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CYP2E1 and CYP2D6 in Anti-Tuberculosis Drug-Induced Liver Injury: Mechanisms, Epigenetic Regulation, and

Pathida Prakongsup1, Wanvisa Udomsinprasert2,3

  • 1Master of Science Program in Biopharmaceutical Sciences, Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

Clinical and Translational Science
|June 8, 2026
PubMed

Insights

Epigenetic changes, specifically DNA methylation of CYP enzymes, are key to understanding anti-tuberculosis drug-induced liver injury (ATDILI). This research explores these pharmacoepigenetic mechanisms for better TB treatment safety.

Area of Science:

  • Pharmacology
  • Hepatology
  • Epigenetics

Background:

  • Tuberculosis (TB) remains a global health challenge.
  • Anti-tuberculosis drug-induced liver injury (ATDILI) is a major adverse effect of TB treatment.
  • The precise mechanisms of ATDILI are not fully understood, but epigenetic factors are increasingly implicated.

Purpose of the Study:

  • To review the current understanding of pharmacoepigenetic mechanisms in ATDILI.
  • To focus on the role of DNA methylation in cytochrome P450 (CYP) enzymes, specifically CYP2E1 and CYP2D6.
  • To explore the potential of DNA methylation as biomarkers and therapeutic targets for ATDILI.

Main Methods:

  • Literature review synthesizing current research on ATDILI and epigenetics.
  • Focus on studies investigating DNA methylation patterns of CYP2E1 and CYP2D6.
  • Analysis of evidence linking epigenetic modifications to drug metabolism and hepatotoxicity.

Main Results:

  • Aberrant DNA methylation of CYP2E1 may affect isoniazid metabolism, leading to liver injury.
  • CYP2D6 methylation might contribute to ATDILI through impaired detoxification and autoimmune responses, especially in coinfected patients.
  • DNA methylation signatures show potential as diagnostic biomarkers and targets for epigenome editing.

Conclusions:

  • Epigenetic dysregulation, particularly CYP enzyme DNA methylation, plays a significant role in ATDILI.
  • Further research integrating multi-omics and AI is needed for early prediction and personalized management of ATDILI.
  • Understanding these epigenetic factors is crucial for developing safer TB therapies and aiding TB eradication efforts.
Keywords:
CYP2D6DNA methylationanti‐tuberculosis drug‐induced liver injury (ATDILI)cytochrome P450 CYP2E1epigenome editingpharmacoepigenetics

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