Metabolomic Analysis of Pediatric Patients with Idiosyncratic Drug-Induced Liver Injury According to the Updated RUCAM.

Hepatotoxicity, a common adverse drug effect, has been extensively studied in adult patients. However, it is equally important to investigate this condition in pediatric patients to develop personalized treatment strategies for children. This study aimed to identify plasma biomarkers that characterize hepatotoxicity in pediatric patients through an observational case-control study. Metabolomic analysis was conducted on 55 pediatric patients with xenobiotic liver toxicity and 88 healthy controls. The results revealed clear differences between the two groups. Several metabolites, including hydroxydecanoylcarnitine, octanoylcarnitine, lysophosphatidylcholine, glycocholic acid, and taurocholic acid, were identified as potential biomarkers (area under the curve: 0.817; 95% confidence interval: 0.696-0.913). Pathway analysis indicated involvement of primary bile acid biosynthesis and the metabolism of taurine and hypotaurine (p < 0.05). The findings from untargeted metabolomic analysis demonstrated an increase in bile acids in children with hepatotoxicity. The accumulation of cytotoxic bile acids should be further investigated to elucidate the role of these metabolites in drug-induced liver injury.

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.

Effect of Preoperative Infusion of Levosimendan on Biomarkers of Myocardial Injury and Haemodynamics After Paediatric Cardiac Surgery: A Randomised Controlled Trial.

OBJECTIVE: The aim was to test the hypothesis that preoperative infusion of levosimendan would decrease patients' cardiac biomarker profiles during the immediate postoperative stage (troponin I and B-type natriuretic peptide levels) more efficiently than placebo after cardiopulmonary bypass. METHODS: In a randomised, placebo-controlled, double-blinded study, 30 paediatric patients were scheduled for congenital heart disease surgery. 15 patients (50%) received prophylactic levosimendan and 15 patients (50%) received placebo from 12 h before cardiopulmonary bypass to 24 h after surgery. RESULTS: Troponin I levels were higher in the placebo group at 0, 12, and 24 h after cardiopulmonary bypass, although the mean differences between the study groups and the 95% confidence intervals (CIs) for troponin I levels did not present statistically significant differences at any of the three time points considered (mean differences [95% CIs] - 3.32 pg/ml [- 19.34 to 12.70], - 2.42 pg/ml [- 19.78 to 13.95], and - 79.94 pg/ml [- 266.99 to 16.39] at 0, 12, and 24 h, respectively). A similar lack of statistically significant difference was observed for B-type natriuretic peptide (mean differences [95% CIs] 36.86 pg/dl [- 134.16 to 225.64], - 350.79 pg/dl [- 1459.67 to 557.45], and - 310.35 pg/dl [- 1505.76 to 509.82]). Lactic acid levels were significantly lower with levosimendan; the mean differences between the study groups and the 95% CIs for lactate levels present statistically significant differences at 0 h (- 1.52 mmol/l [- 3.19 to - 0.25]) and 12 h (- 1.20 mmol/l [- 2.53 to - 0.10]) after cardiopulmonary bypass. Oxygen delivery (DO2) was significantly higher at 12 h and 24 h after surgery (mean difference [95% CI] 627.70 ml/min/m2 [122.34-1162.67] and 832.35 ml/min/m2 [58.15 to 1651.38], respectively). CONCLUSIONS: Levosimendan does not significantly improve patients' postoperative troponin I and B-type natriuretic peptide profiles during the immediate postoperative stage in comparison with placebo, although both were numerically higher with placebo. Levosimendan, however, significantly reduced lactic acid levels and improved patients' DO2 profiles. These results highlight the importance of this new drug and its possible benefit with regard to myocardial injury; however, evaluation in larger, adequately powered trials is needed to determine the efficacy of levosimendan. Trial registry number: EudraCT 2012-005310-19.

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.

[Admission, discharge and triage guidelines for paediatric intensive care units in Spain]. / Guias de ingreso, alta y triage para las unidades de cuidados intensivos pediátricos en España.

