An Immunological Perspective on the Mechanism of Drug Induced Liver Injury: Focused on Drugs for Treatment of Hepatocellular Carcinoma and Liver Transplantation

Int J Mol Sci. 2023 Mar 5;24(5):5002. doi: 10.3390/ijms24055002.

Abstract

The liver is frequently exposed to potentially toxic materials, and it is the primary site of clearance of foreign agents, along with many innate and adaptive immune cells. Subsequently, drug induced liver injury (DILI), which is caused by medications, herbs, and dietary supplements, often occurs and has become an important issue in liver diseases. Reactive metabolites or drug-protein complexes induce DILI via the activation of various innate and adaptive immune cells. There has been a revolutionary development of treatment drugs for hepatocellular carcinoma (HCC) and liver transplantation (LT), including immune checkpoint inhibitors (ICIs), that show high efficacy in patients with advanced HCC. Along with the high efficacy of novel drugs, DILI has become a pivotal issue in the use of new drugs, including ICIs. This review demonstrates the immunological mechanism of DILI, including the innate and adaptive immune systems. Moreover, it aims to provide drug treatment targets, describe the mechanisms of DILI, and detail the management of DILI caused by drugs for HCC and LT.

Keywords: B cell; T cell; hepatocellular carcinoma; hepatotoxicity; immune checkpoint inhibitors; immunosuppressant; injury; macrophage; microenvironment; tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Carcinoma, Hepatocellular*
  • Chemical and Drug Induced Liver Injury*
  • Humans
  • Liver Neoplasms*
  • Liver Transplantation*