糖皮质激素治疗重症药物性肝损伤的效果分析

Effect of glucocorticoid in the treatment of severe drug-induced liver injury

目的 探讨重症药物性肝损伤(DILI)患者应用糖皮质激素的治疗效果。方法 回顾性分析2019年1月—2021年9月山西医科大学第一医院收治的重症DILI患者资料,统计人口特征、肝损伤药物、临床表现,比较使用糖皮质激素治疗患者(激素组)与未使用激素患者(对照组)的肝功能变化、疗效及不良反应。计量资料两组间比较采用独立样本t检验或Mann-Whitney U检验。计数资料组间比较采用χ^(2)检验或Fisher精确检验。结果 共纳入88例DILI患者,其中男33例,女55例,中位年龄49岁;对照组61例,激素组27例。临床分型以肝细胞损伤型为主;肝损伤药物中,中药和膳食补充剂最为常见。临床表现以黄疸、恶心、纳差居多,6例患者(6.82%,6/88)进展为4级DILI,其中激素组2例,对照组4例。激素组与对照组患者基线特征比较,AST、GGT、TBil及免疫指标阳性占比差异均有统计学意义(P值均<0.05)。两组治疗3 d时TBil、INR及TBA下降率比较,差异均有统计学意义(P值均<0.05);治疗7 d时,两组ALT、GGT、INR和TBA下降率差异均有统计学意义(P值均<0.05)。激素组治疗3 d(59.26%vs 29.51%,χ^(2)=55.82,P=0.008)和治疗7 d(81.48%vs 29.51%,χ^(2)=64.27,P<0.001)的累计有效率均明显高于对照组。激素组中2例4级重症DILI患者治疗均无效,而因常规保肝治疗后肝酶下降但胆红素持续升高或降低不明显而加用激素的患者中93.75%治疗有效。结论 中药及膳食补充剂是最常见的肝损伤药物。对于常规治疗后胆红素降低不理想的3级DILI患者短期内使用激素可获益。

Objective To investigate the therapeutic effect of glucocorticoid in patients with severe drug-induced liver injury(DILI).Methods A retrospective analysis was performed for the data of patients with severe DILI who were admitted to The First Hospital of Shanxi Medical University from January 2019 to September 2021,including demographic characteristics,drugs inducing liver injury,and clinical manifestations,and changes in liver function,treatment outcome,and adverse reactions were compared between the patients treated with glucocorticoid(glucocorticoid group) and those not treated with glucocorticoid(control group).The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups.Results A total of 88 patients with DILI were included in analysis,among whom there were 33 male patients and 55 female patients,with a median age of 49 years,and there were 61 patients in the control group and 27 patients in the glucocorticoid group.Hepatocellular injury type was the main clinical type,and traditional Chinese medicine and dietary supplements were the most common drugs inducing liver injury.Main clinical manifestations included jaundice,nausea,and poor appetite,and 6 patients(6/88,6.82%) progressed to grade 4 DILI,with 2 patients in the glucocorticoid group and 4 in the control group.The comparison of baseline characteristics showed that there were significant differences between the glucocorticoid group and the control group in aspartate aminotransferase,gamma-glutamyl transpeptidase(GGT),total bilirubin(TBil),and the proportion of patients with positive immune indices(all P<0.05).On day 3 of treatment,there were significant differences between the two groups in the reduction rates of TBil,international normalized ratio(INR),and total bile acid(TBA)(all P<0.05);on day 7 of treatment,there were significant differences between the two groups in the reduction rates of alanine aminotransferase,GGT,INR,and TBA(all P<0.05).Compared with the control group,the glucocorticoid group had a significantly higher cumulative response rate on days 3 and 7 of treatment(day 3:59.26% vs 29.51%,χ^(2)=55.82,P=0.008;day 7:81.48% vs 29.51%,χ^(2)=64.27,P<0.001).In the glucocorticoid group,the 2 patients with grade 4 DILI showed no response,while treatment response was observed in 93.75% of the patients who were treated with glucocorticoid due to the reduction in liver enzymes and the persistent increase(or a lack of significant reduction) in bilirubin after conventional liver-protecting treatment.Conclusion Traditional Chinese medicine and dietary supplements are the most common drugs inducing liver injury,and short-term use of glucocorticoids may bring benefits to the patients with grade 3 DILI who fail to achieve a satisfactory reduction in bilirubin after conventional treatment.