Research Progress of Pharmacogenomics in Drug-Induced Liver Injury.

Qihui Shao,Zhixuan Zhou,Xinyu Mao,Zhiling Li,Cong Huai

doi:10.3389/fphar.2021.735260

Abstract

Background: Drug-induced liver injury (DILI) is a common and serious adverse drug reaction with insufficient clinical diagnostic strategies and treatment methods. The only clinically well-received method is the Roussel UCLAF Causality Assessment Method scale, which can be applied to both individuals and prospective or retrospective studies. However, in severe cases, patients with DILI still would develop acute liver failure or even death. Pharmacogenomics, a powerful tool to achieve precision medicine, has been used to study the polymorphism of DILI related genes.Summary: We summarized the pathogenesis of DILI and findings on associated genes and variations with DILI, including but not limited to HLA genes, drug metabolizing enzymes, and transporters genes, and pointed out further fields for DILI related pharmacogenomics study to provide references for DILI clinical diagnosis and treatment.Key Messages: At present, most of the studies are mainly limited to CGS and GWAS, and there is still a long way to achieve clinical transformation. DNA methylation could be a new consideration, and ethnic differences and special populations also deserve attention.

Highlights

Drug induced liver injury (DILI) refers to the liver injury induced by all kinds of prescription or nonprescription chemical drugs, biological agents, traditional Chinese medicine, natural medicine, health care products, dietary supplements and their metabolites or even excipients (Yu et al, 2017)
Rs199650082 of nucleus signaling-1 (ERN1) is significantly related to DILI, while in antiretroviral therapy combined with anti-tuberculosis therapy, transcriptional variation of synaptotagmin 1 (Syt1) rs4842407 is associated with DILI (Petros et al, 2017)
Due to the complexity of the mechanisms of DILI, here we introduce a relatively accepted explanation, while the pathogenesis is still inconclusive and needs further research

Summary

Introduction

Drug induced liver injury (DILI) refers to the liver injury induced by all kinds of prescription or nonprescription chemical drugs, biological agents, traditional Chinese medicine, natural medicine, health care products, dietary supplements and their metabolites or even excipients (Yu et al, 2017). Drug induced liver injuries are classified into dose-dependent type and dose-independent type, or named intrinsic type and idiosyncratic type, respectively. The onset of intrinsic DILI is caused by the direct toxicity of drugs or their metabolites, so it is predictable and the incubation period is short (several hours to several days); the onset of idiosyncratic DILI is often unpredictable and the incubation period is uncertain (Katarey and Verma, 2016; European Association for the Study of the Liver, 2019), which cannot be predicted or simulated by animal models. Drug-induced liver injury (DILI) is a common and serious adverse drug reaction with insufficient clinical diagnostic strategies and treatment methods. In severe cases, patients with DILI still would develop acute liver failure or even death. Pharmacogenomics, a powerful tool to achieve precision medicine, has been used to study the polymorphism of DILI related genes

Methods

Findings

Discussion

Conclusion