Helen M. Evans

Mycophenolate mofetil for renal dysfunction after pediatric liver transplantation

Background. Cyclosporine A (CsA) and tacrolimus (Tac) provide effective immunosuppression after orthotopic liver transplantation (OLT) but can cause renal dysfunction that may progress to end-stage renal failure (ESRF). Mycophenolate mofetil (MMF) is a newer immunosuppressant that does not affect renal function. Its long-term use in children with renal dysfunction after OLT has not yet been fully evaluated. Methods. A retrospective analysis was performed of all children begun on MMF for renal dysfunction and followed up for at least 1 year. Renal dysfunction was defined as calculated glomerular filtration rate (cGFR) of less than 65 mL/min/1.73 m2. cGFR and liver function were measured before and after transfer. Data were analyzed using the Wilcoxon signed rank test. Results. Forty-eight children (23 males) began MMF at a median age of 11.1 (0.9–18.1) years and at a median of 4.0 (0.3–12.4) years postOLT. Median baseline cGFR was 54 (range 29–65) mL/min/1.73 m2. Immunosuppression after transfer was MMF monotherapy in 36, MMF with steroids, in 4 and MMF with low-dose CsA or Tac in 8. In 44 (92%) patients, there was a statistically significant increase to a median cGFR of 69 (28–114) mL/min/1.73 m2 by 1 month and a further increase to a median cGFR of 77 (24–105) mL/min/1.73 m2 by 2 months of MMF treatment, after which time cGFR was maintained. Children aged less than 3 years at OLT or who were less than 5 years postOLT when MMF was begun demonstrated greater increases in cGFR. Four children with a median baseline cGFR of 34 (range 31–49) mL/min/1.73 m2 did not respond and progressed to ESRF. Mild side effects occurred in seven (15%) and gastrointestinal bleeding requiring discontinuation of MMF in one (2%). Liver function abnormalities occurred in seven (15%): transient transaminitis in three, acute rejection in two, and chronic rejection in two, of whom one required retransplantation. Conclusions. In 92% children with renal dysfunction after OLT, MMF treatment provided safe and effective immunosuppression and allowed CsA or Tac to be discontinued or reduced, leading to improvement of renal function. The improvement was greatest in younger children and those who began MMF early postOLT. Side effects were uncommon. Additional steroid cover during the transfer to MMF should be considered to prevent liver-allograft rejection.

Paracetamol-associated acute liver failure in Australian and New Zealand children: high rate of medication errors

Background In children, paracetamol overdose due to deliberate self-poisoning, accidental exposure or medication errors can lead to paediatric acute liver failure and death. In Australia and New Zealand, the nature of ingestion and outcomes of paracetamol-associated paediatric acute liver failure have not been described. Objective To describe the nature and outcomes of paracetamol-associated paediatric acute liver failure. Design Retrospective analysis of paracetamol-associated paediatric acute liver failure cases presenting 2002–2012. Setting New Zealand and Queensland Paediatric Liver Transplant Services. Results 14 of 54 cases of paediatric acute liver failure were attributed to paracetamol, the majority were secondary to medication errors. 12 of the 14 children were under the age of 5 years. Seven children received doses in excess of 120 mg/kg/day. Many of the other children received either a double dose, too frequent administration, coadministration of other medicines containing paracetamol or regular paracetamol for up to 24 days. Three children underwent transplant. One of these and one other child died. Conclusions In Australia and New Zealand, paracetamol overdose secondary to medication errors is the leading cause of paediatric acute liver failure. A review of regional safety practices surrounding paracetamol use in children is indicated.

Massive hepatic hemangioendothelioma and consumptive hypothyroidism.

Hypothyroidism was diagnosed in an infant with massive hepatic hemangioendothelioma. Markedly elevated serum reverse-triiodothyronine levels confirmed consumptive hypothyroidism. Large doses of thyroxine were initially required to normalise TSH. Thyroxine was tapered as the tumor regressed and was discontinued at 16 months old. Thyroid function remains normal without treatment.

