Delgado Ana, Stewart Stefan, Urroz Mikel, Rodríguez Amelia, Borobia Alberto M, Akatbach-Bousaid Ibtissam, González-Muñoz Miguel, Ramírez Elena
Clinical Pharmacology Department, La Paz University Hospital-IdiPAZ, School of Medicine, Autonomous University of Madrid, 28046 Madrid, Spain.
Immunology Department, La Paz University Hospital-IdiPAZ, 28046 Madrid, Spain.
J Clin Med. 2021 Sep 27;10(19):4432. doi: 10.3390/jcm10194432.
Coronavirus disease 2019 (COVID-19) has a wide spectrum of clinical manifestations. An elevation of liver damage markers has been observed in numerous cases, which could be related to the empirical use of potentially hepatotoxic drugs. The aim of this study was to describe the clinical and analytical characteristics and perform a causality analysis from laboratory signals available of drug-induced liver injury (DILI) detected by a proactive pharmacovigilance program in patients hospitalised for COVID-19 at La Paz University Hospital in Madrid (Spain) from 1 March 2020 to 31 December 2020. The updated Roussel Uclaf Causality Assessment Method (RUCAM) was employed to assess DILI causality. A lymphocyte transformation test (LTT) was performed on 10 patients. Ultimately, 160 patients were included. The incidence of DILI (alanine aminotransferase >5, upper limit of normal) was 4.9%; of these, 60% had previous COVID-19 hepatitis, the stay was 8.1 days longer and 98.1% were being treated with more than 5 drugs. The most frequent mechanism was hepatocellular (57.5%), with mild severity (87.5%) and subsequent recovery (88.1%). The most commonly associated drugs were hydroxychloroquine, azithromycin, tocilizumab and ceftriaxone. The highest incidence rate of DILI per 10,000 defined daily doses (DDD) was with remdesivir (992.7/10,000 DDD). Some 80% of the LTTs performed were positive, with a RUCAM score of ≥4. The presence of DILI after COVID-19 was associated with longer hospital stays. An immune mechanism has been demonstrated in a small subset of DILI cases.
2019冠状病毒病（COVID-19）具有广泛的临床表现。在许多病例中观察到肝损伤标志物升高，这可能与经验性使用潜在肝毒性药物有关。本研究的目的是描述临床和分析特征，并根据马德里（西班牙）拉巴斯大学医院2020年3月1日至2020年12月31日因COVID-19住院患者的主动药物警戒计划检测到的药物性肝损伤（DILI）的实验室信号进行因果关系分析。采用更新后的鲁塞尔·乌克拉夫因果关系评估方法（RUCAM）评估DILI因果关系。对10例患者进行了淋巴细胞转化试验（LTT）。最终纳入160例患者。DILI（丙氨酸转氨酶>5倍正常上限）的发生率为4.9%；其中，60%既往有COVID-19肝炎，住院时间长8.1天，98.1%正在接受5种以上药物治疗。最常见的机制是肝细胞性（57.5%），严重程度为轻度（87.5%），随后恢复（88.1%）。最常相关的药物是羟氯喹、阿奇霉素、托珠单抗和头孢曲松。每10000定义日剂量（DDD）中DILI发生率最高的是瑞德西韦（992.7/10000 DDD）。约80%的LTT检测结果为阳性，RUCAM评分为≥4。COVID-19后发生DILI与住院时间延长有关。在一小部分DILI病例中已证实存在免疫机制。
