Ahmad Jawad, Odin Joseph A, Hayashi Paul H, Chalasani Naga, Fontana Robert J, Barnhart Huiman, Cirulli Elizabeth T, Kleiner David E, Hoofnagle Jay H
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Dig Dis Sci. 2017 Dec;62(12):3596-3604. doi: 10.1007/s10620-017-4812-7. Epub 2017 Nov 8.
Fenofibrate is a commonly used hypolipidemic associated with rare instances of hepatotoxicity, and routine liver biochemistry monitoring is recommended.
The aim of this study is to describe the presenting clinical features, liver histopathology, and outcomes of 7 cases of acute liver injury associated with fenofibrate.
All cases of definite, very likely, and probable drug-induced liver injury (DILI) attributed to fenofibrate enrolled in the DILI Network study between 2004 and 2015 were reviewed.
Among 1229 patients with confirmed DILI, 7 cases (0.6%) were attributed to fenofibrate. The median age was 43 (range 37-61) years, and latency to onset was short (5-8 weeks) in 4 patients but more prolonged (18-56 weeks) in the rest. Laboratory results at presentation showed hepatocellular, mixed, and cholestatic injury, but 6 cases presented with jaundice. No patient had undergone routine monitoring. Four patients required hospitalization and 2 in whom drug discontinuation was delayed had a severe outcome, 1 undergoing liver transplantation, and 1 developing chronic injury and death. Liver biopsy was available in 4 patients and showed diverse injury patterns. Genetic studies showed the presence of the rare HLA-A*33:01 in 3 patients (43 vs. 1% in control populations). The causality scores were highly likely in 5 and probable in 2.
Liver injury after fenofibrate exposure occurs with variable latency, enzyme elevation, and histology. Although most cases are self-limited, severe injury and mortality can occur, particularly if drug withdrawal is delayed. Jaundice or abnormal laboratory tests during fenofibrate therapy should trigger prompt discontinuation.
非诺贝特是一种常用的降血脂药物，与罕见的肝毒性病例相关，因此建议进行常规肝脏生化监测。
本研究旨在描述7例与非诺贝特相关的急性肝损伤的临床表现、肝脏组织病理学及预后情况。
回顾了2004年至2015年期间在药物性肝损伤网络研究中纳入的所有明确、很可能和可能由非诺贝特引起的药物性肝损伤（DILI）病例。
在1229例确诊为DILI的患者中，7例（0.6%）归因于非诺贝特。中位年龄为43岁（范围37 - 61岁），4例患者发病潜伏期较短（5 - 8周），其余患者潜伏期较长（18 - 56周）。就诊时的实验室检查结果显示有肝细胞损伤、混合型损伤和胆汁淤积性损伤，但6例出现黄疸。无患者进行过常规监测。4例患者需要住院治疗，2例停药延迟的患者预后严重，1例接受了肝移植，1例发展为慢性损伤并死亡。4例患者进行了肝活检，显示出不同的损伤模式。基因研究表明，3例患者（43%）存在罕见的HLA - A*33:01（对照组为1%）。因果关系评分5例为很可能，2例为可能。
非诺贝特暴露后肝损伤的潜伏期、酶升高和组织学表现各不相同。虽然大多数病例是自限性的，但严重损伤和死亡仍可能发生，特别是在停药延迟的情况下。非诺贝特治疗期间出现黄疸或实验室检查异常应立即停药。
