Xiong Yu-Ting, Wang Jian-Fei, Niu Xiao-Xia, Fu Yi-Ming, Wang Ke-Xin, Wang Chun-Yan, Li Qian-Qian, Wang Jian-Jun, Zhao Jun, Ji Dong
Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
307 Clinical Medical College of PLA, Anhui Medical University, Beijing, China.
Front Pharmacol. 2023 Feb 16;14:1071709. doi: 10.3389/fphar.2023.1071709. eCollection 2023.
Drug-induced liver injury (DILI) is a potentially serious adverse drug reaction. Due to the lack of definite etiology, specific clinical manifestations, and diagnostic methods, its prediction and diagnosis are challenging. Elderly individuals are deemed to be at high risk for DILI due to abnormal pharmacokinetics, aging tissue repair function, comorbidities, and taking multiple drugs. This study aimed to identify the clinical characteristics and explore the risk factors associated with the severity of illness in elderly patients with DILI. In the present study, the clinical characteristics at the time of liver biopsy of consecutive patients with biopsy-proven DILI who presented at our hospital from June 2005 to September 2022 were evaluated. Hepatic inflammation and fibrosis were assessed according to the Scheuer scoring system. The presence of autoimmunity was considered if IgG level >1.1 × ULN (1826 mg/dL), or high titer (>1:80) of ANA, or SMA. In total, 441 patients were enrolled, and the median age was 63.3 years (IQR, 61.0-66.0); 122 (27.7%), 195 (44.2%), or 124 (28.1%) were classified as having minor, moderate, or severe hepatic inflammation, respectively; and 188 (42.6%), 210 (47.6%) or 43 (9.8%) patients presented minor, significant fibrosis or cirrhosis, respectively. Female sex (73.5%) and the cholestatic pattern (47.6%) were dominant in elderly DILI patients. Autoimmunity existed in 201 patients (45.6%). Comorbidities were not directly associated with the severity of DILI. PLT (OR: 0.994, 95% CI: 0.991-0.997; < 0.001), AST (OR: 1.001, 95% CI: 1.000-1.003, = 0.012), TBIL (OR: 1.006, 95% CI: 1.003-1.010, < 0.001), and autoimmunity (OR: 1.831, 95% CI: 1.258-2.672, = 0.002) were associated with the degree of hepatic inflammation. Meanwhile, PLT (OR: 0.990, 95% CI: 0.986-0.993, < 0.001), TBIL (OR: 1.004, 95% CI: 1.000-1.007, = 0.028), age (OR: 1.123, 95% CI: 1.067-1.183, < 0.001), and autoimmunity (OR: 1.760, 95% CI: 1.191-2.608, = 0.005) were associated with the stage of hepatic fibrosis. This study revealed that the presence of autoimmunity represents a more serious illness state of DILI, deserving more intensive monitoring and progressive treatment.
药物性肝损伤（DILI）是一种潜在的严重药物不良反应。由于缺乏明确的病因、特异性临床表现和诊断方法，其预测和诊断具有挑战性。由于药代动力学异常、组织修复功能老化、合并症以及服用多种药物，老年人被认为是发生DILI的高危人群。本研究旨在确定老年DILI患者的临床特征，并探索与疾病严重程度相关的危险因素。在本研究中，对2005年6月至2022年9月在我院就诊的经活检证实为DILI的连续患者进行肝活检时的临床特征进行了评估。根据Scheuer评分系统评估肝脏炎症和纤维化情况。如果IgG水平>1.1×ULN（1826mg/dL）、抗核抗体（ANA）高滴度（>1:80）或平滑肌抗体（SMA），则考虑存在自身免疫。共纳入441例患者，中位年龄为63.3岁（四分位间距，61.0 - 66.0）；分别有122例（27.7%）、195例（44.2%）或124例（28.1%）被分类为轻度、中度或重度肝脏炎症；分别有188例（42.6%）、210例（47.6%）或43例（9.8%）患者表现为轻度、显著纤维化或肝硬化。女性（73.5%）和胆汁淤积型（47.6%）在老年DILI患者中占主导。201例患者（45.6%）存在自身免疫。合并症与DILI的严重程度无直接关联。血小板（PLT）（比值比[OR]：0.994，95%置信区间[CI]：0.991 - 0.997；P<0.001）、谷草转氨酶（AST）（OR：1.001，95%CI：1.000 - 1.003，P = 0.012）、总胆红素（TBIL）（OR：1.006，95%CI：1.003 - 1.010，P<0.001）和自身免疫（OR：1.831，95%CI：1.258 - 2.672，P = 0.002）与肝脏炎症程度相关。同时，PLT（OR：0.990，95%CI：0.986 - 0.993，P<0.001）、TBIL（OR：1.004，95%CI：1.000 - 1.007，P = 0.028）、年龄（OR：1.123，95%CI：1.067 - 1.183，P<0.001）和自身免疫（OR：1.760，95%CI：1.191 - 2.608，P = 0.005）与肝纤维化阶段相关。本研究表明，自身免疫的存在代表了DILI更严重的疾病状态，值得更密切的监测和积极的治疗。
