The relation between activator and inhibitor killer-cell immunoglobulin-like receptors and hepatotoxicity in oncological treatment.

BACKGROUND: The molecular interactions between killer-cell immunoglobulin-like receptors (KIRs) and their related HLA class I ligands play a central role in regulating the responses of natural killer (NK) cells. Our study aim was to determine the role played by KIR genes and their HLA ligands in the genetic predisposition for the development of hepatotoxicity in children treated with chemotherapy for an oncological process. METHODS: The study group was composed of 22 children with cancer, being treated with chemotherapy at the Unit of Pediatric Oncology of the Maternity Hospital Virgen de las Nieves (Granada, Spain) and presenting signs of drug-induced liver injury (DILI). Twenty-four children receiving similar treatment but presenting no signs of DILI were selected as a control group. RESULTS: The children with the KIR K2DS2 were four times more likely to have hepatotoxicity (OR=4.08, P=0.034, 95% CI: 1.1-15). The patients with 2DS2 and the C1 ligand were ten times more likely to undergo an episode of hepatotoxicity (P=0.007). CONCLUSIONS: KIRs may be risk factors for susceptibility to hepatotoxicity following chemotherapy.

Killer immunoglobulin-like receptor and cancer.

INTRODUCTION: Natural killer (NK) cells play an important role in defense against tumor cells. The development and function of NK cells is governed by a dynamic balance between inhibition and activation of cell surface receptors, including KIR receptors. PATIENTS AND METHOD: A case-control study is carried out that compares a group of 46 children diagnosed with malignant diseases, the control group is made up of 82 healthy children. KIRs genes, haplotypes and ligands were determined and compared between groups. RESULTS: There are no differences in KIRs genes, KIRs haplotypes or in KIRs gene ligands between groups. However, when KIRS and ligands were jointly studied, k2DS1_C2 was significantly higher in the group of cancer children (p=0.016). CONCLUSIONS: Our results do not provide evidence of an association between pediatric cancer disease with genotypes and groups of genes KIRs. The k2DS1_C2 genotype could predispose to susceptibility to malignant processes in children.

[Killer immunoglobulin-like receptor and cancer]. / Estudio de casos y controles de los receptores de tipo KIR (killer inmunoglobulin-like receptor) en oncología.

INTRODUCTION: Natural killer (NK) cells play an important role in defense against tumor cells. The development and function of NK cells is governed by a dynamic balance between inhibition and activation of cell surface receptors, including KIR receptors. PATIENTS AND METHOD: A case-control study is carried out that compares a group of 46 children diagnosed with malignant diseases, the control group is made up of 82 healthy children. KIRs genes, haplotypes and ligands were determined and compared between groups. RESULTS: There are no differences in KIRs genes, KIRs haplotypes or in KIRs gene ligands between groups. However, when KIRS and ligands were jointly studied, k2DS1_C2 was significantly higher in the group of cancer children (p̊=̊0.016). CONCLUSIONS: Our results do not provide evidence of an association between pediatric cancer disease with genotypes and groups of genes KIRs. The k2DS1_C2 genotype could predispose to susceptibility to malignant processes in children.

Lesión hepática inducida por quimioterapia en niños / Chemotherapy-induced liver injury in children

Introducción: La lesión hepática inducida por fármacos debida a quimioterapia es una causa importante de morbilidad en enfermos oncológicos aunque sus manifestaciones clínicas son poco conocidas. Objetivo: El objetivo del presente estudio fue determinar las características (formas de presentación, gravedad y tipo de lesión) de la hepatotoxicidad por quimioterapia en niños tratados por cáncer. Pacientes y método: Se incluyó en el estudio a un total de 22 enfermos oncológico en los que, tras descartar otras causas de aumento de transaminasas (infecciosa, metabólica, autoinmune o hereditaria), se concluye, según la escala de causalidad CIOMS, que se trata de un episodio posible, probable o definido de lesión hepática por fármacos. Resultados: Todos los niños tuvieron más de un episodio de hepatotoxicidad, en total se analizan 98 episodios. Metotrexato fue el fármaco implicado con mayor frecuencia. El patrón histológico de daño predominante fue hepatocelular. Solo 2 episodios fueron clasificados de graves. Conclusiones: La hepatotoxicidad idiosincrásica por quimioterapia es frecuente, la tendencia es a la recidiva con la reexposición y, aunque no suele tener consecuencias importantes, la elevada frecuencia hace aconsejable establecer algoritmos de seguridad estandarizados con controles muy estrictos de enzimas hepáticas durante los períodos de alto riesgo de quimioterapia

Introduction: Drug-induced liver injury due to chemotherapy is an important cause of morbidity in cancer patients, although its clinical manifestations are poorly understood. Objective: The objective of the present study was to determine the characteristics (forms of presentation, severity, and type of injury) of hepatotoxicity due to chemotherapy in children treated for cancer. Patients and method: A total of 22 oncological patients were included in the study, after ruling out other causes of increased transaminases (infectious, metabolic, autoimmune, or hereditary), according to the CIOMS causality scale, it is concluded that it was a possible, probable or definite episode of hepatic injury by drugs. Results: All children had more than one episode of hepatotoxicity, and a total of 98 episodes are analysed. Methotrexate was the most commonly implicated drug. The histological pattern of predominant damage was hepatocellular. Only 2episodes were classified as serious. Conclusions: Idiosyncratic hepatotoxicity due to chemotherapy is frequent, with a tendency to relapse with re-exposure. Although it does not usually have important consequences, the high frequency makes it advisable to establish standardised safety algorithms with very strict monitoring of liver enzymes during high periods of risk in chemotherapy

[Chemotherapy-induced liver injury in children]. / Lesión hepática inducida por quimioterapia en niños.

