Survivors Of Pediatric Liver Transplantation Research Articles

Markers of obesity in Danish pediatric liver transplantation recipients.

Long-time survivors of pediatric liver transplantation have an increased incidence of the metabolic syndrome. Adult recipients have an increased risk of post-transplantation obesity; however, pediatric data are limited. The study included 42 recipients of pediatric liver transplantation in Denmark, transplanted between 1990 and 2014. The study participants were examined with anthropometric measures, dual-energy X-ray scans and blood samples. From the anthropometric measures, body mass index (BMI) and BMI standard deviation score (SDS) were calculated. From the dual-energy X-ray scans, fat percent was assessed, and body fat mass index (BFMI) was calculated. The median age was 17.4 years (range 4.1-38.9) at the time of the study, and the median time since transplantation was 8.5 years (range 0.4-23.9). The prevalence of overweight and obesity was 31.0% based on BMI SDS (age below 18) and BMI (age 18 and above). When compared to the participants with normal weight, the participants with overweight and obesity had a higher BFMI (9.29 vs 5.57 kg/m2 , p< .001) and fat percent (38.35% vs 29.50%, p= .006). They had higher levels of total cholesterol (4.3 vs 3.6 mmol/L, p= .023) and low-density lipoprotein (2.5 vs 1.7, p= .015), and had had longer time since transplantation (15.6 vs 8.5 years respectively, p= .045). Long-time survivors of pediatric liver transplantation have a higher BMI or BMI SDS than the general pediatric population. The obesity is characterized by a higher BFMI, fat percent, and cholesterols levels, when compared to recipients without overweight or obesity.

Liver transplant and quality of life in the pediatric population: a review update (2013-2014).

Liver transplantation is emerging as the treatment of choice for children with end-stage liver disease and some cases of acute liver failure. Owing to improvements in the surgical and medical management of liver transplantation, most patients survive surgery and do well physically in the posttransplant period. However, quality of life (QOL) for these children remains below expectation and is associated with poor psychological and social functioning. In this article, we review the recent literature and provide an opinion regarding QOL in pediatric liver transplant (PLT) patients and possible interventions to optimize it. We reviewed articles published in 2013 and 2014 reporting QOL in PLT survivors. Our review of the literature suggests that children undergoing liver transplantation have varying degrees of QOL in the post transplantation period despite improvements in medical and surgical managements. It is important to proactively identify and address psychological difficulties in patients and their families prior to transplant. Following transplantation, a multidisciplinary approach to targeting rehabilitation and decreasing negative effects of the transplant may assist with improving the QOL for patients and their families.

Sustained linear growth and preserved renal function in 10-year survivors of pediatric liver transplantation.

The aim of this study was to characterize the clinical outcomes of children and adolescents who achieved survival of more than 10 years following liver transplantation (LT) in a single center in Korea. From June 1996 to October 2003, 57 pediatric LTs were performed. The medical records of 44 patients who had survived more than 10 years were reviewed retrospectively. Median age of patients at LT was 0.8 years. Forty-one patients received living donor LT, and three patients received deceased donor LT. Biliary atresia was the most common indication (65.9%). Thirty-five patients were on tacrolimus monotherapy at 10 years post-LT with a mean trough level of 2.73 ng/ml, and five patients were maintaining stable graft function without any immunosuppression. There were no patients receiving antihypertensive medication and one case of diabetes mellitus. Renal dysfunction was seen in two patients (4.5%), while none required renal replacement therapy. Mean height z-score prior to LT was -1.35 and at 10 years post-transplant was 0.05. Good linear growth was sustained in this cohort throughout the 10 years, approaching the 50th percentile. Also, there were remarkably low incidences of renal dysfunction and patients requiring medications for glycemic or hypertensive control, all hallmarks of continued use of immunosuppressive agents.

Cardiovascular risk factors and cardiac disorders in long-term survivors of pediatric liver transplantation.

The MetS and cardiovascular disease are leading causes of late morbidity in adult liver transplantation recipients; however, limited data are available in pediatric liver transplantation. A single-center retrospective review was undertaken for patients who had a liver transplantation before 18yr of age and were >5yr post-transplantation, to study the prevalence of MetS, its components, and cardiac disorders. Fifty-eight patients were included in the study with a mean age at transplantation of 6.3±6.1yr and mean follow-up of 14.1±6.0yr. Of the study group, 41.4% were overweight or obese, with ongoing prednisone use and increased duration of follow-up being significant risk factors. Fifty-three patients had sufficient data for determining MetS, which was present in 17% of the patients. Although the prevalence of MetS is low in pediatric liver transplant recipients, it is associated with CKD and prednisone therapy (p<0.05). Echocardiography data were available for 23 patients, of whom 43.4% had LVH and 13% had evidence of PH. The spectrum of cardiac disorders in this population is much wider than in adults.

Pediatrics.

