综合医院住院患者药物性肝损伤发生致病药物及影响肝损伤严重程度的因素分析*

doi:10.3969/j.issn.1672-5069.2023.05.017

摘要/Abstract

摘要： 目的调查住院患者药物性肝损伤(DILI)发生的致病药物并分析影响肝损伤严重程度的危险因素。方法 2018年9月～2022年3月我院诊治的DILI患者104例和同期住院的非DILI患者148例,根据《药物性肝损伤诊治指南》标准进行肝损伤程度分级,部分患者接受肝穿刺检查。应用单因素和多因素Logistic回归分析影响肝损伤程度的危险因素。结果本组DILI患者致病药物包括中草药39例(37.5%)、抗生素类17例(16.3%)、非甾体抗炎药13例(12.5%)、治疗心血管疾病药物8例(7.7%)、抗风湿药物7例(6.7%)、消化系统药物7例(6.7%)、精神类药物5例(4.8%)和内分泌疾病用药2例(1.9%);17例接受肝穿刺活检患者肝组织病理学表现包括肝细胞气球样变性11例(64.7%)、点灶状坏死10例(58.8%)、桥接坏死4例(23.5%)、汇管区淋巴细胞、浆细胞和中性粒细胞浸润15例(88.2%)、肝细胞内淤胆或胆栓形成5例(29.4%)和肝细胞玫瑰花结形成1例(5.9%);DILI组高血压和血脂异常发生率为17.3%和34.6%,显著高于非DILI组的8.1%和18.2% (P<0.05);DILI组主要表现为血清ALT、AST、GGT、ALP、TBIL、TG和TC水平升高;单因素分析显示,血脂异常【OR=2.17,95%CI(1.39～3.40),P=0.001】是DILI发生的独立危险因素;在104例DILI患者中,肝损伤程度≤2级80例,≥3级24例;多因素Logistic分析发现血脂异常【OR=3.10,95%CI(1.34～7.11)】和用药时间【OR=0.26,95%CI(0.08～0.80)】是影响DILI患者肝损伤程度的独立危险因素(P<0.05)。结论在综合医院,中草药、抗生素类和非甾体类抗炎药物是DILI发生的主要药物,多种基础疾病和血脂升高者更容易发生DILI,需要在临床上加强防治和干预,以减少DILI的发生。

关键词: 药物性肝损伤, 中草药, 抗生素类, 血脂异常, 肝损伤程度, 多因素分析

Abstract: Objective The purpose of this study was to investigate the common medicines and influencing factors on severity of liver injury in hospital stay patients with drug-induced liver injury (DILI). Methods 104 patients with DILI and 148 patients without DILI were encountered in our hospital between September 2018 and March 2022, and the severity of liver injury was evaluated based on guideline related. Some patients received liver biopsies. The influencing factors on the severity of liver injury was predicted by univariate and multivariate Logistic analysis. Results The alleged causative medicines in our series included Chinese herbal medicines in 39 cases (37.5%), antibiotics in 17 cases (16.3%), non-steroidal anti-inflammatory drugs in 13 cases (12.5%), cardiovascular drugs in 8 cases (7.7%), antirheumatic drugs in 7 cases (6.7%), digestive agents in 7 cases (6.7%), psychotropic drugs in 5 cases (4.8%) and endocrine drugs in 2 cases (1.9%); in 17 patients with DILI having liver biopsies, the liver histopathological examination showed hepatocyte balloon degeneration in 11 cases (64.7%), punctate necrosis in 10 cases (58.8%), bridging necrosis in 4 cases (23.5%), inflammatory cell infiltration in portal area in 15 cases (88.2%), intrahepatocyte cholestasis or bile embolus formation in 5 cases (29.4%), and hepatocyte rose knot in 1 case (5.9%); the incidences of blood hypertension and hyperlipoidemia in patients with DILI were 17.3% and 34.6%, muchhigher than 8.1% and 18.2% (P<0.05) in patients without DILI; serum ALT, AST, GGT, ALP, bilirubin, TG and TC levels in patients with DILI increased greatly in our series; the univariate Logistic analysis showed that the hyperlipoidemia [OR=2.17, 95%CI(1.39-3.40), P=0.001] was the independent factor for the happening of DILI; out of the 104 patients with DILI, it was found that the severity of liver injury ≤grade 2 in 80 cases, and ≥grade 3 in 24 cases; the multivariate Logistic analysis demonstrated that the hyperlipoidemia [OR=3.10, 95%CI(1.34-7.11)] and the period of medicine administered [OR=0.26, 95%CI(0.08-0.80)] were the independent risk factors for the severity of liver injury (P<0.05). Conclusion The common causative medicines for DILI in a general hospital in China are Chinese herbal medicines, antibiotics and non-steroidal anti-inflammatory drugs, and the patients with multi-systemic underlying diseases and hyperlipoidemia are prone to having DILI, which should be carefully dealt with in clinical practice.

Key words: Drug-induced liver injury, Chinese herbal medicines, Antibiotics, Hyperlipoidemia, Multivariate Logistic analysis

裴素娟, 郭锦辉, 魏晓霞. 综合医院住院患者药物性肝损伤发生致病药物及影响肝损伤严重程度的因素分析^*[J]. 实用肝脏病杂志, 2023, 26(5): 670-673.

Pei Sujuan, Guo Jinhui, Wei Xiaoxia. Common medicines and influencing factors on severity of liver injury in hospital stay patients with drug-induced liver injury[J]. Journal of Practical Hepatology, 2023, 26(5): 670-673.

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综合医院住院患者药物性肝损伤发生致病药物及影响肝损伤严重程度的因素分析^*

Common medicines and influencing factors on severity of liver injury in hospital stay patients with drug-induced liver injury

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