DICLOFENAC-ASSOCIATED HEPATOTOXICITY - ANALYSIS OF 180 CASES REPORTED TO THE FOOD-AND-DRUG-ADMINISTRATION AS ADVERSE REACTIONS
DICLOFENAC-ASSOCIATED HEPATOTOXICITY - ANALYSIS OF 180 CASES REPORTED TO THE FOOD-AND-DRUG-ADMINISTRATION AS ADVERSE REACTIONS
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DOI：
10.1002/hep.1840220320
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发表时间：
1995-09-01
期刊：
影响因子：
13.5
通讯作者：
HARTER, JG
中科院分区：
文献类型：
--
作者：
BANKS, AT;ZIMMERMAN, HJ;HARTER, JG
双氯芬酸是一种非甾体抗炎药，于1988年在美国获批用于治疗骨关节炎、类风湿性关节炎或强直性脊柱炎患者。为了描述其临床、生化和组织学特征以及与其使用相关的肝损伤的可能机制，对1988年11月至1991年6月期间向食品和药物管理局报告的180名患者进行了回顾性分析，这些患者可能对双氯芬酸产生了不良反应。在报告的 180 例病例中，79% 为女性，71% 为 60 岁或以上，77% 患有骨关节炎。百分之六十七的病例是通过症状发现的，其余的则是通过异常实验室检测发现的。 75% 有症状的患者（120 名患者中的 90 名）患有黄疸。 90 名黄疸患者中有 7 人死亡。 66% 的病例损伤生化类型为肝细胞性或混合性肝细胞性。只有 8% 有胆汁淤积性损伤。其余的，转氨酶和碱性磷酸酶值略有增加，被认为是“不确定的”，即轻度肝细胞或无黄疸的“胆汁淤积”损伤。 21 例患者的肝脏切片可供研究。 24% 的病例在开始用药后 1 个月、63% 的病例在 3 个月时、85% 的病例在 6 个月时出现明显肝损伤。 12%的潜伏期为6至12个月，而3%的潜伏期超过12个月。皮疹、发烧和嗜酸性粒细胞增多这些免疫特性（过敏）的所有特征在任何病例中都没有报告；此外，大多数患者的潜伏期较长，因此推断该机制可能是代谢特质。数据表明，双氯芬酸相关的肝损伤特别可能涉及骨关节炎女性，在开始使用双氯芬酸后 1 至 6 个月出现黄疸，损伤主要是肝细胞，可能是由代谢特性引起的。
Diclofenac is a nonsteroidal anti-inflammatory drug approved in the United States in 1988 for the treatment of patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis. To characterize the clinical, biochemical, and histological features and possible mechanisms of hepatic injury associated with its use, a retrospective analysis was undertaken of 180 patients whose cases were reported to the Food and Drug Administration from November 1988 through June 1991, as having had possible adverse reactions to diclofenac. Of the reported 180 cases, 79% were female, 71% were 60 years of age or older, and 77% had osteoarthritis. Sixty-seven percent of the cases were detected by symptoms and the remainder by abnormal laboratory tests. Seventy-five percent of the symptomatic patients (90 of 120) were jaundiced. Seven of the 90 icteric patients died. The biochemical pattern of injury was hepatocellular or mixed hepatocellular in 66% of cases. Only 8% had a pattern of cholestatic injury. The remainder, with modestly increased values of both transaminases and alkaline phosphatase, were considered ''indeterminate,'' i.e., either mild hepatocellular or anicteric ''cholestatic'' injury. Sections of liver from 21 cases were available for study. Hepatic injury was apparent by 1 month after starting the drug in 24%, by 3 months in 63%, and by 6 months in 85% of cases. The latent period in 12% was 6 to 12 months, whereas in 3% it was greater than 12 months. A combination of rash, fever, and eosinophilia, all hallmarks of immunological idiosyncrasy (hypersensitivity), was not reported in any case; additionally, the long latent period in most of the patients led to the inference that the mechanism is probably metabolic idiosyncrasy. The data suggest that diclofenac-related liver injury is particularly likely to involve osteoarthritic females, presenting with jaundice 1 to 6 months after starting diclofenac, with injury that is predominantly hepatocellular and presumably caused by metabolic idiosyncrasy.