Ronen Arnon

Improved Adherence and Outcomes for Pediatric Liver Transplant Recipients by Using Text Messaging

OBJECTIVE: The goal was to improve immunosuppressant adherence for pediatric patients with orthotopic liver transplants by using text messaging (TM). METHODS: A prospective study of sending TM reminders to the primary medication administrator (patient or caregiver) for pediatric transplant recipients was performed. Patient records were reviewed, comparing the year before and the year of the study. The SD of serum tacrolimus levels was used as an indicator of adherence. RESULTS: Forty-one patients provided consent. The median age was 15 years (range: 1–27 years), and the median age at the time of transplantation was 2 years (range: 4 months to 23 years). Fourteen patients (34%) were male. In 29 of 41 cases, the medications were self-administered by the patient. The mean duration of study was 13 ± 1.5 months. Twenty-two patients were receiving 1 immunosuppressant, 14 were receiving 2, and 5 were receiving 3. Thirteen patients (37%) stopped the study after 4 months. The mean tacrolimus level SD decreased from 3.46 μg/L before the study to 1.37 μg/L (P < .005). The number of immunosuppressants taken and patient self/caregiver medication administration did not significantly affect the results. The number of acute cellular rejection episodes decreased from 12 to 2 during the study. Risk factors for rejection were older age (17.67 vs 13.28 years) and administration of >1 immunosuppressant. CONCLUSION: We observed significant improvement in medication adherence and a reduction in rejection episodes with TM reminders for pediatric recipients of liver transplants.

A Retrospective Single-Center Review of Primary Sclerosing Cholangitis in Children

BACKGROUND & AIMS Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and progressive bile duct fibrosis. There are limited data on pediatric PSC. METHODS We performed a retrospective chart review of 47 pediatric patients with PSC. RESULTS The mean age at diagnosis was 11 +/- 4.9 years. Symptoms occurred before presentation in 81% of patients; inflammatory bowel disease was found in 59% and autoimmune hepatitis (overlap syndrome) in 25% of patients. Magnetic resonance cholangiography revealed both extrahepatic and intrahepatic, isolated intrahepatic, isolated extrahepatic, and no biliary involvement (small-duct PSC) in 40%, 14%, 10%, and 36%, respectively. Advanced fibrosis (stage >II) was present in 65%. Colonoscopy revealed pancolitis, rectal sparing, and normal findings in 24%, 24%, and 18%, respectively. All patients were treated with ursodeoxycholic acid (UDCA); 9 with overlap syndrome also received immunosuppressants. Fifteen patients without overlap syndrome had positive autoimmune markers and responded to UDCA monotherapy. Liver transplantation was performed in 9 patients (3 with overlap syndrome and 2 with small-duct PSC) at a median time of 7 years after diagnosis. The 10-year posttransplant survival rate was 89%. CONCLUSIONS In one of the largest single-center studies of children with PSC, we found that most children with PSC had inflammatory bowel disease or autoimmune overlap and advanced fibrosis at diagnosis. Levels of alanine aminotransferase and gamma-glutamyl transferase were highest in patients with overlap syndrome and lowest in those with small-duct PSC. Levels of serum liver enzymes normalized after therapy with UDCA, including patients with positive autoimmune markers without histologic features of autoimmune hepatitis.

Brief Report: Deficits in Health Care Management Skills Among Adolescent and Young Adult Liver Transplant Recipients Transitioning to Adult Care Settings

OBJECTIVE The purpose of the present study was to describe and compare mastery of health care management in adolescent (aged 14-17 years) and young adult recipients of a liver transplant (age ≥ 18 years) expected to transfer from pediatric to adult care settings. METHODS Fifty-two liver transplant recipients completed the Developmentally Based Skills Checklist, which asks how often patients independently engage in specific health care management skills. RESULTS Overall, young adult patients reported greater health care management than adolescents. However, less than half of the young adults surveyed reported consistently managing their liver disease independently, making their own appointments, and understanding insurance issues. CONCLUSIONS Our results suggest that liver transplant recipients display inconsistency with regards to how frequently they engage in health management behaviors. Future work will address intervention development to remedy this first aspect of transition to adulthood such that patients are better prepared before moving to adult care centers.

Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults.

Arnon R, Annunziato R, Schilsky M, Miloh T, Willis A, Sturdevant M, Sakworawich A, Suchy F, Kerkar N. Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults.
Clin Transplant 2011: 25: E52–E60.

