Objectives The efficacy of avacopan as remission induction therapy for Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)-associated vasculitis (AAV) is well-established. However, concerns regarding liver injury post-avacopan treatment remain, especially in Japan. Therefore, this study aimed to investigate drug-induced liver injury (DILI) associated with avacopan treatment. Methods This study included 22 patients with AAV who were treated with avacopan at multiple centers in Japan between September 2021 and March 2024. DILI was assessed by the Japanese version of a revised electronic causality assessment method (RECAM-J 2023). Results Among the 22 patients treated with avacopan, DILI was observed in nine cases (40.9%): six with microscopic polyangiitis and three with granulomatosis with polyangiitis. Severe DILI with elevated total bilirubin (T-Bil) was observed in four of the nine patients (44.4%), a few weeks after the initiation of avacopan therapy. Eight of the nine patients (88.9%) with DILI improved after discontinuation of avacopan and other medications, and one patient developed vanishing bile duct syndrome (VBDS) leading to death. Avacopan-induced DILI was classified into three patterns: 1, short-term injury without T-Bil elevation; 2, transient cholestatic liver injury with T-Bil elevation; 3, decompensated liver injury with marked T-Bil elevation (VBDS). The risk factors for severe DILI with T-Bil elevation in Japanese patients included older age, lower body mass index, and early onset DILI following the initiation of avacopan treatment. Conclusion Avacopan-induced DILI is relatively common in Japan and could be lethal. Frequent laboratory follow-ups should be considered, especially for elderly and low-body-weight patients.

中文翻译：

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与 avacopan 治疗相关的药物性肝损伤


目的 avacopan 作为抗中性粒细胞胞质自身抗体 （ANCA） 相关血管炎 （AAV） 缓解诱导治疗的疗效已得到公认。然而，对 avacopan 治疗后肝损伤的担忧仍然存在，尤其是在日本。因此，本研究旨在调查与 avacopan 治疗相关的药物性肝损伤 （DILI）。方法 本研究包括 2021 年 9 月至 2024 年 3 月期间在日本多个中心接受 avacopan 治疗的 22 例 AAV 患者。DILI 通过修订后的电子因果关系评估方法 （RECAM-J 2023） 的日文版进行评估。结果 在 22 例 avacopan 治疗患者中，9 例 （40.9%） 观察到 DILI： 6 例显微镜下多血管炎，3 例肉芽肿性多血管炎。在 avacopan 治疗开始几周后，9 名患者中有 4 名 （44.4%） 观察到严重 DILI 伴总胆红素 （T-Bil） 升高。9 例 DILI 患者中有 8 例 （88.9%） 在停用 avacopan 和其他药物后有所改善，1 例患者出现胆管消失综合征 （VBDS） 导致死亡。Avacopan 诱导的 DILI 分为 3 种模式： 1、短期损伤无 T-Bil 升高;2，一过性胆汁淤积性肝损伤伴 T-Bil 升高;3、失代偿性肝损伤伴显著的 T-Bil 升高 （VBDS）。日本患者严重 DILI 伴 T-Bil 升高的危险因素包括高龄、体重指数较低和开始 avacopan 治疗后早发性 DILI。结论 Avacopan 诱导的 DILI 在日本相对常见，并且可能是致命的。应考虑频繁的实验室随访，尤其是对于老年人和低体重患者。