Schmeltzer Paul A, Kosinski Andrzej S, Kleiner David E, Hoofnagle Jay H, Stolz Andrew, Fontana Robert J, Russo Mark W
Division of Hepatology, Carolinas Medical Center, Charlotte, NC, USA.
Duke Clinical Research Institute, Duke University, Durham, NC, USA.
Liver Int. 2016 Apr;36(4):603-9. doi: 10.1111/liv.13032. Epub 2015 Dec 15.
BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used and have been associated with hepatotoxicity. Studies of liver injury from NSAIDs have been retrospective and prospective data are lacking. The aim was to report the features and outcomes of the subjects with severe drug-induced liver injury from NSAIDS.
The U.S. Drug Induced Liver Injury Network is a prospective registry of idiosyncratic drug hepatotoxicity. All patients are evaluated in a standard fashion and followed up for at least 6 months.
Of 1221 Drug Induced Liver Injury Network cases that were adjudicated, 30 cases were attributed to eight different NSAIDs. The mean age was 52 years old, 24 (80%) were women, and 21 (70%) were Caucasian. The mean latency was 67 days. Common signs and symptoms at presentation were nausea (73%), jaundice (67%) and dark urine (67%). Mean peak serum aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase were 898 U/L, 1060 U/L, 12.2 mg/dl and 326 U/L. The most common pattern of injury was hepatocellular (70%) and autoantibodies were detected in 33% of cases. Diclofenac, was the most frequently implicated NSAID (16/30 cases), and characterized by hepatocellular injury. Seventeen cases resulted in hospitalization or prolongation of hospitalization and one patient died from complications of Stevens-Johnson syndrome because of diclofenac.
Hepatocellular injury is the most common pattern seen with NSAID hepatotoxicity, and diclofenac is the most frequently implicated agent. Given the number of NSAID alternatives, diclofenac should be reserved for patients who fail other NSAIDs and a high level of suspicion for hepatotoxicity should be maintained.
非甾体抗炎药（NSAIDs）被广泛使用，且与肝毒性有关。关于NSAIDs所致肝损伤的研究多为回顾性研究，缺乏前瞻性数据。本研究旨在报告NSAIDs所致严重药物性肝损伤患者的特征及转归。
美国药物性肝损伤网络是一个关于特异质性药物肝毒性的前瞻性注册研究。所有患者均按标准方式进行评估，并随访至少6个月。
在1221例经判定的药物性肝损伤网络病例中，30例归因于8种不同的NSAIDs。患者平均年龄为52岁，24例（80%）为女性，21例（70%）为白种人。平均潜伏期为67天。就诊时常见的体征和症状为恶心（73%）、黄疸（67%）和尿色加深（67%）。血清天冬氨酸氨基转移酶、丙氨酸氨基转移酶、总胆红素和碱性磷酸酶的平均峰值分别为898 U/L、1060 U/L、12.2 mg/dl和326 U/L。最常见的损伤类型为肝细胞损伤（70%），33%的病例检测到自身抗体。双氯芬酸是最常涉及的NSAID（16/30例），其特征为肝细胞损伤。17例患者需要住院治疗或住院时间延长，1例患者因双氯芬酸导致的史蒂文斯-约翰逊综合征并发症死亡。
肝细胞损伤是NSAIDs肝毒性最常见的类型，双氯芬酸是最常涉及的药物。鉴于有多种NSAIDs可供选择，双氯芬酸应仅用于对其他NSAIDs治疗无效的患者，且应高度怀疑其肝毒性。