Introduction: The metabolic syndrome and cardiovascular (CV) disease have emerged as leading causes of late morbidity in adult liver transplantation recipients; however, limited data are available in pediatric liver transplantation (PLT). The aim of our study was to examine the prevalence of metabolic syndrome, its components, and cardiac disorders in PLT patients who survived for more than 5 years. Methods: A single-center retrospective review of demographics, clinical, laboratory and echocardiographic parameters was undertaken at the time of last follow-up for patients who had a liver transplantation before 18 years of age and more than 5 years post-transplantation. Results: Fifty-eight patients were included in the study with a mean age at transplantation of 6.3 ± 6.1 years and mean follow-up of 14.1 ± 6.0 years. Of the study group, 24 patients (41.4%) were overweight or obese and 9 patients (17%) met the definition for metabolic syndrome (Figure 1). Echocardiography data was available for 23 patients; of whom 10 patients (43.4%) demonstrated left ventricular hypertrophy and 3 patients (13%) had evidence of pulmonary hypertension (mean estimated pulmonary artery systolic pressure of 46.4 ± 8.5 mm Hg in those elevated). A statistically significant association between steroid intake and metabolic syndrome was found (p<0.05). Other cardiac disorders included hepato-pulmonary syndrome, cirrhotic cardiomyopathy, tacrolimus-associated cardiomyopathy, and moyamoya vascular pattern.Figure 1: Individual criteria met for metabolic syndrome.Conclusion: Metabolic syndrome and its components are prevalent among patients after PLT during long-term follow-up. Routine echocardiography during long-term follow up of PLT patients may be helpful in identifying left ventricular hypertrophy and pulmonary hypertension. The spectrum of CV complications in this population is much wider than in adults.

Withdrawal of immunosuppression following pediatric liver transplantation: a Markov analysis.

Survivors of pediatric liver transplantation are at risk for developing complications related to posttransplant immunosuppressive medications. Withdrawal is possible in selected patients but carries the risk of graft rejection and loss. We modeled the effect of withdrawing immunosuppressive medications on survival, cost, and quality-adjusted life-years (QALYs) in a hypothetical cohort of pediatric patients who received transplantation for biliary atresia with stable liver enzymes and no recent episodes of rejection, and who were free from immunosuppression-related adverse effects. A decision analysis tree was developed, and Monte Carlo simulations were used to track patients through the model during a 10-year time course with 1-year cycles. Data from the literature were used to assign probabilities to major clinical events and preference-based utility scores to the values of health outcomes. One-way and probabilistic sensitivity analyses were used to evaluate the impact of uncertainty. Patients following the withdrawal strategy had a 10-year survival rate of 95.8% and experienced 8.61 QALYs versus 88.6% survival and 8.01 QALYs for those taking immunosuppressive medications. Each additional QALY is attained at a cost of -$18,992.41 and was therefore cost saving. Patients in our model who had their immunosuppression withdrawn had improved survival and QALYs with lower costs. Although every effort was made to validate the model, it is limited by the accuracy of the underlying assumptions. Therefore, clinical trials are needed to determine predictors of successful immunosuppression withdrawal to allow for personalization of medication regimens.

Cholesterol Metabolism Altered and FGF21 Levels High After Pediatric Liver Transplantation Despite Normal Serum Lipids

Liver transplantation (LT) predisposes to metabolic derangements and increases the risk for cardiovascular disease. We conducted a national cross-sectional study of all pediatric recipients who underwent LT between 1987 and 2007. We measured serum levels of noncholesterol sterols (surrogate markers of cholesterol synthesis and intestinal absorption) and fibroblast growth factor 21 (FGF21) in 49 patients (74% of survivors) at a median of 10 years posttransplant and in 93 controls matched for age and gender. Although serum cholesterol levels were similar in patients and controls, patients displayed increased whole-body synthesis and decreased intestinal absorption of cholesterol compared with controls (lathosterol to cholesterol ratio 129 ± 55 vs. 96 ± 41, respectively, p < 0.001; campesterol to cholesterol ratio 233 ± 91 vs. 316 ± 107, respectively; p < 0.001). Azathioprine (r =-0.383, p = 0.007) and low-dose methylpredisolone (r =-0.492, p < 0.001) were negatively associated with lathosterol/sitosterol ratio reflecting a favorable effect on cholesterol metabolism. FGF21 levels were higher in patients than in controls (248 pg/mL vs. 77 pg/mL, p < 0.001). In healthy controls, FGF21 was associated with cholesterol metabolism, an association missing in LT recipients. Normal serum lipids are achievable in long-term survivors of pediatric LT, but changes in cholesterol metabolism and increased FGF21 levels may explicate later cardiovascular risk.

