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儿科人群特异质性药物性肝损伤的免疫遗传因素分析

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

作者信息

Ocete-Hita Esther, Salmerón-Fernández MaJ, Urrutia-Maldonado Emilia, Muñoz-de-Rueda Paloma, Salmerón-Ruiz María, Martinez-Padilla MaC, Ruiz-Extremera Angela

机构信息

*Complejo Hospitalario Universitario de Granada, UGC Médico Quirúrgica de la Infancia, Cuidados Intensivos Pediátricos, Universidad de Granada, CIBERehd †Complejo Hospitalario Universitario de Granada, UGC Médico Quirúrgica de la Infancia ‡Laboratorios Investigación, ibs, Complejo Hospitalario Universitario de Granada, Granada §Hospital Universitario La Paz, Madrid ||Complejo Hospitalario de Jaén, Jaén ¶Complejo Hospitalario Universitario de Granada, Universidad de Granada, CIBERehd, Granada, Spain.

出版信息

J Pediatr Gastroenterol Nutr. 2017 May;64(5):742-747. doi: 10.1097/MPG.0000000000001502.

Abstract

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.

摘要

目的

特异质性药物性肝损伤是一种多因素复杂疾病,其中药物的潜在毒性,连同遗传和后天因素以及适应性过程中的缺陷(这些因素限制了损伤程度),可决定易感性,并使个体在发生肝毒性方面具有独特性。本研究的目的是分析经历药物性肝损伤发作的儿童的遗传因素(人类白细胞抗原 [HLA]、细胞因子多态性和杀伤细胞免疫球蛋白样受体 [KIR] 基因型)。

患者与方法

前瞻性多中心病例对照研究。纳入研究的对象为30例儿科患者——年龄在0至15岁之间的婴儿和儿童,他们出现了与摄入药物、草药产品、毒品或毒素相关的可能肝病。作为对照组,选择了62名受试者。

结果

虽然HLA - C0401和HLA - DQB0603可能在儿科人群中提供一种肝保护机制,但HLA - DQA0102和HLA - DR12在患病儿童中更常见,它们的存在可能与肝损伤有关。对照组中没有任何儿童存在KIR抑制剂KIR3DL1。

结论

白细胞介素 - 10低产生者的多态性在经历肝毒性的儿童中更频繁出现。

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