Fatal and life threatening rupture of splenic artery aneurysms in children with portal hypertension

Abstract:  Aneurysms of the splenic artery (SAAs) are a rare complication of portal hypertension in adults. Although the risk of rupture is small, associated mortality is high. Furthermore, circulatory changes that occur following liver transplantation (OLT) may increase the risk of SAA rupture. The incidence in children with portal hypertension is unknown and thus we present our experience with two children who had ruptured SAA, one of whom died. Although there are no accepted methods for routine screening, hepatic angiography should be considered in children with long‐standing portal hypertension (more than 10 yr), in order to detect and consider resection of the aneurysms, either before or at the time of liver transplantation.

Acute fatty liver disease after suprasellar tumor resection.

Suprasellar tumors of the hypothalamus and pituitary gland, such as craniopharyngiomas, account for approximately 7% of intracranial tumors in childhood (1,2). The usual treatment is neurosurgical excision, and sequelae include pituitary dysfunction and hyperphagia with weight gain. Complications may occur before surgery as a result of the position of the tumor or after neurosurgical excision (2). Fatty liver disease is is now increasingly recognized in developed countries in relation to obesity, insulin resistance and type 2 diabetes mellitus (3). We present four cases of fatty liver that occurred acutely after excision of suprasellar tumors. In all cases, long-term evidence of fatty liver has been observed. One child developed cirrhosis with portal hypertension. This phenomenon has not previously been reported, and it highlights the need to monitor liver function in patients with suprasellar tumors.

Diagnostic utility of modified gliadin peptide antibody assays in New Zealand children.

Objective: The aim of the present study was to evaluate a panel of different antibody assays, including second-generation antigliadin kits, in a local paediatric population thought to be at risk for coeliac disease (CD). Methods: Seventy-nine children, who tested positive for immunoglobulin A (IgA) antibodies to tissue transglutaminase (TG), underwent duodenal biopsy. At endoscopy, serum was collected from all of the patients, and 9 different coeliac antibody assays were performed, both as isolated assays and in combination. These included immunoglobulin A (IgA) anti-tissue transglutaminase (TGA), and IgA plus IgG anti-deamidated gliadin peptide (DGPAG). A diagnosis of CD was made if the biopsies showed Marsh grade 3 lesions. Results: Twenty-four of 79 children had CD confirmed histologically. Only 39 of 79 were positive for Inova TGA, and 35 of 79 were positive for Inova DGPAG. Twenty-four of 39 who were TGA positive and 24 of 35 who were DGPAG positive had confirmed CD on biopsy. There was good correlation between TGA and DGPAG-positive predictive values. None of the modified gliadin tests produced false-negative results, and neither did the TGA. Conclusions: The Inova DGPAG and TGA assays have similar use in predicting CD in a selected paediatric population; however, in children who are positive for TGA when screened for CD, more than half have negative TGA serology when repeat testing is done at the time of biopsy. Those with persistent TGA positivity have only a 61.5% probability of having histologic CD, compared with 68.6% of those children positive for DGPAG.

Long-term follow up of paediatric liver transplant recipients: outcomes following transfer to adult healthcare in New Zealand.

Poor outcomes are reported in young people with chronic health conditions. We performed a retrospective notes review of New Zealand paediatric liver transplant recipients transferred to adult services. Two patients were lost to follow up. Out of 20, 12 were non‐adherent, and out of 12, 7 developed rejection. Other risk behaviours were common in the non‐adherent group. We conclude that dedicated services for these young people may be needed to optimise outcomes.

Capacity building in pediatric transplant infectious diseases: an international perspective

Transplant infectious diseases is a rapidly emerging subspecialty within pediatric infectious diseases reflecting the increasing volumes and complexity of this patient population. Incorporating transplant infectious diseases into the transplant process would provide an opportunity to improve clinical outcome and advocacy as well as expand research. The relationship between transplant physicians and infectious diseases (ID) specialists is one of partnership, collaboration, and mutual continuing professional education. The ID CARE Committee of the International Pediatric Transplant Association (IPTA) views the development and integration of transplant infectious diseases into pediatric transplant care as an international priority.

Hodgkin disease relapse discovered at the time of liver transplant for acute liver failure

Hope BC, Chau KY, Evans HM, Mouat S, Munn S, Yeong ML, Chin SE. Hodgkin disease relapse discovered at the time of liver transplant for acute liver failure. 
Pediatr Transplantation 2012: 16: E10–E14.

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.