Pediatr Transplantation 2014: 18: 177–184

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Pediatric Transplantation DOI: 10.1111/petr.12218

Risk factors for neurological complications and their correlation with survival following pediatric liver transplantation Lee YJ, Yum M-S, Kim E-H, Choi H-W, Oh SH, Kim DY, Kim KM, Ko T-S. Risk factors for neurological complications and their correlation with survival following pediatric liver transplantation.

Yun Jeong Lee1*, Mi-Sun Yum1*, Eun-Hee Kim1, Hae-Won Choi1, Seak Hee Oh1, Dae Yeon Kim2, Kyung Mo Kim1 and Tae-Sung Ko1

Abstract: Despite the improved outcomes of LT, post-operative NCs remain a significant cause of morbidity and mortality. The aim of the study was to identify the incidence of and risk factors for NCs in children who underwent LT. The medical records of pediatric patients who underwent LT at Asan Medical Center Children’s Hospital between January 1994 and December 2010 were retrospectively analyzed. The onset and types of NC and pretransplant variables associated with NC were evaluated. We identified 190 children (85 boys [44.7%], 105 girls [55.3%]) of mean age 4.1  4.7 yr, who underwent LT. Forty-six NCs occurred in 41 (21.6%) patients after LT, the most common being seizures (n = 13, 28.3%) and encephalopathy (n = 10, 21.7%). Of the 46 NCs, 24 (52.2%) occurred within three months after LT. Multivariate analysis showed that primary liver disease, preoperative neurological problems, preoperatively higher serum creatinine concentration, and graft failure were significant risk factors for NCs. The survival rate was significantly lower for patients with NCs than for those without (p < 0.001). NCs after pediatric LTs were common and associated with a higher mortality rate in our study. Close monitoring and appropriate risk management may improve the longterm outcomes of pediatric patients who undergo LT.

1

LT is the only successful treatment modality for pediatric patients with end-stage liver disease. Advances in surgical techniques, post-operative management, and the appropriate use of immunosuppressants have enhanced patient and graft survival following pediatric LT (1, 2). Many of these LT recipients, however, experience complications and reduced long-term quality of life. NCs after pediatric LT have been reported in 8–46% of patients, with high morbidity and Abbreviations: ADHD, attention deficit hyperactivity disorder; AED, antiepileptic drug; ALF, acute liver failure; BA, biliary atresia; BP, blood pressure; CI, confidence interval; CMV, cytomegalovirus; CNS, central nervous system; CT, computed tomography; EEG, electroencephalography; HB, hepatoblastoma; HR, hazard ratio; HTN, hypertension; IN, immunosuppressant neurotoxicity; LC, liver cirrhosis; LT, liver transplantation; MRI, magnetic resonance imaging; NC, neurological complication; PRES, posterior reversible encephalopathy syndrome; TPN, total parenteral nutrition; UCD, urea cycle disorder.

Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea, 2Department of Pediatric Surgery, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea Key words: liver transplantation – neurological complication – immunosuppressive treatment – children Tae-Sung Ko, M.D., Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, 388-1, Pungnap-dong, Songpa-gu, Seoul, 138-736, Korea Tel.: 82 2 3010 3390 Fax: 82 2 473 3725 E-mail: [email protected] *These two authors contributed equally. Accepted for publication 2 December 2013

mortality rates (3–6). Several studies report that NC rates are higher, and complications are more severe in pediatric than in adult patients (7). Although the causes of NCs are not clear, studies suggest that use of immunosuppressants, graft dysfunction, preoperative hepatic encephalopathy, and electrolyte and metabolic derangements are involved. As the indications for LT in children differ from those in adults, different types of NCs and different risk factors for NCs are expected. More than 200 successful pediatric LTs have been performed in our center (8). Based on this clinical experience, we assessed the incidence and type of NCs and evaluated risk factors for NCs in pediatric patients undergoing LT. Methods The medical records of all children (age 20 ng/mL or cyclosporine >400 ng/mL), or as an improvement in a neurologic event after modifying the dose of immunosuppressant. All patients received comedication, including prophylactic CMV medication (gancyclovir or acyclovir), trimethoprim/sulfamethoxazole, ulcer prophylaxis (H2-blocker or antiacid) and an antifungal agent. All patients were followed up until August 2012 or death.

Statistical analysis Categorical variables in patients with and without NCs were compared using chi square tests, and continuous variables were compared using Student’s t-tests. Survival was evaluated using the Kaplan–Meier method and compared using the log-rank test. A Cox proportional hazards model was used to identify the risk factors for NCs in these patients. Variables selected by univariate analysis (p < 0.20) were evaluated in multivariable analysis using backward elimination. All tests were two sided, and p < 0.05 was considered statistically significant. Analyses were performed using SPSS 18.0 for Windows (SPSS, Inc., Chicago, IL, USA).

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Results

A review of the medical records of our center identified 193 children, aged

Risk factors for neurological complications and their correlation with survival following pediatric liver transplantation.

Despite the improved outcomes of LT, post-operative NCs remain a significant cause of morbidity and mortality. The aim of the study was to identify th...
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