Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
Sci Rep. 2020 Apr 15;10(1):6462. doi: 10.1038/s41598-020-63156-8.
Poor adherence to medication can lead to treatment failure in healthcare workers (HWCs) with latent tuberculosis infection (LTBI) who are at high risk of developing active tuberculosis. However, the factors associated with non-completion of nine-month LTBI treatment with isoniazid (9 H) have not been well studied. We investigated the completion rate and factors affecting adherence to LTBI treatment with 9 H among HCWs. A prospective cohort study of 114 HCWs who were diagnosed with LTBI by QuantiFERON-TB Gold In-Tube tests were performed in a single university hospital between June 2016 and December 2017. All patients received the 9 H LTBI treatment. At each visit, treatment adherence and development of adverse reactions to isoniazid were evaluated via a standard questionnaire. To evaluate the impact of the severity of hepatotoxicity on non-completion of LTBI treatment, we classified hepatotoxicity into two groups: severe hepatotoxicity was defined as alanine aminotransferase >3.0 times the upper normal limit (UNL) with symptoms or = 5.0 times the UNL. Mild hepatotoxicity was defined as alanine aminotransferase>UNL, but not meet the definition of severe hepatotoxicity. Overall, 71 HCWs (62.3%) completed LTBI treatment with 9 H while 43 HCWs (37.7%) discontinued their treatment. Most discontinuation (81.4%, 35/43) occurred during the first three months of treatment. There were no significant differences in age, sex, occupation, or comorbidities between the HCWs who completed and those who discontinued LTBI treatment. However, HCWs who discontinued LTBI treatment had more hepatotoxicity than those who completed treatment (44.2% vs. 11.3%, P < 0.001). Cox proportional hazard analysis revealed that hepatotoxicity is the only factor significantly associated with discontinuation of 9 H LTBI treatment (unadjusted HR = 2.89, 95% CI = 1.62-5.46). In multivariable analysis, not only severe hepatotoxicity (adjusted HR = 7.99, 95% CI = 3.05-20.94) but also mild hepatotoxicity was significantly associated with discontinuation of LTBI treatment (adjusted HR = 2.34, 95% CI = 1.05-5.21). The completion rate of 9 H LTBI treatment was 62.3% among HCWs. While age, sex, occupation, and pretreatment comorbidities were not associated with treatment completion, isoniazid-induced hepatotoxicity significantly affected adherence.
依从性差可导致潜伏性结核感染（LTBI）的医护人员（HCWs）治疗失败，这些人有发展为活动性结核病的高风险。然而，尚未很好地研究导致使用异烟肼（INH）完成 9 个月 LTBI 治疗的相关因素。我们调查了使用 INH 进行 9 个月 LTBI 治疗的 HCWs 完成率和影响依从性的因素。2016 年 6 月至 2017 年 12 月，在一家大学医院对通过 QuantiFERON-TB Gold In-Tube 检测诊断为 LTBI 的 114 名 HCWs 进行了前瞻性队列研究。所有患者均接受 9 个月 INH LTBI 治疗。每次就诊时，通过标准问卷评估治疗依从性和 INH 引起的不良反应的发展情况。为了评估肝毒性严重程度对 LTBI 治疗不完成的影响，我们将肝毒性分为两组：严重肝毒性定义为丙氨酸氨基转移酶（ALT）>3.0 倍正常值上限（ULN）并伴有症状或≥5.0 倍 ULN；轻度肝毒性定义为 ALT>ULN，但不符合严重肝毒性的定义。总体而言，71 名 HCWs（62.3%）完成了 9 个月 INH LTBI 治疗，43 名 HCWs（37.7%）停止了治疗。大多数停药（81.4%，35/43）发生在治疗的前三个月。完成和未完成 LTBI 治疗的 HCWs 在年龄、性别、职业或合并症方面无显著差异。然而，停止 LTBI 治疗的 HCWs的肝毒性发生率高于完成治疗的 HCWs（44.2% vs. 11.3%，P<0.001）。Cox 比例风险分析显示，肝毒性是唯一与 9 个月 INH LTBI 治疗停药显著相关的因素（未调整 HR=2.89，95%CI=1.62-5.46）。多变量分析显示，不仅严重肝毒性（调整 HR=7.99，95%CI=3.05-20.94），而且轻度肝毒性也与 LTBI 治疗停药显著相关（调整 HR=2.34，95%CI=1.05-5.21）。HCWs 中 9 个月 INH LTBI 治疗的完成率为 62.3%。虽然年龄、性别、职业和治疗前合并症与治疗完成无关，但异烟肼引起的肝毒性显著影响了依从性。
