Related Experiment Video

Updated: Nov 29, 2025

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

5.1K

Genetic risk factors in the development of idiosyncratic drug-induced liver injury

Camilla Stephens1, M Isabel Lucena1, Raúl J Andrade1

  • 1Unidad de Gestión Clínica de Aparato Digestivo y Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, CIBERehd, Málaga, Spain.

Expert Opinion on Drug Metabolism & Toxicology
|November 23, 2020
PubMed

Insights

Genetic factors influence drug-induced liver injury (DILI) susceptibility. While specific HLA alleles are linked to DILI, they are not useful for preemptive screening but can aid diagnosis.

Area of Science:

  • Pharmacogenomics
  • Hepatology
  • Immunogenetics

Background:

  • Idiosyncratic drug-induced liver injury (DILI) is a complex condition with unknown mechanisms.
  • Genetic factors are suspected to play a significant role in DILI susceptibility.
  • Identifying genetic risk factors for DILI has been a research priority for over 20 years.

Purpose of the Study:

  • To review genetic studies in DILI conducted to date.
  • To outline identified polymorphisms potentially involved in DILI development.
  • To discuss the clinical applications of genetic findings in DILI.

Main Methods:

  • Review of candidate gene studies in DILI.
  • Analysis of genome-wide association studies (GWAS) in DILI.
  • Evaluation of clinical applications of identified genetic associations.

Main Results:

  • Numerous polymorphisms have been associated with DILI susceptibility, though not all are consistently confirmed.
  • Genome-wide significant associations exist between specific HLA alleles and DILI caused by certain drugs.
  • These findings support the hypothesis that DILI has an immune-mediated component.

Conclusions:

  • While specific HLA alleles are linked to DILI, their low predictive value limits their use in preemptive DILI screening.
  • These genetic markers can, however, assist in DILI diagnosis and clinical decision-making.
  • Further research is needed to fully elucidate the genetic underpinnings of DILI.
Keywords:
Candidate gene studiesdrug metabolismgenome-wide association studieshuman leukocyte antigenpharmacogeneticspharmacogenomics

More Related Videos

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms11:36

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms

Published on: May 29, 2020

3.2K
Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

186

Related Concept Videos

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
90
Dosage Regimen: Individualization01:24

Dosage Regimen: Individualization

Individualization in dosing regimens is the customization of medication doses for individual patients. Its necessity arises from the goal of maximizing therapeutic benefits while minimizing risks. This approach is pivotal because human responses to drugs can vary widely; what is effective for one person may be inadequate or excessive for another. Interpatient (intersubject) variability refers to differences in drug responses between individuals, while intrapatient (intrasubject) variability...
86
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
113
Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
380
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
92
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug01:14

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
103