化疗药物所致肝损伤128例临床分析

Clinical analysis of 128 cases with liver injury caused by chemotherapy drugs

目的分析化疗药物所致药物性肝损伤(drug induced liver injury,DILI)的临床特点,为有效降低DILI发病率,减少病死率提供临床依据。方法根据2015年版《药物性肝损伤诊治指南》,收集我院2012年1月—2016年12月128例化疗药物所致DILI住院患者临床资料,分析化疗药物种类,出现DILI的时间、严重程度、治疗方式及临床效果。结果本组患者共128例,男性46例(30.51%),女性82例(69.49%),其中最小年龄24.0岁,最大82.0岁,平均(53.2±5.4)岁。使用化疗药物到发生肝损伤时间从2.0~30.0 d,平均(16.3±2.4)d。引起DILI的化疗药物主要有紫杉醇、铂类、环磷酰胺、阿霉素等,联合使用化疗药物可增加肝损伤的发生率及程度。本组患者中DILI的程度:1级(轻度肝损伤)74例(57.81%),2级(中度肝损伤)44例(34.38%),3级(重度肝损伤)8例(6.25%),4级(肝衰竭)1例(0.78%),5级(死亡)1例(0.78%)。治疗方式根据2007年版《急性药物肝损伤诊治建议》(草案):1级肝损伤患者继续使用化疗药物,同时应用口服多烯磷脂酰胆碱胶囊及甘草酸二铵肠溶胶囊;2级肝损伤给予多烯磷脂酰胆碱注射液、异甘草酸镁注射液静脉滴注;3级肝损伤给予多烯磷脂酰胆碱注射液、异甘草酸镁注射液、丁二磺腺苷蛋酸注射液静脉滴注,必要时使用激素及血浆置换。4级、5级除患者给予上述常规治疗外,适时给予激素及血浆置换。多数患者预后良好,治愈117例(91.40%),死亡1例(0.78%),慢性化发展为肝硬化2例(1.50%),放弃治疗8例(6.25%)。结论化疗药物所致DILI并不少见,接受化疗的患者常规监测肝功能,及时发现DILI并积极有效处理,绝大多数化疗所致DILI可治愈且预后良好。

Objective To analyze the clinical characteristics of drug-induced liver injury（DILI） caused by chemotherapeutic drugs, and to provide clinical data for effectively reducing the incidence and mortality of DILI. Methods According to the 2015 edition of Guidelines of Diagnosis and Treatment of Drug-Induced Liver Injury, 128 DILI cases from January 2012 to December 2016 in our hospital were included and their clinical data were collected. Type of chemotherapy drugs, DILI onset time, severity, treatment and clinical outcome were analyzed. Results There were 128 patients in this analysis, including 46 males（30.51%） and 82 females（69.49%）. The minimum age was 24-year, and the maximum age was 82-year, with an average of（53.2±5.4） year-old. The DILI onset time was from 2 to 30 days, with an average of（16.3±2.4） days. The main chemotherapeutic agents that caused DILI included paclitaxel, platinum, cyclophosphamide, adriamycin and so on. The combination of chemotherapy drugs increased the incidence and severity of liver injury. The severity of DILI included grade 1（mild liver injury） in 74 cases（57.81%）, grade 2（moderate liver injury） in 44 cases（34.38%）, grade 3（severe liver injury） in 8 cases（6.25%）, grade 4（liver failure） in 1 case（0.78%）, and grade 5（death） in 1 case（0.78%）. According to the 2015 edition of Guidelines of Diagnosis and Treatment of DILI, patients with grade 1 liver injury continued to use chemotherapuetic drugs, and meanwhile received oral polyene phosphatidylcholine capsule and diammonium glycyrrhizinate enteric-coated capsules. Patients with grade 2 liver injury were given intravenous injection of polyene phosphatidylcholine and magnesium isoglycyrrhizinate. Patients with grade 3 liver injury were intravenously injected with polyene phosphatidylcholine, magnesium isoglycyrrhizinate, and butadisulfonate adenosine. Glucocorticoid and plasma replacement can be also used if necessary. Patients in grade 4 and 5 were given glucocorticoid and plasma replacement besides conventional treatment. The majority of patients had good prognosis, of which 117 cases cured（91.40%）, 1 case died（0.78%）, 2 cases developed into chronic cirrhosis（1.5%）, and 8 cases gave up the treatment（6.25%）. Conclusions DILI caused by chemotherapy drugs is not uncommon. Liver function should be routinely monitored for patients receiving chemotherapy. DILI should be detected and treated actively and effectively. DILI caused by most chemotherapy can be cured and the prognosis is satisfied.