A paediatric intensive care unit (PICU) is a separate physical facility or unit specifically designed for the treatment of paediatric patients who, because of the severity of illness or other life-threatening conditions, require comprehensive and continuous inten-sive care by a medical team with special skills in paediatric intensive care medicine. Timely and personal intervention in intensive care reduces mortality, reduces length of stay, and decreases cost of care. With the aim of defending the right of the child to receive the highest attainable standard of health and the facilities for the treatment of illness and rehabilitation, as well as ensuring the quality of care and the safety of critically ill paediatric patients, the Spanish Association of Paediatrics (AEP), Spanish Society of Paediatric Intensive Care (SECIP) and Spanish Society of Critical Care (SEMICYUC) have approved the guidelines for the admission, discharge and triage for Spanish PICUs. By using these guidelines, the performance of Spanish paediatric intensive care units can be optimised and paediatric patients can receive the appropriate level of care for their clinical condition.

Guías de ingreso, alta y triage para las unidades de cuidados intensivos pediátricos en España / Admission, discharge and triage guidelines for paediatric intensive care units in Spain

La unidad de cuidados intensivos pediátricos (UCIP) es una unidad física asistencial hospitalaria independiente especialmente diseñada para el tratamiento de pacientes pediátricos quienes debido su gravedad o condiciones potencialmente letales requieren observación y asistencia médica intensiva integral y continua por un equipo médico que haya obtenido competencia especial en medicina intensiva pediátrica. La aplicación oportuna de terapia intensiva a los pacientes críticos reduce la mortalidad, el tiempo de estancia y los costes asistenciales. Con los objetivos de respetar el derecho del niño al disfrute del más alto nivel posible de salud y a servicios para el tratamiento de las enfermedades y la rehabilitación de la salud y de garantizar la calidad asistencial y la seguridad de los pacientes pediátricos críticos, la Asociación Española de Pediatría (AEP), la Sociedad Española de Cuidados Intensivos Pediátricos (SECIP) y la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) han desarrollado y aprobado las guías de ingreso, alta y triage para las UCIP en España. Mediante la aplicación de estas guías se puede optimizar el uso de las UCIP españolas de forma que los pacientes pediátricos reciban el nivel de cuidados médicos más apropiado para su situación clínica

A paediatric intensive care unit (PICU) is a separate physical facility or unit specifically designed for the treatment of paediatric patients who, because of the severity of illness or other life-threatening conditions, require comprehensive and continuous intensive care by a medical team with special skills in paediatric intensive care medicine. Timely and personal intervention in intensive care reduces mortality, reduces length of stay, and decreases cost of care. With the aim of defending the right of the child to receive the highest attainable standard of health and the facilities for the treatment of illness and rehabilitation, as well as ensuring the quality of care and the safety of critically ill paediatric patients, the Spanish Association of Paediatrics (AEP), Spanish Society of Paediatric Intensive Care (SECIP) and Spanish Society of Critical Care (SEMICYUC) have approved the guidelines for the admission, discharge and triage for Spanish PICUs. By using these guidelines, the performance of Spanish paediatric intensive care units can be optimised and paediatric patients can receive the appropriate level of care for their clinical condition

Guias de ingreso, alta y triage para las unidades de cuidados intensivos pediátricos en España / Admission, discharge and triage guidelines for paediatric intensive care units in Spain

La unidad de cuidados intensivos pediátricos (UCIP) es una unidad física asistencial hospitalaria independiente especialmente diseñada para el tratamiento de pacientes pediátricos quienes debido su gravedad o condiciones potencialmente letales requieren observación y asistencia médica intensiva integral y continua por un equipo médico que haya obtenido competencia especial en medicina intensiva pediátrica. La aplicación oportuna de terapia intensiva a los pacientes críticos reduce la mortalidad, el tiempo de estancia y los costes asistenciales. Con los objetivos de respetar el derecho del niño al disfrute del más alto nivel posible de salud y a servicios para el tratamiento de las enfermedades y la rehabilitación de la salud y de garantizar la calidad asistencial y la seguridad de los pacientes pediátricos críticos, la Asociación Española de Pediatría (AEP), la Sociedad Española de Cuidados Intensivos Pediátricos (SECIP) y la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) han desarrollado y aprobado las guías de ingreso, alta y triage para las UCIP en España. Mediante la aplicación de estas guías se puede optimizar el uso de las UCIP españolas de forma que los pacientes pediátricos reciban el nivel de cuidados médicos más apropiado para su situación clínica

