498例药物性肝损伤患者的临床特点及其预后分析

Clinical characteristics and prognosis analysis of 498 cases with drug-induced liver injury

目的回顾性分析药物性肝损伤(DILI)患者的临床资料,以确定DILI的危险因素、临床特征及其治疗预后,为临床医师在DILI的诊断、治疗及其预防方面提供参考依据。方法收集2013年至2019年在昆明医科大学第二附属医院712例确诊的DILI病例的数据,其中498例纳入研究。收集所有患者的病史,临床表现与分型,实验室检查指标,疾病严重程度及病死率等数据。采用t检验、Mann-Whitney U检验/Pearsonχ^(2)检验/Fisher确切概率法或Spearman秩检验进行统计学分析。结果导致DILI的可疑药物中,单一用药占89.56%,主要有中药(56.43%)、抗肿瘤及免疫调节剂(8.03%)、抗感染药物(4.42%)、解热镇痛药物(4.22%)等,联合用药占10.44%。临床分型以肝细胞损伤型为主(63.05%),年龄段在临床分型中差异有统计学意义(P<0.001);不同药物导致的DILI中,年龄、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)、总胆汁酸(TBA)在不同可疑药物种类中差异有统计学意义(P值分别为<0.001、0.003、0.001、<0.001、<0.001);实验室检查结果显示ALT、AST、ALP、γ-谷氨酰转移酶(GGT)、TBA、国际标准化比值(INR)、嗜酸性粒细胞差异有统计学意义(P值分别<0.001、<0.001、<0.001、<0.001、0.018、0.003、0.019)。54例完善肝活检病理组织学检查的患者以慢性肝炎型多见,西药组纤维化高于中草药组,差异有统计学意义(P<0.05)。96.99%的DILI患者治愈或者好转,3.01%的患者未治愈。有序分类logistic回归分析表明,GGT、INR为预后不良的独立预测因子。结论DILI的可疑用药以草药/膳食补充剂、抗肿瘤及免疫调节剂、抗感染药物、解热镇痛药物常见,临床分型以肝细胞损伤型多见,多数DILI患者停药后预后良好,GGT、INR为预后不良的独立预测因子。

Objective To determine the risk factors,clinical characteristics and treatment prognosis,so as to provide reference for clinicians to diagnose,treat and prevent drug-induced liver injury(DILI).Methods Data of 712 confirmed DILI cases were collected from the Second Affiliated Hospital of Kunming Medical University between 2013 to 2019.Among them,498 cases were included in the study.All patients medical history,clinical manifestations and classification,laboratory parameters,disease severity,and mortality rate were collected.Statistical analysis was performed using t-test,Mann-Whitney U test/Pearsonχ^(2) test/Fisher's exact test or Spearman's rank test.Results Among the suspicious drugs causing DILI,single medication accounted for 89.56%,mainly including traditional Chinese medicine(56.43%),anti-tumor and immunomodulatory agents(8.03%),anti-infective drugs(4.42%),antipyretic and analgesic drugs(4.22%)%),etc.,while combination medication accounted for 10.44%.The clinical classification was dominated with hepatocyte injury(63.05%),and there was a statistically significant difference in clinical classification among age groups(P<0.001).Age,alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)and total bile acid(TBA)had statistically significant difference among different suspicious drugs in DILI caused by different drug(P<0.001,0.003,0.001,<0.001 and<0.001).Laboratory test results showed that there were statistically significant differences in ALT,AST,ALP,γ-glutamyltransferase(GGT),TBA,international normalized ratio(INR),and eosinophils(P<0.001,<0.001,<0.001,0.018,0.003 and 0.019,respectively).Chronic hepatitis was more common in the 54 cases who completed histopathological examination of the liver biopsy.Fibrosis degree was higher in the Western medicine group than Chinese herbal medicine group(P<0.05),and the difference was statistically significant(P<0.05).96.99%of DILI patients were cured or improved,and 3.01%of patients were uncured.Ordinal logistic regression analysis showed that GGT and INR were independent predictors of poor prognosis.Conclusions Suspicious drugs for DILI are herbal/dietary supplements,anti-tumor and immunomodulatory,anti-infective,and antipyretic and analgesic.The most common clinical classification is hepatocyte injury.Most patients with DILI have a good prognosis after drug withdrawal and GGT and INR are independent predictors of poor prognosis.