INTRODUCTION: Drug-induced liver injury due to chemotherapy is an important cause of morbidity in cancer patients, although its clinical manifestations are poorly understood. OBJECTIVE: The objective of the present study was to determine the characteristics (forms of presentation, severity, and type of injury) of hepatotoxicity due to chemotherapy in children treated for cancer. PATIENTS AND METHOD: A total of 22 oncological patients were included in the study, after ruling out other causes of increased transaminases (infectious, metabolic, autoimmune, or hereditary), according to the CIOMS causality scale, it is concluded that it was a possible, probable or definite episode of hepatic injury by drugs. RESULTS: All children had more than one episode of hepatotoxicity, and a total of 98 episodes are analysed. Methotrexate was the most commonly implicated drug. The histological pattern of predominant damage was hepatocellular. Only 2episodes were classified as serious. CONCLUSIONS: Idiosyncratic hepatotoxicity due to chemotherapy is frequent, with a tendency to relapse with re-exposure. Although it does not usually have important consequences, the high frequency makes it advisable to establish standardised safety algorithms with very strict monitoring of liver enzymes during high periods of risk in chemotherapy.

Analysis of Immunogenetic Factors in Idiosyncratic Drug-induced Liver Injury in the Pediatric Population.

OBJECTIVES: Idiosyncratic drug-induced liver injury is a multifactorial complex disease, in which the toxic potential of the drug, together with genetic and acquired factors and deficiencies in adaptive processes, which limit the extent of damage, can determine susceptibility, and make individuals unique in their development of hepatotoxicity. The aim of the present study is to analyse the genetic factors (human leukocyte antigen [HLA], cytokine polymorphisms, and killer cell immunoglobulin-like receptor [KIR] genotype) of children who experience an episode of drug-induced liver injury. PATIENTS AND METHODS: Prospective multicentre case-control study. The subjects included in the study were 30 paediatric patients-infants and children ages between 0 and 15 years and who presented possible liver disease associated with the intake of medicines, herbal products, drugs, or toxins. As a control group, 62 subjects were selected. RESULTS: Although HLAC0401 and HLADQB0603 may provide a hepatoprotective mechanism in the paediatric population, HLADQA0102 and HLA-DR12 are more commonly found in sick children and their presence may be related to liver damage. The KIR inhibitor KIR3DL1 was not present in any child in the control group. CONCLUSIONS: Polymorphisms that are low producers of interleukin-10 occur more frequently in children who have experienced hepatotoxicity.

Una causa infrecuente de dolor abdominal en el niño / An unusual etiology of abdominal pain in children

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An unusual etiology of abdominal pain in children.

The first case of cholecystitis acalculous by Cryptosporidium in onco-hematology pediatric patient was described in this work.

[HEPATOTOXICITY FROM THE CONSUMPTION OF HERBALIST PRODUCTS BY A PAEDIATRIC POPULATION]. / HEPATOTOXICIDAD Y CONSUMO DE PRODUCTOS DE HERBORISTERÍA EN LA POBLACIÓN PEDIÁTRICA.

The consumption of herbal products is mainly due to the perception that being "natural" can only be beneficial and without risk to health. However the properties thereof are poorly studied and proven. Four episodes are presented of hepatotoxicity from the consumption of herbal products, by three children. We analyse the epidemiological and clinical characteristics of these products, and stress the importance of proper anamnesis for accurate diagnosis.

El consumo de productos de herboristería es debido principalmente a la percepción de que al ser "naturales", solo pueden ser beneficiosos y carecen de riesgos para la salud. Sin embargo, las propiedades de los mismos están escasamente estudiadas y contrastadas. Se presentan cuatro episodios de hepatotoxicidad por productos naturales en tres niños, analizándose sus características epidemiológicas y clínicas. Se hace especial hincapié en la importancia de una correcta anamnesis para la sospecha diagnóstica.

Hepatotoxicidad y consumo de productos de herboristería en la población pediátrica / Hepatotoxicity from the consumption of herbalist products by a paediatric population

El consumo de productos de herboristería es debido principalmente a la percepción de que al ser «naturales», solo pueden ser beneficiosos y carecen de riesgos para la salud. Sin embargo, las propiedades de los mismos están escasamente estudiadas y contrastadas. Se presentan cuatro episodios de hepatotoxicidad por productos naturales en tres niños, analizándose sus características epidemiológicas y clínicas. Se hace especial hincapié en la importancia de una correcta anamnesis para la sospecha diagnóstica (AU)

The consumption of herbal products is mainly due to the perception that being «natural» can only be beneficial and without risk to health. However the properties thereof are poorly studied and proven. Four episodes are presented of hepatotoxicity from the consumption of herbal products, by three children. We analyse the epidemiological and clinical characteristics of these products, and stress the importance of proper anamnesis for accurate diagnosis (AU)