Sirolimus to treat chronic and steroid-resistant allograft rejection-related fibrosis in pediatric liver transplantation.

This study aimed to report our experience with the use of sirolimus in pediatric liver transplant patients with chronic rejection or steroid-resistant rejection with hepatic fibrosis, focusing on their histological evolution. All pediatric liver transplant recipients who received off-label treatment with sirolimus for chronic ductopenic rejection or cortico-resistant rejection between July 2003 and July 2022 were included in the study. All nine patients included in the study showed improvement in liver enzymes and cholestasis parameters as soon as 1-month after postsirolimus introduction. A decrease in fibrosis stage was observed in 7/9 (77.7%) patients at 36 months. All but one patient experienced an improvement in the Rejection Activity Index and ductopenia at 12 months. A single patient had to discontinue sirolimus treatment owing to nephrotic proteinuria. In conclusion, sirolimus may be a safe and effective treatment for chronic and steroid-resistant rejection and may improve allograft rejection-related fibrosis and ductal damage.

Factors affecting catch-up growth after liver transplantation.

BACKGROUND: The reported incidence of catch-up growth following orthotopic liver transplantation (OLT) ranges widely, from 0% to 97%. OBJECTIVE: We undertook bivariate analysis of multiple factors that might affect post-OLT growth in children undergoing OLT, and described the results with different parameters used to determine catch-up growth. METHODS: Eighty patients met the inclusion criteria. RESULTS: Catch-up growth occurred in 14% during the first 6 months, 15% at 1 year, 39% at 2 years, 16% between 3 and 6 years, and 16% after 6 years post-OLT. The earlier catch-up growth was shown in metabolic diagnosis, patients over 10 years old and those without steroids at 1 year post-OLT. CONCLUSIONS: It is difficult to determine an acceptable definition of catch-up growth. We suggest that Zvel score > or =0 is the best parameter to evaluate catch-up growth, since the results are more normally distributed. Patients with prednisone withdrawal later than 1 year post-OLT and those with diagnosis of hepatitis and cirrhosis showed the slowest catch-up growth.

Two- to three-fold increase in blood tacrolimus (FK506) levels during diarrhea in liver-transplanted children.

BACKGROUND: The diagnosis and treatment of diarrhea in liver transplant recipients often pose a challenge owing to the variety of infectious and non-infectious causes. However, diagnosis is principally focused on ruling out an infectious etiology. Tacrolimus, an immunosuppressive agent generally used after liver transplantation, is absorbed mainly from the duodenum through the upper jejunum. It can be assumed that metabolism of the drug will be influenced by diarrhea. METHODS: Four liver transplant recipients who developed an episode of acute gastroenteritis. Infectious etiology was confirmed; trough tacrolimus levels were measured before, during and after gastroenteritis. RESULTS: All patients presented a two- to three-fold increase in blood tacrolimus levels after the onset of gastroenteritis. CONCLUSIONS: Until the role played by the intestine in the metabolism of tacrolimus is fully understood, it is prudent to recommend early dose reduction of tacrolimus and careful monitoring of trough levels during diarrheal disorders of any nature in pediatric liver-transplanted patients.

[Acute liver failure due to T cell lymphoma without hepatic infiltration]. / Insuficiencia hepática aguda por linfoma de células T sin infiltración hepática.

Hepatomegaly and alterations in hepatic function are common to all patients with sickle-cell disease. In these patients, hepatic sickling is a manifestation of severe intrahepatic vaso-oclusive crises, even at levels of 25 % HbS and hematocrits of more than 45-50 %, which in 10 % of cases can lead to acute hepatic failure (AHF). AHF can be due to a variety of causes, including hematologic malignancies, but T cell lymphoma, which is usually secondary to diffuse hepatic infiltration and ischemia, is an exceptional cause, although other mechanisms can be involved. Cytokines released by lymphomas have recently been implicated as a cause of AHF.We describe a black girl with sickle cell disease, who developed AHF due to T cell lymphoma without lymphomatous infiltration of the liver. The only mechanism found to explain the clinical findings was release of cytokines by lymphoma. In patients with AHF of unknown etiology we propose early liver biopsy, because prognosis depends on the presence or absence of hepatic tumour infiltration. If AHF develops in a patient with diagnosed malignant disease, cytokine release may be the cause of AHF. Consequently, early diagnosis of the underlying disease and provision of liver support, as well as direct removal of inflammatory mediators from the circulation by exchange transfusion or other methods, should be the main priorities.

Insuficiencia hepática aguda por linfoma de células T sin infiltración hepática / Acute liver failure due to T cell lymphoma without hepatic infiltration

En pacientes con anemia de células falciformes, la hepatomegalia y alteración de la función hepática son comunes. En ellos, las crisis vasooclusivas intrahepáticas graves, pueden ocurrir con niveles de hemoglobina del 25 per cent y hematocrito superior a 45-50 per cent. Un 10 per cent pueden llegar a fallo hepático agudo (FHA). El FHA tiene diversas causas, entre ellas los procesos hematológicos malignos, excepcionalmente el linfoma de células T, que por lo general produce infiltración hepática e isquemia, aunque éste no es el único mecanismo lesional. Recientemente se ha considerado a las citocinas liberadas por linfomas como causa de FHA. Se presenta el caso de una niña de raza negra, con enfermedad de células falciformes, que presentó FHA secundario a un linfoma de células T que no infiltró al hígado, y donde el único mecanismo que se encontró para explicar el cuadro clínico fue el mediado por las citocinas. Cuando los estudios de imagen no confirman la infiltración hepática por células malignas, debe valorarse realizar una biopsia hepática, pues el pronóstico del FHA variará en función de si hay o no infiltración tumoral. Si la causa del FHA es compatible con una enfermedad neoplásica, las citocinas pueden ser las responsables del FHA. Por ello, establecer medidas de soporte de la función hepática e iniciar tratamiento precoz de la enfermedad de base, además de remover directamente estos mediadores inflamatorios de la circulación mediante exanguinotransfusión u otro procedimiento debe constituir la principal preocupación (AU)