Liver transplantation in children with metabolic diseases: The studies of pediatric liver transplantation experience

Arnon R, Kerkar N, Davis MK, Anand R, Yin W, González‐Peralta RP for the SPLIT Research Group. Liver transplantation in children with metabolic diseases: The studies of pediatric liver transplantation experience.
Pediatr Transplantation 2010: 14:796–805.

Wilson disease in children: serum aminotransferases and urinary copper on triethylene tetramine dihydrochloride (trientine) treatment.

Objectives: To evaluate the efficacy of and adherence to trientine and/or zinc therapy in children with Wilson disease (WD). Materials and Methods: We retrospectively reviewed the clinical records of all children with WD in the pediatric liver/liver transplant program at our institution between 1998 and 2006. Results: A total of 22 children with WD were evaluated and treated. Seven with fulminant disease required liver transplantation and 15 were treated with trientine and/or zinc. Ten of those 15 had follow-up for 12 to 60 months and 6 of the latter 10 were followed for 12 to 18 months. All 10 patients were started on a trientine treatment regimen. Mean alanine aminotransferase (ALT) levels decreased from 183 ± 103 IU at presentation (n = 10) to 80 ± 46 IU at 12 months (n = 10) and 66 ± 40 IU at 18 months (n = 7). Mean 24-hour urinary copper levels increased from 156 μg at presentation to 494 μg at 1 to 2 months, then decreased to 71 μg after 21 to 24 months of treatment. Three of 10 patients had normalized ALT levels and 1 patient with cirrhosis continued with normal ALT levels since presentation. Four of 10 patients were documented to be nonadherent, as manifested by increased ALT levels (99 ± 31 IU); 1 patient had previously normalized ALT levels. In 3 of 10 patients, ALT level decreased but remained at an abnormal level (93 ± 53 IU). Conclusions: Trientine and/or zinc therapy is effective for children with WD. Nonadherence is a common cause of increased aminotransferase levels in patients with WD.

Adolescent transplant recipients as peer mentors: A program to improve self-management and health-related quality of life

The purpose of this study was to examine the safety, feasibility, acceptability, and preliminary efficacy of a cross‐age peer mentoring program created to improve adherence and psychosocial outcomes for pediatric liver transplant recipients. Twenty‐two participants were assigned to a “mentor now” or “mentor later” waitlist control group. Tacrolimus SD, a validated measure of adherence, was assessed for six months pre‐ and post‐intervention for both groups. Self‐report measures of self‐management and HRQOL were completed at recruitment and three months after training. Participant report indicated the acceptability of the intervention. Clinically significant improvement in adherence was detected. No significant changes on the psychosocial outcome measures at follow‐up were observed. This study demonstrated that an outpatient‐based mentoring program is a safe, feasible, and acceptable option to incorporate within a pediatric liver transplant program with potential for promising application in other transplantation populations as well. These results also suggest that the program may have been associated with meaningful improvement in adherence, although further evaluation is warranted.

An update on immunizations before and after transplantation in the pediatric solid organ transplant recipient

Abuali MM, Arnon R, Posada R. An update on immunizations before and after transplantation in the pediatric solid organ transplant recipient. 
Pediatr Transplantation 2011: 15: 770–777.

Adherence to medical recommendations and transition to adult services in pediatric transplant recipients

Purpose of reviewNonadherence to treatment recommendations, especially when associated with transition to adult care providers, account, by some estimates, for most organ rejections and death in long-term pediatric survivors of solid organ transplantations. It is therefore imperative that providers become familiar with the issues related to those major risks and ways to address them. Recent findingsIt is possible, and important, to routinely measure adherence to medications by using one of several available and proven methods of surveillance. There are numerous ways to improve adherence, and it is in fact possible to improve adherence and therefore outcomes in the transplant setting. The transition to adult services is a vulnerable period. The authors believe that it is possible to improve the transition process, and suggestions are presented in this review. However, solid research into interventions to improve transition is lacking. SummaryNonadherence to medical recommendations is prevalent and leads to poor outcomes following otherwise successful pediatric transplantation. An especially vulnerable period is the time when a recipient transitions to adult care. Routine monitoring of adherence, evaluating and addressing barriers to adherence, and collaborative, multidisciplinary care are all expected to substantially improve adherence and reduce the risks associated with transition.

Liver transplantation for hereditary tyrosinemia type I: Analysis of the UNOS database

Arnon R, Annunziato R, Miloh T, Wasserstein M, Sogawa H, Wilson M, Suchy F, Kerkar N. Liver transplantation for hereditary tyrosinemia type I: Analysis of the UNOS database.
Pediatr Transplantation 2011: 15: 400–405.