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ABO 血型与抗结核药物性肝损伤的关联:来自中国汉族人群的病例对照研究。

Association of ABO blood group and antituberculosis drug-induced liver injury: A case-control study from a Chinese Han population.

机构信息

Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.

Department of Infectious Disease, The Jurong Hospital Affiliated to Jiangsu University, Jurong, China.

出版信息

J Clin Pharm Ther. 2020 Aug;45(4):638-645. doi: 10.1111/jcpt.13139. Epub 2020 Apr 7.

Abstract

WHAT IS KNOWN AND OBJECTIVE

Antituberculosis drug-induced liver injury (ATLI) is a serious adverse drug reaction, and its pathogenic mechanism is still largely unknown. Rifampin (RIF) has been reported to cause haemolysis due to the production of drug-dependent antibodies, and haemolysis results in an increased level of free haem, which affects the function of hepatocytes. Blood group determinants can act as specific receptor sites for drug-antibody complexes, causing erythrocyte destruction in the presence of RIF. RIF-induced immune haemolysis may be a potential mechanism for ATLI. Thus, the study aimed to explore the role of ABO blood group systems in Chinese ATLI patients.

METHODS

A 1:4 matched case-control study was conducted among 146 ATLI cases and 584 controls. Multivariable conditional logistic regression and Cox proportional regression were used to estimate the association between ABO blood group and risk of ATLI by odds ratio (OR), hazards ratio (HR) and 95% confidence intervals (CIs), and liver disease history and taking hepatoprotectant were used as covariates.

RESULTS AND DISCUSSION

Patients in the A, B, AB and non-O blood groups had a significantly higher risk of ATLI than those in the O blood group (OR = 1.832, 95% CI: 1.126-2.983, P = .015; OR = 1.751, 95% CI: 1.044-2.937, P = .034; OR = 2.059, 95% CI: 1.077-3.938, P = .029; OR = 1.822, 95% CI: 1.173-2.831, P = .007, respectively). After considering the time of ALTI occurrence, similar results were found in the A, B, AB and non-O blood groups (HR = 1.676, 95% CI: 1.072-2.620, P = .024; HR = 1.620, 95% CI: 1.016-2.584, P = .043; HR = 2.010, 95% CI: 1.130-3.576, P = .018; HR = 1.701, 95% CI: 1.138-2.542, P = .010, respectively). Furthermore, subgroup analysis also detected a significant association between ABO blood group and ATLI in patients taking RIF (P < .05). However, no significant difference was observed in patients not taking RIF (P > .05).

WHAT IS NEW AND CONCLUSION

The present study is the first to evaluate the role of ABO blood group systems in Chinese ATLI cases. Based on the present matched case-control study, the ABO blood group may be associated with susceptibility to ATLI in the Chinese antituberculosis population, especially in patients with blood groups A, B and AB who are taking RIF.

摘要

已知和目的

抗结核药物性肝损伤(ATLI)是一种严重的药物不良反应,其发病机制在很大程度上仍不清楚。利福平(RIF)已被报道由于产生药物依赖性抗体而导致溶血,而溶血导致游离血红素水平升高,这影响了肝细胞的功能。血型决定簇可以作为药物-抗体复合物的特异性受体部位,在存在利福平的情况下导致红细胞破坏。RIF 诱导的免疫性溶血性贫血可能是 ATLI 的潜在机制。因此,本研究旨在探讨 ABO 血型系统在中国 ATLI 患者中的作用。

方法

在 146 例 ATLI 病例和 584 例对照中进行了 1:4 配比的病例对照研究。多变量条件逻辑回归和 Cox 比例风险回归用于估计 ABO 血型与 ATLI 风险之间的关联,通过比值比(OR)、风险比(HR)和 95%置信区间(CI)进行估计,并用肝病史和服用保肝药作为协变量。

结果和讨论

与 O 血型相比,A、B、AB 和非 O 血型的患者发生 ATLI 的风险显著增加(OR=1.832,95%CI:1.126-2.983,P=0.015;OR=1.751,95%CI:1.044-2.937,P=0.034;OR=2.059,95%CI:1.077-3.938,P=0.029;OR=1.822,95%CI:1.173-2.831,P=0.007)。在考虑 ALTI 发生时间后,A、B、AB 和非 O 血型组也发现了类似的结果(HR=1.676,95%CI:1.072-2.620,P=0.024;HR=1.620,95%CI:1.016-2.584,P=0.043;HR=2.010,95%CI:1.130-3.576,P=0.018;HR=1.701,95%CI:1.138-2.542,P=0.010)。此外,亚组分析还检测到在服用利福平的患者中 ABO 血型与 ATLI 之间存在显著关联(P<0.05)。然而,在未服用利福平的患者中未观察到显著差异(P>0.05)。

创新与结论

本研究首次评估了 ABO 血型系统在中国 ATLI 病例中的作用。基于本匹配病例对照研究,ABO 血型可能与中国抗结核人群中 ATLI 的易感性相关,尤其是在服用利福平的 A、B 和 AB 血型患者中。

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