William J. von Leibig Transplant Center, Mayo Clinic, Rochester, MN 55905, USA.
Liver Transpl. 2012 Jul;18(7):803-10. doi: 10.1002/lt.23424.
Drug-induced liver injury (DILI) is increasingly being recognized as a common cause of acute hepatitis. The clinical impact of DILI after liver transplantation (LT) is not known. The aim of this study was to describe the frequency, clinical presentation, and outcomes of DILI in LT recipients. LT recipients with possible DILI were identified with electronic pathology records and clinical note database retrieval tools. Diagnostic criteria were applied to identify cases of DILI. Twenty-nine of 1689 LT recipients (1.7%) were identified with DILI. The mean age was 52 years, and 52% were women. The major indications for LT were primary sclerosing cholangitis (28%), cholangiocarcinoma (14%), and hepatocellular carcinoma (14%). The severity of DILI was mild or moderate in 92% of the cases. Nausea or diarrhea (31%), jaundice (24%), and pruritus (10%) were the most common symptoms at the time of diagnosis. The mean biochemistry values were as follows: alanine aminotransferase, 204 ± 263 U/L; aspartate aminotransferase, 108 ± 237 U/L; alkaline phosphatase, 469 ± 689 U/L; and total bilirubin, 1.9 ± 10.3 mg/dL. The median duration of medication use until the diagnosis of DILI was 57 days, and the major agent classes were antibiotics (48%), immunosuppressive agents (14%), and antihyperlipidemic drugs (7%). Trimethoprim-sulfamethoxazole was the most common implicated agent (n = 11). Serum liver enzymes improved within a median time of 34 days (range = 5-246 days) after drug withdrawal. Hepatic retransplantation or death did not occur. Among the 50 cases with possible DILI explained by other causes, 13 individuals (26%) had no alternative diagnosis despite histological findings compatible with DILI. In conclusion, DILI is a rare yet underrecognized event among LT recipients. The majority of cases are not clinically severe, and they resolve after drug cessation without hepatic retransplantation or death.
药物性肝损伤(DILI)日益被认为是急性肝炎的常见病因。肝移植(LT)后 DILI 的临床影响尚不清楚。本研究旨在描述 LT 受者中 DILI 的频率、临床表现和结局。通过电子病理记录和临床笔记数据库检索工具确定可能患有 DILI 的 LT 受者。应用诊断标准来确定 DILI 病例。在 1689 名 LT 受者中,有 29 名(1.7%)被诊断为 DILI。平均年龄为 52 岁,52%为女性。LT 的主要适应证是原发性硬化性胆管炎(28%)、胆管癌(14%)和肝细胞癌(14%)。92%的病例 DILI 严重程度为轻度或中度。诊断时最常见的症状是恶心或腹泻(31%)、黄疸(24%)和瘙痒(10%)。平均生化值如下:丙氨酸氨基转移酶 204±263 U/L;天冬氨酸氨基转移酶 108±237 U/L;碱性磷酸酶 469±689 U/L;总胆红素 1.9±10.3mg/dL。从开始用药到诊断 DILI 的时间中位数为 57 天,主要药物类别为抗生素(48%)、免疫抑制剂(14%)和降脂药(7%)。甲氧苄啶-磺胺甲噁唑是最常见的可疑药物(n=11)。停药后中位 34 天(范围 5-246 天)血清肝酶恢复正常。未发生肝再移植或死亡。在 50 例可能由其他原因引起的 DILI 中,尽管组织学发现符合 DILI,但仍有 13 人(26%)无其他诊断。总之,DILI 是 LT 受者中罕见但未被认识到的事件。大多数病例并不严重,停药后无需肝再移植或死亡即可缓解。