Severe azathioprine-induced liver injury 22 months after initiation of treatment

Giovanni Cataletti, Fabrizio Santagata, Luca Pastorelli, Pier Maria Battezzati
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Abstract

Drug-induced liver injury (DILI) is the leading cause of acute liver failure in high-income countries. Acute cholestasis is one of the most common forms of hepatotoxicity induced by azathioprine. It usually begins during the first year of treatment, with most cases reported during the first month. We describe an uncommon case of DILI that occurred after 22 months of drug administration. A woman in her 50s was hospitalised because of jaundice and asthenia. She had been treated with azathioprine for myasthenia gravis during the last 2 years. Acute cholestatic injury was diagnosed. After ruling out most common causes of cholestasis, azathioprine was withdrawn and subsequent histological findings in liver biopsy were consistent with drug-induced cholestatic liver damage. After discontinuation of azathioprine, biochemical parameters progressively normalised and remarkable clinical improvement was achieved. With this report, we suggest that azathioprine should be considered among the causes of liver injury, despite long treatment duration. Drug-induced liver injury (DILI) is the most common cause of acute liver failure in high-income countries.1 Most cases are idiosyncratic and involve immune-mediated mechanisms which are independent of the dose used. In population-based studies, the incidence of DILI ranges between 13.9 and 19.1 cases per 100.000 people per year,1 a figure likely flawed by systematic under-reporting. Identification of the liable drug and its prompt discontinuation are critical to achieve patient recovery. Azathioprine is an immunosuppressive drug that works by inhibiting lymphocyte proliferation, thus limiting inflammatory and autoimmune responses. Azathioprine is a well-known cause of DILI, with an incidence of 1 case per 1103 users.2 Most cases of azathioprine-induced liver injury have been reported between the first month3 4 and the first year5–12 of treatment, while only a few cases of DILI have been described in long-term users of azathioprine.13 14 In the present …
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开始治疗 22 个月后,硫唑嘌呤诱发严重肝损伤
在高收入国家,药物性肝损伤(DILI)是导致急性肝功能衰竭的主要原因。急性胆汁淤积是硫唑嘌呤诱发的最常见肝毒性形式之一。急性胆汁淤积症通常发生在治疗的第一年,大多数病例发生在治疗的第一个月。我们描述了一例不常见的 DILI 病例,该病例是在用药 22 个月后发生的。一名 50 多岁的妇女因黄疸和气喘住院。在过去两年中,她一直在使用硫唑嘌呤治疗肌无力。诊断结果为急性胆汁淤积性损伤。在排除了最常见的胆汁淤积原因后,她停用了硫唑嘌呤,随后的肝活检组织学结果与药物引起的胆汁淤积性肝损伤一致。停用硫唑嘌呤后,生化指标逐渐恢复正常,临床症状也得到显著改善。通过本报告,我们认为,尽管硫唑嘌呤的治疗时间较长,但仍应将其视为肝损伤的原因之一。在高收入国家,药物性肝损伤(DILI)是急性肝功能衰竭最常见的原因。1 大多数病例具有特异性,涉及免疫介导机制,与用药剂量无关。在基于人口的研究中,DILI 的发病率介于每年每 10 万人 13.9 例至 19.1 例之间,1 这一数字很可能因系统性漏报而存在缺陷。确定致病药物并及时停药对患者的康复至关重要。硫唑嘌呤是一种免疫抑制剂,通过抑制淋巴细胞增殖发挥作用,从而限制炎症和自身免疫反应。硫唑嘌呤是众所周知的导致 DILI 的原因,每 1103 例使用者中就有 1 例发病。2 大多数硫唑嘌呤诱发肝损伤的病例都是在治疗的第一个月3 4 到第一年5-12 之间报告的,而长期使用硫唑嘌呤的患者中仅有少数病例被描述为 DILI。
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来源期刊
Drug and Therapeutics Bulletin
Drug and Therapeutics Bulletin Medicine-Pharmacology (medical)
CiteScore
0.80
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0.00%
发文量
69
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