A paediatric intensive care unit (PICU) is a separate physical facility or unit specifically designed for the treatment of paediatric patients who, because of the severity of illness or other life-threatening conditions, require comprehensive and continuous inten-sive care by a medical team with special skills in paediatric intensive care medicine. Timely and personal intervention in intensive care reduces mortality, reduces length of stay, and decreases cost of care. With the aim of defending the right of the child to receive the highest attainable standard of health and the facilities for the treatment of illness and rehabilitation, as well as ensuring the quality of care and the safety of critically ill paediatric patients, the Spanish Association of Paediatrics (AEP), Spanish Society of Paediatric Intensive Care (SECIP) and Spanish Society of Critical Care (SEMICYUC) have approved the guidelines for the admission, discharge and triage for Spanish PICUs. By using these guidelines, the performance of Spanish paediatric intensive care units can be optimised and paediatric patients can receive the appropriate level of care for their clinical condition

Admission, discharge and triage guidelines for paediatric intensive care units in Spain. / Guias de ingreso, alta y triage para las unidades de cuidados intensivos pediátricos en España.

A paediatric intensive care unit (PICU) is a separate physical facility or unit specifically designed for the treatment of paediatric patients who, because of the severity of illness or other life-threatening conditions, require comprehensive and continuous inten-sive care by a medical team with special skills in paediatric intensive care medicine. Timely and personal intervention in intensive care reduces mortality, reduces length of stay, and decreases cost of care. With the aim of defending the right of the child to receive the highest attainable standard of health and the facilities for the treatment of illness and rehabilitation, as well as ensuring the quality of care and the safety of critically ill paediatric patients, the Spanish Association of Paediatrics (AEP), Spanish Society of Paediatric Intensive Care (SECIP) and Spanish Society of Critical Care (SEMICYUC) have approved the guidelines for the admission, discharge and triage for Spanish PICUs. By using these guidelines, the performance of Spanish paediatric intensive care units can be optimised and paediatric patients can receive the appropriate level of care for their clinical condition.

Distracción mandibular ósea: resultados del postoperatorio inmediato / Mandibular distraction osteogenesis: immediate postoperative outcome

Introducción. La distracción osteogénica mandibular es una relativamente nueva técnica quirúrgica de alargamiento mandibular para aliviar la obstrucción de la vía aérea en pacientes con hipoplasia mandibular. Ha revolucionado el manejo de defectos en el campo de la cirugía craneofacial, y el procedimiento se ha convertido en ampliamente aceptado en hospitales de todo el mundo. Objetivos. Describir la evolución y la tasa de complicaciones en el postoperatorio inmediato de la distracción osteogénica mandibular en el Hospital Materno-Infantil de Granada, hospital de referencia andaluz de dicha técnica. Material y métodos. Estudio observacional descriptivo de los niños en los que se ha realizado una distracción mandibular en el período comprendido entre los años 2006 y 2016. Se incluyen un total de 20 pacientes. Los datos han sido analizados con el paquete estadístico IBM SPSS Statistics 20. Resultados. Precisaron ingreso en la UCIP durante 5,5 días de mediana (2-9), los días totales de ingreso hospitalario fueron de 8 días de mediana (4,25-14). Un total de 10 enfermos (50%) presentaron fiebre. Se consiguió instaurar la nutrición enteral, de media, a los 2 días de la intervención. Conclusiones. Los pacientes con secuencia Pierre Robin pueden presentar retro/micrognatia grave que les produzca desde dificultad a la entrada de aire hasta apnea obstructiva, en cuyo caso la distracción mandibular es el tratamiento de elección. El postoperatorio de dicha intervención requiere estancia en UCIP para el manejo de la vía aérea, entre otros. Según los datos que presentamos, concluimos que el postoperatorio es corto y con una baja tasa de complicaciones (AU)

