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

Esther Ocete-Hita1, MaJ Salmerón-Fernández, Emilia Urrutia-Maldonado

  • 1*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.

Journal of Pediatric Gastroenterology and Nutrition
|December 23, 2016
PubMed
Abstract

Insights

Genetic factors like human leukocyte antigen (HLA) and cytokine polymorphisms influence drug-induced liver injury in children. Low interleukin-10 production is linked to hepatotoxicity, highlighting genetic susceptibility in pediatric drug-induced liver injury.

Area of Science:

  • Pediatric Hepatology
  • Immunogenetics
  • Drug-Induced Liver Injury

Background:

  • Idiosyncratic drug-induced liver injury (DILI) is a complex disease influenced by drug toxicity, genetic factors, and adaptive processes.
  • Individual susceptibility to hepatotoxicity varies due to a combination of genetic and acquired factors.
  • Understanding genetic predispositions is crucial for predicting and managing DILI in children.

Purpose of the Study:

  • To investigate the role of genetic factors, including human leukocyte antigen (HLA), cytokine polymorphisms, and killer cell immunoglobulin-like receptor (KIR) genotypes, in pediatric DILI.
  • To identify specific genetic markers associated with increased susceptibility or protection against drug-induced liver injury in children.

Main Methods:

  • A prospective multicenter case-control study was conducted.
  • The study included 30 pediatric patients (0-15 years) with suspected drug-induced liver disease and 62 healthy controls.
  • Genetic analyses focused on HLA, cytokine polymorphisms (e.g., interleukin-10), and KIR genotypes.

Main Results:

  • Specific HLA alleles (HLADQA0102 and HLA-DR12) were more prevalent in children with liver injury.
  • Certain HLA alleles (HLAC0401 and HLADQB0603) may confer a hepatoprotective effect.
  • Polymorphisms associated with low interleukin-10 production were more frequent in children experiencing hepatotoxicity.

Conclusions:

  • Genetic variations, particularly in HLA and cytokine production, play a significant role in pediatric drug-induced liver injury.
  • Low interleukin-10 production is a potential risk factor for developing hepatotoxicity in children.
  • Further research into immunogenetic factors can aid in personalized risk assessment for DILI in pediatric populations.

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