Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study.
Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study.
复制标题
DOI：
10.1053/j.gastro.2015.03.006
复制
发表时间：
2015-06
期刊：
影响因子：
29.4
通讯作者：
United States Drug Induced Liver Injury Network
中科院分区：
文献类型：
--
作者：
Chalasani N;Bonkovsky HL;Fontana R;Lee W;Stolz A;Talwalkar J;Reddy KR;Watkins PB;Navarro V;Barnhart H;Gu J;Serrano J;United States Drug Induced Liver Injury Network
药物性肝损伤网络 (DILIN) 正在美国对 DILI 患者进行一项前瞻性研究。我们展示了首批 1257 名参与该研究的患者的特征和亚组分析。在一项观察性纵向研究中，我们于 2004 年开始收集符合资格的疑似 DILI 个体的数据，并对他们进行了 6 个月或更长时间的跟踪。对受试者的其他病因、原因和 DILI 的严重程度进行系统评估。在 1257 名疑似 DILI 的入组受试者中，对 1091 名患者进行了因果关系评估，其中 899 名患者被认为患有明确的、高度可能的或可能的 DILI。 10% 的患者死亡或接受肝移植，17% 患有慢性肝损伤。在 89 名既往患有肝病的患者 (10%) 中，DILI 似乎比没有肝病的患者更严重（差异无统计学意义；P=.09），死亡率显着更高（16% vs 5.2%；P<.001）。与没有肝病的患者相比，阿奇霉素在患有既往肝病的患者中所占比例较高（6.7% vs. 1.5%，p=0.006）。 41 例潜伏期≤ 7 天的病例主要由抗菌药物引起（71%）。 60 例潜伏期 > 365 天的 DILI 病例的两个最常见原因是呋喃妥因 (25%) 或米诺环素 (17%)。 DILI 潜伏期短与长的患者的结局没有差异。与 65 岁以下的个体相比，65 岁或以上的个体 (n=149) 更容易出现胆汁淤积性损伤，尽管死亡率和肝移植率没有差异。九名患者（1%）伴有严重皮肤反应；涉及的药物包括拉莫三嗪、阿奇霉素、卡马西平、莫西沙星、头孢氨苄、双氯芬酸和呋喃妥因。其中四名患者死亡。与没有肝病或伴有严重皮肤反应的患者相比，药物性肝损伤的死亡率明显更高。需要进一步的研究来证实阿奇霉素与慢性肝病患者 DILI 增加之间的关联。年龄较大和潜伏期短或长与 DILI 死亡率无关。
The drug-induced liver injury network (DILIN) is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study. In an observational longitudinal study, we began collecting data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer. Subjects were evaluated systematically for other etiologies, causes, and severity of DILI. Among 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 899 were considered to have definite, highly likely, or probable DILI. Ten percent of patients died or underwent liver transplantation and 17% had chronic liver injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (difference not statistically significant; P=.09) and mortality was significantly higher (16% vs 5.2%; P<.001). Azithromycin was the implicated agent in a higher proportion of patients with pre-existing liver disease compared to those without liver disease (6.7% vs. 1.5%, p=0.006). Forty-one cases with latency ≤ 7 days were caused predominantly by antimicrobial agents (71%). Two most common causes for 60 DILI cases with latency >365 days were nitrofurantoin (25%) or minocycline (17%). There were no differences in outcomes of patients with short vs long latency of DILI. Compared to individuals younger than 65 y, individuals 65 y or older (n=149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. Nine patients (1%) had concomitant severe skin reactions; implicated agents were lamotrigine, azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and nitrofurantoin. Four of these patients died. Mortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared to patients without. Further studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. Older age and short or long latencies are not associated with DILI mortality.
登录
查看更多内容
影响因子：
13.5
作者：
Isabel Lucena, M.;Andrade, Raul J.;Avila, Susana
通讯作者：
Avila, Susana
影响因子：
5.1
作者：
Lee WM
通讯作者：
Lee WM
影响因子：
13.5
作者：
Isabel Lucena, M.;Andrade, Raul J.;Hidalgo, Ramon
通讯作者：
Hidalgo, Ramon
影响因子：
2.9
作者：
Ghabril, Marwan;Fontana, Robert;Chalasani, Naga
通讯作者：
Chalasani, Naga
影响因子：
4.2
作者：
Fontana RJ;Watkins PB;Bonkovsky HL;Chalasani N;Davern T;Serrano J;Rochon J;DILIN Study Group
通讯作者：
DILIN Study Group