PDF(Pubmed)
Abstract：
Background: Screening and treating healthcare workers (HCWs) for latent tuberculosis infection (LTBI) are essential for tuberculosis (TB) infection control. Adverse drug reactions (ADRs) to anti-TB drugs present challenges to patient safety and treatment completion. Objective: This study investigated the association between human leukocyte antigen (HLA) alleles and the risk of ADRs, especially drug hypersensitivity (DHS) and hepatotoxicity, in HCWs with LTBI receiving isoniazid (INH) and rifampin (RIF) therapy. Methods: Korean HCWs with LTBI who received a 3 month INH and RIF regimen were included in this study. HLA genotyping was performed on HCWs who experienced ADRs during treatment, as well as the control group consisted of individuals who did not develop ADRs. Results: Of the 67 patients, 29 (43.2%) experienced ADRs during INH and RIF therapy. The HLA-A*11:01 allele was more frequent in patients with DHS without hepatotoxicity (DSH+/H-) compared to the control group (DHS-/H-) (4/9, 44.4% vs. 3/38, 7.9%; odd ratio [OR], 8.554; 95% confidence interval [CI], 1.415-59.869; p = 0.018). Conversely, HLA-DPB1*05:01 was associated with an increased risk of hepatotoxicity regardless of DHS (10/20, 50% vs. 5/38, 13.2%; OR, 5.323; 95% CI, 1.493-21.518; p = 0.011). In the DHS with hepatotoxicity group (DHS+/H+), HLA-DPB1*05:01 was present in a higher proportion (3/5, 60% vs. 5/38, 13.2%; OR, 8.912; 95% CI, 1.110-92.993; p = 0.037), whereas HLA-A*11:01 was not observed in this group. Conclusions: The HLA-A*11:01 allele was associated with an increased risk of DHS without hepatotoxicity, whereas the HLA-DPB1*05:01 allele was associated with an increased risk of hepatotoxicity.
摘要：
背景：筛查和治疗潜在结核病感染（LTBI）的医护人员（HCWs）对于控制结核病（TB）感染至关重要。抗结核药物的不良反应（ADR）对患者安全和治疗完成提出了挑战。目的：本研究探讨人类白细胞抗原（HLA）等位基因与ADR风险之间的关系。尤其是药物超敏反应（DHS）和肝毒性，在接受异烟肼（INH）和利福平（RIF）治疗的LTBIHCWs中。方法：本研究包括接受3个月INH和RIF方案的患有LTBI的韩国HCWs。对治疗期间出现ADR的HCWs进行HLA基因分型，以及对照组由未发生ADR的个体组成.结果：在67例患者中，29例（43.2%）在INH和RIF治疗期间出现不良反应。与对照组（DHS-/H-）相比，无肝毒性的DHS患者（DSH/H-）的HLA-A*11：01等位基因频率更高（4/9，44.4％vs.3/38，7.9%；奇数比率[OR]，8.554；95%置信区间[CI]，1.415-59.869；p=0.018）。相反，HLA-DPB1*05:01与肝毒性风险增加相关，无论DHS如何（10/20，50％vs.5/38，13.2%；或，5.323；95%CI，1.493-21.518；p=0.011）。在具有肝毒性的DHS组（DHS/H）中，HLA-DPB1*05:01的比例较高（3/5，60%vs.5/38，13.2%；或，8.912；95%CI，1.110-92.993；p=0.037），而在该组中未观察到HLA-A*11:01。结论：HLA-A*11:01等位基因与DHS风险增加相关，无肝脏毒性，而HLA-DPB1*05:01等位基因与肝毒性风险增加相关.
