Retrospective Henan tuberculosis cohort finds no significant link between slow NAT2 acetylation and new liver abnormalities

A retrospective, single-center study of patients with tuberculosis found that genotype-inferred slow N-acetyltransferase 2 (NAT2) acetylator status was not significantly associated with new in-hospital liver function abnormality. In the primary analysis, 143 of 554 eligible patients developed the outcome, including 29 of 101 slow acetylators and 114 of 453 non-slow acetylators. The adjusted association was not statistically significant, although the analysis could not exclude smaller or moderate effects.

The study included 801 patients who underwent NAT2 genotyping at Henan Provincial Chest Hospital between January 2021 and May 2024. The full cohort was used to characterize the distribution of slow, intermediate and fast acetylator status. The primary analysis was restricted to 554 patients who had normal liver function at admission and a recorded isoniazid dose, while a secondary cohort comprised 690 patients with normal baseline liver function. The principal comparison was slow acetylator status with non-slow status, including intermediate and fast acetylators combined.

Across the 801 participants, 369 (46.1%) were intermediate acetylators, 278 (34.7%) were fast acetylators and 154 (19.2%) were slow acetylators. New liver function abnormalities occurred in 28.7% (29/101) of slow acetylators and 25.2% (114/453) of non-slow acetylators in the primary cohort, yielding a crude odds ratio of 1.20 (95% confidence interval [CI], 0.73–1.92; P = 0.462). Adjustment for age, sex and recorded isoniazid dose produced a similar estimate: adjusted OR, 1.18 (95% CI, 0.72–1.89; P = 0.507). An additional analysis adjusting for pulmonary tuberculosis and isoniazid susceptibility gave an OR of 1.18 (95% CI, 0.72–1.90; P = 0.505). Secondary and sensitivity analyses were reported as consistent with the primary result.

The findings remain limited by the study’s retrospective, single-center design and the statistical uncertainty surrounding the estimated association. At 80% power, the approximate minimum detectable odds ratio for a risk-increasing association was 1.94, meaning the available analysis was not sufficiently precise to rule out smaller effects. The outcome was not causally adjudicated as antituberculosis-drug-induced liver injury, and systematic pharmacokinetic and longitudinal treatment data were unavailable. The abstract therefore concludes that the results do not establish the clinical utility of NAT2-guided dosing. Prospective multicenter validation is needed, and the findings should not be interpreted as evidence that genotype-guided dosing lacks clinical value.

Subject of Research: NAT2 genotype-inferred acetylator status and new liver function abnormalities in patients with tuberculosis

Article Title: The distribution of N-acetyltransferase 2 genotypes in a cohort of tuberculosis patients in a single center in Henan Province of China

Article References: Li, J., Chen, L., Shi, H., Zhao, C., Xu, P., Mo, Y., Liu, X., Zhao, Y., & Liang, R. (2026). The distribution of N-acetyltransferase 2 genotypes in a cohort of tuberculosis patients in a single center in Henan Province of China. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14424-x

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14424-x

Keywords: NAT2, tuberculosis, acetylator status, liver function, isoniazid, retrospective cohort, Henan Province, pharmacogenetics, distribution, N-acetyltransferase, genotypes, cohort