Cyclosporine monitoring in the early post-transplant period in pediatric liver transplant recipients.

UNLABELLED: Monitoring of CsA blood levels two h post-dose (C2) has shown a higher correlation to drug exposure than monitoring of trough levels (C0) at least in adults, but initial doses and target blood levels of CsA have yet to be established in pediatric transplant patients. The objectives of the study were to describe the pharmacokinetics of CsA administered by NGT in the first days after transplantation and the dose of Sandimmun Neoral required to achieve minimum therapeutic range blood levels. This study included 20 pediatric liver transplant recipients (mean age of 3.2 yr) treated with CsA administered by NGT from day one post-transplant until they were able to ingest oral medication. The study was continued until one yr of post-transplant follow-up. Eight h pharmacokinetic profiles were performed on days one, three, and five post-transplant to determine the minimum dose required to achieve the therapeutic range. All children received an initial dose of 15 mg/kg/day of CsA by NGT. Mean CsA doses administered on days one, three, and five were 16.8, 29.5, and 36.5 mg/kg/day, respectively. Mean C0 levels of 119, 310, and 337 ng/mL and mean C2 levels of 213, 753, and 888 ng/mL were obtained. No correlation was found between C0 and C2 levels and the AUC(0-8 h). Intravenous administration of CsA was required in 55% of patients. The biopsy-confirmed acute rejection rate was 45%, with graft and patient survival rates of 95 and 100%, respectively. CONCLUSIONS: Poor absorption of CsA in small children requires a considerable increase in dose. CsA exposure cannot be estimated by single C0 or C2 determinations in the early post-transplant period.

[Crigler-Najjar syndrome: diagnosis and treatment]. / Síndrome de Crigler-Najjar: diagnóstico y tratamiento.

INTRODUCTION: Crigler-Najjar syndrome (CNS) is a very rare disease characterized by severe indirect hyperbilirubinemia from birth with normal liver function. It may cause kernicterus at any age. This disease is due to a total or partial deficiency of the UDP-glucuronosyltransferase enzyme caused by a mutation of the five exons of the ULT1A1 gene. PATIENTS AND METHODS: We reviewed the clinical outcomes of 7 children diagnosed with CNS between 1987 and 2004. RESULTS: There were three boys and four girls (two of which were homozygote twins). Two children had familial consanguinity. Three out of the six families had another healthy child. The mean follow-up was 8.3 years (14 months-17 years). In all patients, jaundice was detected in the first 3 days of life. The children were admitted to hospital between the fourth and the sixtieth day of life with jaundice and indirect bilirubin levels of between 12.5 and 32 mg/dl. In all patients, hemolysis was ruled out and hepatic function was normal. The diagnosis was based on genetic study in 4 patients, on inactive UGT enzyme in liver in 1 patient, and on clinical features exclusively in 2 patients. Treatment consisted of phenobarbital and phototherapy from 8 to 16 hours a day in all patients except three. Associated calcium salts were found in 5 patients and cholestyramine was found in two. Two patients developed kernicterus. Two underwent liver transplantation and bilirubin levels became normal. The remaining patients maintained indirect bilirubin from 15 to 25 mg/dl with no associated neurological alterations. CONCLUSIONS: Patients with CNS are at greater risk of developing kernicterus, mostly associated with indirect bilirubin levels of around 25 mg/dl. Phototherapy is very useful in these patients but the only definitive treatment is liver transplantation.

Síndrome de Crigler-Najjar: diagnóstico y tratamiento / Crigler-Najjar syndrome: diagnosis and treatment

Introducción El síndrome de Crigler-Najjar (SCN) es una entidad infrecuente, caracterizada por hiperbilirrubinemia indirecta grave desde el nacimiento con función hepática normal, y que puede ocasionar querníctero a cualquier edad. Se debe a un déficit total o parcial de la enzima UDP-glucuroniltransferasa (UGT) causado por mutaciones en los exones del gen UGT1A1. Pacientes y métodos Se revisa la evolución de 7 niños, diagnosticados de SCN, de 1987 a 2004. Resultados Los pacientes son 3 niños y 4 niñas, dos de ellas gemelas homozigotas. En 2 familias existía consanguinidad y en tres los hermanos eran sanos; el resto eran hijos únicos. El seguimiento medio fue de 8,3 años (14 meses-17 años). La ictericia fue detectada en todos en los primeros 3 días de vida. El ingreso que motivó la sospecha diagnóstica ocurrió entre el día 4 y el 60 con cifras de bilirrubina indirecta (BI) de entre 12,5 y 32 mg/dl. En todos se descartó hemólisis y la función hepática fue normal. El diagnóstico se basó en un estudio genético de 4 casos, en determinación de 0 % de la actividad de la enzima UGT en hígado en uno y en criterios clínicos exclusivamente en los dos restantes. El tratamiento consistió en fenobarbital y fototerapia de 8 a 16 h diarias en todos excepto en tres. En 5 casos se asociaron sales de calcio y en dos colestiramina. Un total de 2 pacientes desarrollaron querníctero durante la evolución; 2 niños fueron trasplantados con normalización del metabolismo de la bilirrubina. El resto presentaron cifras de BI de entre 15 y 25 mg/dl sin desarrollar alteraciones neurológicas. Conclusiones El principal riesgo de los pacientes con SCN es el desarrollo de querníctero, sobre todo con cifras de BI en torno a 25 mg/dl. La fototerapia es útil en el control de estos pacientes. El trasplante hepático es el único tratamiento definitivo

Introduction Crigler-Najjar syndrome (CNS) is a very rare disease characterized by severe indirect hyperbilirubinemia from birth with normal liver function. It may cause kernicterus at any age. This disease is due to a total or partial deficiency of the UDP-glucuronosyltransferase enzyme caused by a mutation of the five exons of the ULT1A1 gene. Patients and methods We reviewed the clinical outcomes of 7 children diagnosed with CNS between 1987 and 2004. Results There were three boys and four girls (two of which were homozygote twins). Two children had familial consanguinity. Three out of the six families had another healthy child. The mean follow-up was 8.3 years (14 months-17 years). In all patients, jaundice was detected in the first 3 days of life. The children were admitted to hospital between the fourth and the sixtieth day of life with jaundice and indirect bilirubin levels of between 12.5 and 32 mg/dl. In all patients, hemolysis was ruled out and hepatic function was normal. The diagnosis was based on genetic study in 4 patients, on inactive UGT enzyme in liver in 1 patient, and on clinical features exclusively in 2 patients. Treatment consisted of phenobarbital and phototherapy from 8 to 16 hours a day in all patients except three. Associated calcium salts were found in 5 patients and cholestyramine was found in two. Two patients developed kernicterus. Two underwent liver transplantation and bilirubin levels became normal. The remaining patients maintained indirect bilirubin from 15 to 25 mg/dl with no associated neurological alterations. Conclusions Patients with CNS are at greater risk of developing kernicterus, mostly associated with indirect bilirubin levels of around 25 mg/dl. Phototherapy is very useful in these patients but the only definitive treatment is liver transplantation

Hepatitis B. Hepatitis crónica.Evolución y tratamiento / Hepatitis B. Chronic hepatitis. Outcome and treatment

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