Epigenetic insights into anti-tuberculosis drug-induced liver injury: A systematic review of DNA methylation as a potential biomarker.

In 30 seconds

This systematic review assessed whether DNA methylation patterns are associated with susceptibility to anti-tuberculosis drug-induced liver injury (ATDILI). Searches identified eight eligible case-control studies published between 2014 and 2024. The studies reported ATDILI associations with hypermethylation in several drug-metabolism and other genes, as well as hypomethylation of repetitive elements; genome-wide analyses also suggested additional candidate markers. The review supports DNA methylation as a potential biomarker of ATDILI susceptibility, but the evidence does not establish causality, timing, or clinical predictive value.

Key findings

• Eight case-control studies published between 2014 and 2024 met the review’s eligibility criteria.
• ATDILI-associated hypermethylation was reported in NAT2, CYP2E1, CYP2D6, CYP1A1, GSTP1, HIF1α, and ALAS1.
• Global hypomethylation of LINE-1, SINE, and ALU repetitive elements was associated with increased ATDILI risk.
• Genome-wide analyses identified candidate markers in TANC1, SLC8A2, PSTPIP2, and AK2.

Why it matters

A biomarker that identifies susceptibility to ATDILI could eventually inform individualized risk assessment during tuberculosis treatment. This review brings together reported methylation associations across candidate genes and genome-wide analyses, while highlighting that these signals remain preliminary. Establishing whether they predict injury reliably and add useful information to clinical assessment is necessary before they can guide care.

What to keep in mind

All included evidence came from case-control studies, so causal and temporal relationships are uncertain. The review calls for prospective longitudinal studies, mechanistic validation, and large-scale replication to establish predictive and clinical utility.