Introduction. Mandibular distraction osteogenesis is a relatively new surgical technique to relieve mandibular lengthening airway obstruction in patients with mandibular hypoplasia. It has revolutionised the management of defects in the field of craniofacial surgery, and the procedure has become widely accepted in hospitals worldwide. Goals. To describe the evolution and rate of complications in the immediate postoperative period following mandibular distraction osteogenesis in the Mother and Child Hospital of Granada, Andalusia's referral hospital for this technique. Material and methods. Descriptive observational study of children who underwent mandibular distraction in the period between 2006 and 2016. A total of 20 patients were included. The data were analysed with the statistical package SPSS Statistics 20. Results. The children required admission to ICU for a median of 5.5 days (2-9), the total days of hospital stay were a median of 8 (4.25 to 14). A total of 10 patients (50%) developed a fever. Enteral nutrition was established, on average, at 2 days after surgery. Conclusions. Patients with Pierre Robin sequence may have severe retro/micrognathia causing them symptoms including from difficulty in air entry to obstructive apnoea, in which case mandibular distraction is the treatment of choice. After this intervention the postoperative period should be in ICU for airway management and other care. According to the data presented, we conclude that the postoperative period is short and with a low rate of complications (AU)

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.

[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)

Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001) and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05) than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV-infected children.

UNLABELLED: The vertical transmission of hepatitis C virus (HCV-VT) is a major route of HCV infection in children, but the risk factors remain incompletely understood. This study analyzed the role of interleukin 28B (IL28B) in HCV-VT and in the spontaneous clearance of HCV among infected infants. Between 1991 and 2009, 145 mothers were recruited for this study: 100 were HCV-RNA+ve / human immunodeficiency virus negative (HIV-ve), with 128 children, and 33 were HCV-RNA-ve/HCV antibody+ve, with 43 children. The infants were tested for HCV-RNA at birth and at regular intervals until the age of 6 years. IL28B (single nucleotide polymorphism rs12979860) was determined in the mothers and children. HCV-VT was assumed when children presented HCV-RNA+ve in two subsequent blood samples. HCV-VT-infected infants were categorized as: (1) transient viremia with posterior HCV-RNA-ve and without serum-conversion; (2) persistent infection with serum-conversion. Of the 31 mothers with CC polymorphism, 19 (61%) were HCV-RNA+ve, whereas among the 68 mothers with non-CC polymorphism, 56 (82%) were HCV-RNA+ve. In all, 26 of 128 (20%) infants born to the HCV-RNA+ve mothers acquired HCV infection, but only 9 (7%) were chronically infected. The rate of HCV-VT was higher among the mothers with higher HCV viremia. No HCV-VT was detected in the HCV-RNA-ve women. Neither the mothers' nor the childrens' IL-28 status was associated with an increased risk of HCV-VT. The factors influencing viral clearance among the infected children were genotype non-1 and genotype CC of IL28B. In logistic regression, child CC polymorphism was the only predictor of HCV-clearance in HCV genotype-1. CONCLUSION: High maternal viral load is the only predictive factor of HCV-VT. IL28B plays no role in HCV-VT, but IL28B CC child polymorphism is associated independently with the spontaneous clearance of HCV genotype-1 among infected children.

Activity of hepatic enzymes from week sixteen of pregnancy.

OBJECTIVE: This study was undertaken to determine the prevalence, epidemiology, and mother-child repercussions of increased alanine-aminotransferase levels from week 16 of pregnancy. STUDY DESIGN: A longitudinal observational study of 381 pregnant women. The cause of increased alanine-aminotransferase levels during pregnancy and repercussions on the neonate were studied in 283 cases. Statistical analysis was performed with Mann-Whitney test, chi2 test, or the Fisher exact test. RESULTS: The mean age of the mothers was 29.9 +/- 4.8 years. Twenty-five percent presented increased gamma-glutamyl-transpeptidase, alkaline phophatase, and dehydrogenase lactate from week 32. Increased alanine-aminotransferase was observed in 7.4% (95% CI, 5.00%-10.57%) of cases. Clinical disorders were light, transitory, and with no apparent cause, except for 1 hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, 3 preeclampsias, and 1 gravidic cholestasis. No statistically significant differences were observed in the group of mother-child with alanine-aminotransferase normal or increased. CONCLUSION: Most increases in alanine-aminotransferase from week 16 of pregnancy are transitory, non-specific, and have no repercussions on mother or child.