Blood Pressure Elevation in Long-Term Survivors of Pediatric Liver Transplantation

As pediatric liver transplant (LT) recipients come of age, additional insight into long-term medical complications of immunosuppression is warranted. The aims of this study were to estimate the prevalence of elevated blood pressure (BP) in long-term survivors of pediatric LT using the data from the Studies in Pediatric Liver Transplantation (SPLIT) database and to identify predictive factors. Patients enrolled in the BP arm of the SPLIT cohort participated in the study. All patients were of at least 5 years but ≤10 years post-LT. Automated BP measurements were obtained at anniversary visits. BP measures were classified as normal, borderline or elevated according to standard criteria. Patients taking antihypertensive medications were classified as "elevated." Eight hundred and fifteen patients participated. The prevalence of elevated BP measurements 5 to 10 years post-LT was 17.5 to 27.5%. Of total 62.5% patients presented with at least one additional elevated BP at a later follow up visit. Multivariate analysis revealed the following parameters to be predictive of elevated BP: age at transplant, steroid use at last BP measurement and cGFR at last BP measurement. Pediatric LT patients show a high prevalence of elevated BP measurements 5 to 10 years following LT, which is related to age at LT, decreased cGFR and recent steroid use.

Outcomes of 5-Year Survivors of Pediatric Liver Transplantation: Report on 461 Children From a North American Multicenter Registry

Although liver transplantation has been the standard of care therapy for life-threatening liver diseases for >20 years, data on the long-term impact of liver transplantation in children have been primarily limited to single-center experiences. The objective of this study was to characterize and evaluate the clinical course of children who have survived >or=5 years after pediatric liver transplantation in multiple centers across North America. Patients enrolled in the Studies of Pediatric Liver Transplantation database registry who had undergone liver transplantation at 1 of 45 pediatric centers between 1996 and 2001 and survived >5 years from liver transplantation were identified and their clinical courses retrospectively reviewed. The first graft survival for 461 five-year survivors was 88%, with 55 (12%) and 10 (2%) children undergoing a second and third liver transplantation. At the 5-year anniversary clinic visit, liver function was preserved in the majority with daily use of immunosuppression therapy, including a calcineurin inhibitor and oral prednisone, reported by 97% and 25% of children, respectively. The probability of an episode of acute cellular rejection occurring within 5 years after liver transplantation was 60%. Chronic rejection occurred in 5% patients. Posttransplant lymphoproliferative disease was diagnosed in 6% children. Calculated glomerular filtration rate was <90 mL/minute per 1.73 m2 in 13% of 5-year survivors. Age- and gender-adjusted BMI>95th percentile was noted in 12%, with height below the 10th percentile in 29%. Children who are 5-year survivors of liver transplantation have good graft function, but chronic medical conditions and posttransplantation complications affect extrahepatic organs. A comprehensive approach to the management of these patients' multiple unique needs requires the expertise and commitment of health care providers both beyond and within transplant centers to further optimize long-term outcomes for pediatric liver transplant recipients.

Graft histology characteristics in long-term survivors of pediatric liver transplantation

The factors that influence the long-term histological outcome of transplanted liver allografts in children are not yet fully understood, and the role of surveillance biopsies in patients with normal graft function remains controversial. The aims of this study were to describe the long-term graft histology of pediatric liver transplant recipients surviving at least 3 years and to analyze factors correlating with long-term histological outcome. Histological slides of 63 long-term liver transplant recipients were assessed for inflammation and fibrosis. The histological findings were correlated with clinical, biochemical, serological, and radiological findings. A significant proportion of biopsies from these patients showed some type of histological abnormalities, with fibrosis being observed in 61 (97%) patients. Duration of transplantation of >6 years and > or =grade 2 inflammation were significantly associated with advanced fibrosis. We could not identify any correlation between > or =stage 3 fibrosis and donor age, cold and warm ischemia time, history of de novo autoimmune hepatitis, hepatic artery thrombosis, chronic rejection, or alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase values. In conclusion, liver fibrosis appears to be a common finding in long-term pediatric liver transplant survivors. The cause of this fibrosis is uncertain, and normal alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels do not exclude the presence of significant fibrosis.

Assessment and management of psychosocial challenges in pediatric liver transplantation

Assessment and management of psychosocial challenges in pediatric liver transplantation

Understanding quality of life for children after liver transplantation: A work in progress

Understanding quality of life for children after liver transplantation: A work in progress

Academic outcome in long-term survivors of pediatric liver transplantation.

Fifty long-term (3-9 year) survivors of pediatric liver transplantation were assessed using IQ, achievement, and school history measures. Forty-seven of these children had been evaluated before transplantation on intellectual measures, with mean scores for the group found to be in the low average range. At follow-up evaluation, the scores remained in the low average range on all intellectual measures; performance on academic tests was also within the low average range. Thirteen children (26%) were classified as having learning problems based on discrepancies between intellectual and academic function, but only five of them (38%) had received special education services. Nine of the children (18%) had IQ scores less than 70. Academic outcome did not relate to diagnosis, time between diagnosis and transplantation, age at time of transplantation, or average levels of cyclosporin A. Careful assessment and appropriate special education services are indicated to optimize the educational outcome of children who survive liver transplantation.