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.

Síndrome de fatiga crónica en adolescentes / Chronic fatigue syndrome in adolescents

No disponible

[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.