Biomarkers that are able to identify patients at risk of drug-induced liver injury (DILI) after treatment with infliximab could be important in increasing the safety of infliximab use. We performed a genetic analysis to identify possible human leukocyte antigen (HLA) associations with DILI in European Caucasian users of infliximab in a retrospective study of 16 infliximab-DILI patients and 60 matched controls. In infliximab-associated liver injury, multiple potentially causal individual HLA associations were observed, as well as possible haplotypes. The strongest associated HLA allele was HLA-B*39:01 (P = 0.001; odds ratio [OR] 43.6; 95% confidence interval [CI] 2.8-infinity), which always appeared with another associated allele C*12:03 (P = 0.032; OR 6.1; 95% CI 0.9-47.4). Other associations were observed with HLAs DQB1*02:01 (P = 0.007; OR 5.7; 95% CI 1.4-24.8), DRB1*03:01 (P = 0.012; OR 4.9; 95% CI 1.2-20.5), and B*08:01 (P = 0.048; OR 3.4; 95% CI 0.9-13.2), which also appeared together whenever present in cases. Additional associations were found with HLA-DPB1*10:01 (P = 0.042; OR 20.9; 95% CI 0.7-infinity) and HLA-DRB1*04:04 (P = 0.042; OR 20.9; 95% CI 0.7-infinity). A strong association with HLA-B*39:01 was identified as a potentially causal risk factor for infliximab-induced DILI. Future work should aim to validate this finding and explore possible mechanisms through which the biologic interacts with this particular allele.

中文翻译：

---

HLA与英夫利昔单抗引起的肝损伤相关。

能够识别英夫利昔单抗治疗后有药物诱发性肝损伤（DILI）风险的患者的生物标志物可能对提高英夫利昔单抗的使用安全性至关重要。我们对16名英夫利昔单抗-DILI患者和60位相匹配的对照组进行了回顾性研究，我们进行了遗传分析，以确定欧洲人英夫利昔单抗的白种人使用者中可能与DILI相关的人类白细胞抗原（HLA）关联。在英夫利昔单抗相关的肝损伤中，观察到多个潜在的因果关系的个体HLA关联，以及可能的单倍型。与HLA相关的最强等位基因是HLA-B * 39：01（P = 0.001；优势比[OR] 43.6； 95％置信区间[CI] 2.8-无穷大），它总是与另一个相关等位基因C * 12：03一起出现（ P = 0.032； OR 6.1； 95％CI 0.9-47.4）。观察到与HLA DQB1 * 02：01的其他关联（P = 0.007; OR 5.7; 95％CI 1.4-24.8），DRB1 * 03：01（P = 0.012; OR 4.9; 95％CI 1.2-20.5）和B * 08：01（P = 0.048; OR 3.4; 95％CI 0.9-13.2） ，也可以在案件中同时出现。还发现了与HLA-DPB1 * 10：01（P = 0.042; OR 20.9; 95％CI 0.7-infinity）和HLA-DRB1 * 04：04（P = 0.042; OR 20.9; 95％CI 0.7-infinity）的其他关联。与HLA-B * 39：01的强关联被确定为英夫利昔单抗诱导的DILI的潜在致病危险因素。未来的工作应旨在验证这一发现并探索生物与特定等位基因相互作用的可能机制。7-无穷大）和HLA-DRB1 * 04：04（P = 0.042; OR 20.9; 95％CI 0.7-无穷大）。与HLA-B * 39：01的强关联被确定为英夫利昔单抗诱导的DILI的潜在致病危险因素。未来的工作应旨在验证这一发现并探索生物与特定等位基因相互作用的可能机制。7-无穷大）和HLA-DRB1 * 04：04（P = 0.042; OR 20.9; 95％CI 0.7-无穷大）。与HLA-B * 39：01的强关联被确定为英夫利昔单抗诱导的DILI的潜在致病危险因素。未来的工作应旨在验证这一发现并探索生物与特定等位基因相互作用的可能机制。