Risk Factors for Idiosyncratic Drug-Induced Liver Injury

Naga Chalasani, Einar Björnsson

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

Idiosyncratic drug-induced liver injury (DILI) is a rare disorder that is not related directly to dosage and little is known about individuals who are at increased risk. There are no suitable preclinical models for the study of idiosyncratic DILI and its pathogenesis is poorly understood. It is likely to arise from complex interactions among genetic, nongenetic host susceptibility, and environmental factors. Nongenetic risk factors include age, sex, and other diseases (eg, chronic liver disease or human immunodeficiency virus infection). Compound-specific risk factors include daily dose, metabolism characteristics, and propensity for drug interactions. Alcohol consumption has been proposed as a risk factor for DILI from medications, but there is insufficient evidence to support this. Many studies have explored genetic defects that might be involved in pathogenesis and focused on genes involved in drug metabolism and the immune response. Multicenter databases of patients with DILI (the United States Drug Induced Liver Injury Network, DILIGEN, and the Spanish DILI registry) are important tools for clinical and genetic research. A genome-wide association study of flucloxacillin hepatotoxicity has yielded groundbreaking results and many similar studies are underway. Nonetheless, DILI is challenging to investigate because of its rarity, the lack of experimental models, the number of medications that might cause it, and challenges to diagnosis.

Original languageEnglish
Pages (from-to)2246-2259
Number of pages14
JournalGastroenterology
Volume138
Issue number7
DOIs
StatePublished - Jun 2010

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Chemical and Drug Induced Liver Injury
Floxacillin
Genetic Research
Genome-Wide Association Study
Virus Diseases
Drug Interactions
Alcohol Drinking
Registries
Liver Diseases
Chronic Disease
Theoretical Models
HIV
Databases
Pharmaceutical Preparations

Keywords

  • Amoxicillin-Clavulanate
  • DILI
  • HLA
  • Hy's Law

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Risk Factors for Idiosyncratic Drug-Induced Liver Injury. / Chalasani, Naga; Björnsson, Einar.

In: Gastroenterology, Vol. 138, No. 7, 06.2010, p. 2246-2259.

Research output: Contribution to journalArticle

Chalasani, Naga ; Björnsson, Einar. / Risk Factors for Idiosyncratic Drug-Induced Liver Injury. In: Gastroenterology. 2010 ; Vol. 138, No. 7. pp. 2246-2259.
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