Anti-tuberculosis (TB) drugs like isoniazid and rifampin can cause hepatotoxicity leading to treatment termination. Although Genome-wide association studies (GWAS) have identified variants linked to the risk of developing anti-tuberculosis drug-induced liver injury (AT-DILI), findings remain inconsistent. This study aimed to systematically summarise previous observational studies and assess the association between genetic polymorphisms and AT-DILI risk in adults. We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Libraries until January 10, 2023. The Newcastle-Ottawa Scale checklist was used to assess the methodological quality of the included studies. Pooled odds ratios (OR) with 95% confidence intervals (CIs) were employed using a random-effect model with the I2 statistic to estimate the heterogeneity of results. Our study included 10 studies (n=3,322) of Asian ancestry. We identified genetic variants in drug-metabolizing enzymes, including NAT2, CYP2E1, and PXR, linked to AT-DILI risk. CYP2E1 C1/C1 and slow acetylators of NAT2*6A/6A, NAT26A/7B, NAT27B/7B, and NAT25B/7B genotypes were associated with increased risk, while rapid acetylators of NAT24/4 and NAT24/7B were linked to decreased risk. No significant association was found between CYP2E1B C1/C2, NAT2(*4/*6A, *4/*5B, *5B/*5B) and PXR with AT-DILI risk. This study revealed that NAT2 slow acetylator genotypes or CYP2E1 C1/C1 are causally linked to AT-DILI risk. The findings suggest that genetic variants in drug-metabolizing enzymes regulated by NAT2 and CYP2E1 are involved in developing drug-induced liver injury in users of anti-TB drugs.

The authors have declared no competing interest.

This study did not receive any funding

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All data produced in the present study are available upon reasonable request to the authors