Food allergy and atopic skin disease symptoms were present in 40% and 56% of cases, respectively. Asthma, allergic rhinitis, or both were found in 66% of cases. The onset of symptoms of food allergy and eczema (median, 12 months post-transplantation) preceded symptoms of allergic rhinitis and asthma. (median of 27 and 30 months post-transplantation, respectively). Atopy occurs in ～14% of pediatric liver transplant recipients, with manifestations including food allergy, eczema, allergic rhinitis, and asthma.     

Utility of liver biopsy culture in pediatric liver transplant recipients

Abstract: The purpose of our study was to determine the utility of the practice of culturing percutaneous liver biopsy specimens obtained from pediatric LT recipients for evaluation of fever and/or elevated serum aminotransferases. Accordingly, a retrospective analysis was done of the 101 liver biopsies obtained during an eight-year period which had been submitted for bacterial, fungal and/or viral culture (out of a total of 174 biopsies in 38 patients). The purpose of the analysis was to ask three questions. (1) What organisms were cultured? (2) Were there clinical profiles that were characteristic of the type of organism? (3) Was the practice cost-effective? The analysis indicated that 34/86 biopsy cultures were positive for bacteria, 4/75 for fungus and 2/81 for virus. Clinical and laboratory data for children with cultures positive for enteric flora (n = 9) were compared to those with cultures positive for Gram-positive organisms (n = 17), laboratory contaminants (n = 8), and those with negative cultures (n = 52). Children with biopsies positive for enteric flora had a ‘cholestatic profile’: mean direct bilirubin 7 mg/dl, ALT 78 IU/l, direct bilirubin/ALT 0.09, in comparison to children with biopsies positive for Gram-positive flora. These children had a ‘hepatocellular profile’: mean direct bilirubin 4 mg/dl, ALT 332 IU/l, direct bilirubin/ALT 0.01 (p = 0.04 versus the enteric flora values) and a high percentage of polymorphonuclear leukocytes (mean 69% versus 38% for those with negative cultures, p = 0.001.) The charge for performing each bacterial culture was $28 (total $28 × 86 = $2408: $268 per enteric flora-positive biopsy; $93 per biopsy positive for either enteric flora or Gram-positive flora). The charge for each fungal culture was also $28 (total $28 × 75 = $2100: $525 per positive culture), while the cost for each viral culture was $140 (total $140 × 81 = $11 340: $5670 per positive culture). Thus, discounting the eight cultures positive for laboratory contaminants, a total of $15 848 was spent for 32 positive cultures. Given the high cost of liver transplantation, this information suggests that discretion should be used in submission of liver biopsy samples for culture in pediatric transplant patients. We recommend that when liver biopsies are performed for evaluation of elevated serum aminotransferases and/or fever, culture of biopsy specimens for bacteria should be considered in children with a ‘cholestatic profile’: direct bilirubin ≥ 7 mg/dl and direct bilirubin/ALT > 0.08, or a ‘hepatocellular profile’: direct bilirubin ≤ 4 mg/dl and direct bilirubin/ALT < 0.05, together with polymorphonuclear leukocytes > 70%. Following these guidelines might provide valuable information pertinent to patient management (especially since Gram-negative organisms can sometimes be cultured from the liver and not from blood) while reducing costs. Fungal cultures should be restricted to critically ill children. However, our data suggest that the practice of obtaining fungal and viral cultures of the liver in most pediatric transplant patients has an unacceptably high cost/benefit ratio, particularly since recovery of the organism from the peripheral blood is likely.     

Immediate tracheal extubation of pediatric liver transplant recipients in the operating room

Keeping patients on mechanical ventilation after orthotopic liver transplantation (OLT) has been a standard anesthetic approach since the first utilization of liver transplantation. Advances in anesthetic management, surgical techniques and patient preparation, in addition to improved postoperative care and the reported advantages of early postoperative tracheal extubation of liver recipients. encouraged us to extubate most recipients at the end of the operation. The aim of the present study is to evaluate the pediatric liver recipients who were extubated immediately at the end of transplantation, in terms of respiratory complications and allograft function during their stay in the ICU. We retrospectively reviewed the records of 40 pediatric recipients who had undergone OLT at the Ege University Organ Transplantation Center between December 1997 and July 2002. Twelve out of 40 patients who had consecutively undergone OLT were extubated immediately at the end of the operation and were included this study. Mean Child Pugh scores of the patients were 9 +/- 2.3 (range 6-12) and the mean PELD score was 23.1 +/- 12.3 (range 7-41). The mean age of the patients was 8.4 +/- 5.2 (range 0.8-16.8 yr). Five of the 12 extubated patients received a cadaveric and seven a living donor liver graft. The mean ICU stay of the patients was 49.1 +/- 24.2 h (6-120 h). No patients required reintubation or mechanical ventilation in the ICU. Respiratory complications diagnosed in the 12 extubated patients were hypercapnia without hypoxemia in three, atelectasis in one and pleural effusion in two. No primary non-function or delayed graft function was detected. The aspartate transaminase (AST), alanine transaminase (ALT) and protrombin time (PT) were normalized within a week. We believe that immediate tracheal extubation in the operating room is a safe procedure for selected cadaveric and living-related liver transplant recipients and will facilitate the patients' recovery and mobilization leading to reduction in complications and a reduced ICU stay.     

