Einstein Medical Center, 5501 Old York Road, Philadelphia, Pennsylvania, 19141, USA.
Gastroenterology Associates, 4745 Ogletown Stanton Road, Medical Arts Building, Suite 134, Newark, Delaware, 19713, USA.
Drug Saf. 2017 Sep;40(9):783-787. doi: 10.1007/s40264-017-0547-9.
The population-based incidence rate of drug-induced liver injury (DILI) in the USA is not known. The Drug-Induced Liver Injury Network (DILIN) accrues cases of hepatotoxicity due to medications and herbal and dietary supplements (HDS) from limited geographical areas. The current analysis was an ancillary study of DILIN aimed at determining the annual incidence of DILI in the USA on a population basis, through surveillance in the state of Delaware.
At the outset of the study, there were 41 gastroenterologists in the state of Delaware and all agreed to participate in surveillance for DILI, which comprised active reporting of suspected cases to the DILIN. The gastroenterologists underwent training in the diagnosis of DILI and were provided with DILIN inclusion criteria. Only cases that met the DILIN laboratory inclusion criteria in 2014 were included in the incidence calculation, and these patients were invited to participate in the DILIN Prospective Study. The number of suspected cases that met inclusion criteria served as the numerator and the 2014 Delaware adult population as the denominator.
During 2014, 23 patients were identified by the surveillance network, 20 of whom met DILIN laboratory inclusion criteria, leading to an incidence of 2.7 cases of DILI per 100,000 adult residents [95% confidence interval (CI) 1.5-3.9 per 100,000]. Fourteen subjects agreed to participate in the DILIN; six declined. Among enrolled cases, the mean age was 51 years, 57% were women, and 71% were white. Eight cases were attributed to antibiotics (36%) and other drugs (21%) and six to HDS (43%). The pattern of injury was hepatocellular in all HDS cases, but only 50% of conventional drug cases (p = 0.05), which more commonly presented with eosinophilia (p = 0.47) and higher alkaline phosphatase levels (p = 0.05). Half of patients were jaundiced, none developed liver failure, and all recovered without the need for transplantation.
Prospective, gastroenterologist-based surveillance for suspected DILI in Delaware yielded an incidence of 2.7 cases per 100,000 adults in 2014; this is the first prospective estimate of DILI for the USA. Because surveillance was limited to subspecialists, the actual incidence of DILI is likely to be higher. These findings provide a benchmark statistic for the epidemiology of DILI in the United States, to be refined with expansion of the surveillance period.
美国人群中药物性肝损伤（DILI）的基于人群的发病率尚不清楚。药物性肝损伤网络（DILIN）从有限的地理区域内收集因药物和草药及膳食补充剂（HDS）导致的肝毒性病例。本分析是 DILIN 的一项辅助研究，旨在通过在特拉华州进行监测，确定美国人群中基于人群的 DILI 年发病率。
研究开始时，特拉华州有 41 名胃肠病学家，他们均同意参与 DILI 的监测，包括向 DILIN 主动报告疑似病例。胃肠病学家接受了 DILI 诊断方面的培训，并获得了 DILIN 的纳入标准。仅纳入符合 2014 年 DILIN 实验室纳入标准的病例进行发病率计算，并邀请这些患者参加 DILIN 前瞻性研究。符合纳入标准的疑似病例数量作为分子，2014 年特拉华州成年居民数量作为分母。
2014 年，监测网络共发现 23 例患者，其中 20 例符合 DILIN 实验室纳入标准，导致每 10 万成年居民中有 2.7 例 DILI（95%置信区间为每 10 万居民 1.5-3.9）。14 例患者同意参加 DILIN，6 例拒绝。纳入病例的平均年龄为 51 岁，57%为女性，71%为白人。8 例归因于抗生素（36%）和其他药物（21%），6 例归因于 HDS（43%）。所有 HDS 病例的损伤模式均为肝细胞性，而仅有 50%的常规药物病例（p=0.05）出现嗜酸性粒细胞增多（p=0.47）和更高的碱性磷酸酶水平（p=0.05）。半数患者出现黄疸，无患者发生肝功能衰竭，所有患者均康复，无需进行肝移植。
在特拉华州，以胃肠病学家为基础对疑似 DILI 进行前瞻性监测，2014 年的发病率为每 10 万成年人 2.7 例；这是美国 DILI 的首次前瞻性估计。由于监测仅限于亚专科医生，因此实际的 DILI 发病率可能更高。这些发现为美国 DILI 的流行病学提供了一个基准统计数据，随着监测时间的延长，这一数据将会得到进一步完善。
