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泰国一家三级护理医院肺结核患者中抗结核药物引起的肝毒性及相关危险因素

Anti-tuberculosis drug-induced hepatotoxicity and associated risk factors among patients with pulmonary tuberculosis at a tertiary care hospital in Thailand.

作者信息

Mukura Sarita, Ruenwilai Parinya

机构信息

Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

出版信息

IJID Reg. 2025 May 8;15:100665. doi: 10.1016/j.ijregi.2025.100665. eCollection 2025 Jun.

DOI:10.1016/j.ijregi.2025.100665
PMID:40547509
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12179635/
Abstract

OBJECTIVES

First-line anti-tuberculosis (TB) medications are effective for drug-susceptible TB but are commonly associated with hepatotoxicity, which can compromise treatment adherence and contribute to drug resistance. This study aimed to determine the frequency of anti-TB drug-induced hepatotoxicity and identify associated risk factors among patients at Chiang Mai University Hospital.

METHODS

A retrospective cross-sectional study was conducted among patients with drug-susceptible pulmonary TB receiving standard treatment. Liver function tests were monitored biweekly during the first 2 months to detect hepatotoxicity. The risk factors evaluated included body mass index (BMI), age, alcohol use, N-acetyltransferase 2 (NAT2) acetylator status, and concomitant statin use. Adverse drug reactions were assessed by physicians using severity grading. Binary logistic regression and multivariate analysis were performed to identify independent predictors of hepatotoxicity. Adjusted odds ratios (ORs), 95% confidence intervals (CIs), and -values were reported.

RESULTS

The incidence of hepatotoxicity was 41.97%. The multivariate analysis showed significant associations between hepatotoxicity and the following: age >70 years (OR = 41.72, = 0.001), underweight BMI (OR = 56.48, = 0.001), current alcohol use (OR = 10.95, = 0.001), and slow NAT2 acetylator status (OR = 78.18, = 0.001).

CONCLUSIONS

Hepatotoxicity is a common complication of TB treatment. Older age, low BMI, alcohol use, slow NAT2 genotype, and statin co-administration significantly increase risk. Targeted monitoring and consideration of NAT2 genotyping in high-risk patients may help prevent treatment interruptions and improve clinical outcomes.

摘要

目的

一线抗结核药物对药物敏感型结核病有效,但通常与肝毒性相关,这可能会影响治疗依从性并导致耐药性。本研究旨在确定清迈大学医院患者中抗结核药物引起的肝毒性发生率,并识别相关危险因素。

方法

对接受标准治疗的药物敏感型肺结核患者进行回顾性横断面研究。在最初2个月内每两周监测一次肝功能检查以检测肝毒性。评估的危险因素包括体重指数(BMI)、年龄、饮酒情况、N-乙酰转移酶2(NAT2)乙酰化状态以及他汀类药物的联合使用。医生使用严重程度分级评估药物不良反应。进行二元逻辑回归和多变量分析以识别肝毒性的独立预测因素。报告调整后的比值比(OR)、95%置信区间(CI)和P值。

结果

肝毒性发生率为41.97%。多变量分析显示肝毒性与以下因素之间存在显著关联:年龄>70岁(OR = 41.72,P = 0.001)、体重过低的BMI(OR = 56.48,P = 0.001)、当前饮酒(OR = 10.95,P = 0.001)以及NAT2乙酰化状态缓慢(OR = 78.18,P = 0.001)。

结论

肝毒性是结核病治疗的常见并发症。高龄、低BMI、饮酒、NAT2基因分型缓慢以及他汀类药物联合使用会显著增加风险。对高危患者进行有针对性的监测并考虑NAT2基因分型可能有助于防止治疗中断并改善临床结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0276/12179635/b3737eb5b505/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0276/12179635/2a4c51c16b1a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0276/12179635/b3737eb5b505/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0276/12179635/2a4c51c16b1a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0276/12179635/b3737eb5b505/gr2.jpg

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