Hypogammaglobulinemia in pediatric liver transplant recipients

Hypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post-transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine-based standard immunosuppression. Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post-Ltx the serum IgG was 1.7 g/L. Patient 2 was transplanted at the age of 12 yr for acute liver failure. Four weeks post-Ltx the IgG dropped to 2.6 g/L. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post-Ltx severe hypogammaglobulinemia (IgG < 1.48 g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post-operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10 months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary.     

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.     

Epstein‐Barr viral load monitoring for diagnosing post‐transplant lymphoproliferative disorder in pediatric liver transplant recipients

This study aimed to investigate the incidence of PTLD in pediatric liver transplant recipients and the risk factors for the development of PTLD. We also determined clinically useful quantitative EBV PCR parameters for aiding in the diagnosis of EBV‐associated PTLD in the pediatric liver transplant recipients at our institute. We reviewed children < 18 years old who had undergone liver transplantations and quantitative analysis of whole blood EBV load at our institute from January 2006 to March 2015. A total of 142 liver transplant recipients were included, and their median age was 1.5 years. Clinically significant high‐level EBV DNAemia ≥ 10 000 copies/mL at least twice was observed in 53.5% and PTLD occurred in 9.9%. Among PTLD group, graft failure and mortality rate were as high as 21.4% and 14.3%, respectively. Deceased donor, presence of high‐level EBV DNAemia, and primary CMV infection following transplant were associated with an increased risk for PTLD in the multivariate analysis. The peak titer at 10 875 copies/mL could be used as a cutoff value with a sensitivity of 92.9% and a specificity of 37.9%; the rate of increase in EBV load suggested a sensitivity of 64.3% and a specificity of 70.9% at the cutoff value of 44 000 copies/mL/week. In conclusion, the incidence of PTLD following liver transplant in children was as high as 10%. PTLD is associated with significant morbidity and mortality. Close monitoring of EBV DNAemia is crucial for the early diagnosis and proper treatment of PTLD in pediatric liver transplant recipients.     

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.     

Longitudinal stability of medication adherence among adolescent solid organ transplant recipients

Solid organ transplantation requires ongoing adherence to immunosuppressants and other medications. Although adolescence is a risk factor for poor medication‐taking, little is known about the patterns of adherence within individuals over time. This study aimed to examine the stability of adherence over time using three different assessment techniques. Sixty‐six AYA transplant recipients and/or their caregiver completed interviews of adherence at baseline and at least one yr later. Serum immunosuppressant assay levels were collected via medical chart review. Non‐adherence percentages based on AYA report, caregiver report, and bioassay did not differ from Time 1 to Time 2. However, correlations for these measures across time were non‐significant. Further, the majority of AYAs shifted to a different adherence category from Time 1 to Time 2. Overall, these results demonstrate individual variability in non‐adherence over the course of adolescence and young adulthood and highlight the importance of frequent assessment across time for solid organ transplant recipients.     

An objective measure to identify pediatric liver transplant recipients at risk for late allograft rejection related to non-adherence

Non-adherence to a prescribed immunosuppressive regimen increases risk for late allograft rejection (LAR). We implemented a protocol for immunosuppression management which decreased variation in calcineurin inhibitor blood levels in pediatric liver transplant recipients by controlling for confounders such as physician practice variability. We hypothesized that patients with increased variation in tacrolimus blood levels despite implementation of the immunosuppression management protocol were at increased risk for LAR. We conducted a single center retrospective cohort study of 101 pediatric liver transplant recipients who were at least one year post liver transplantation and receiving tacrolimus for immunosuppression. The primary outcome variable was biopsy proven allograft rejection. Primary candidate predictor variables were the standard deviation (SD) of tacrolimus blood levels (a marker of drug level variability), mean tacrolimus blood level, age, and insurance type. SD of tacrolimus blood levels was determined for each patient from a minimum of four outpatient levels during the study period. Unadjusted and adjusted logistic regression models were used to determine the prognostic value of candidate predictors. The median and interquartile range of the SD of tacrolimus blood levels was 1.6 (1.1, 2.1). Eleven episodes of LAR occurred during the study period. Ten of the 11 episodes occurred in patients with tacrolimus blood level SD > 2. Insurance type, mean tacrolimus blood level and SD of tacrolimus blood levels were significantly related to LAR in the unadjusted analyses (p<0.05). A multivariable model including age, insurance type, mean and SD of tacrolimus blood levels was significantly associated with LAR (validated C-statistic = 0.88, p = 0.012). The adjusted odds of rejection for a one unit increase in the SD of tacrolimus blood level was 3.49 (95% CI 1.31 to 9.29). Effects of age and insurance status on LAR did not provide independent prognostic value after controlling for SD. Variation in tacrolimus blood levels is associated with an increased risk of LAR in pediatric liver transplant recipients. Despite standardized management of tacrolimus levels to control for confounders, some patients were found to have significant variability of tacrolimus blood levels. This may be due to non-adherence and amenable to targeted psychosocial and behavioral interventions to prevent LAR.