血清胆红素指标异常与药物性肝损主要临床特征的关系

The Associations between Abnormal Serum Bilirubin Levels and Clinical Characteristics of Drug-Induced Liver Damage

摘要: 目的：分析血清胆红素指标异常与药物性肝损(Drug-induced liver injury, DILI)主要临床特征的关系。方法：收集自2013年3月至2019年3月期间在青岛大学医学院附属医院住院治疗的142例DILI患者为研究对象，按照血清胆红素水平分为胆红素正常组和胆红素异常组，比较病因、肝功能生化指标、病程恢复特点以及糖皮质激素(Glucocorticoid, GC)治疗选择倾向。结果：与血清胆红素指标正常的DILI患者相比，胆红素水平升高的DILI患者入院时血清肝功能生化指标基线水平较高，除γ-谷氨酰转肽酶(γ-glutamine transpeptidase, γ-GT)之外，差异有统计学意义(P < 0.05)；住院治疗1周后谷草转氨酶(Aspartate aminotransferase, AST)下降速率较慢，总胆红素(Total bilirubin, TB)、间接胆红素(Indirect bilirubin, IB)及直接胆红素(Direct bilirubin, DB)下降速率较快，差异有统计学意义(P < 0.05)。患者住院天数以及肝功能生化指标完全恢复的患者例数差异有统计学意义(P < 0.05)。另外，血清胆红素水平升高的DILI患者治疗方案中应用GC的病例数较多；该组中应用GC的患者其血清肝酶基线水平明显高于未应用GC的患者，差异有统计学意义(P < 0.05)；治疗1周后肝酶下降速率较快，差异有统计学意义(P < 0.05)。结论：血清胆红素水平升高的DILI患者肝功能生化指标基线水平较高，治疗后AST恢复较慢，患者住院病程更长，治疗上更倾向于应用GC；在血清胆红素水平升高的DILI患者中，应用GC的患者血清肝酶基线水平较高，治疗后肝酶水平下降更显著。

Abstract: Objective: To analyze the associations between abnormal serum bilirubin levels and the clinical features of drug-induced liver injury (DILI). Methods: The clinical data of 142 DILI patients who were hospitalized in the Affiliated Hospital of Qingdao University Medical College were analyzed. According to the serum bilirubin levels, they were divided into normal bilirubin group and abnormal bilirubin group. The etiology, biochemical indicators of liver function, the characteristics of recovery, and selection of glucocorticoid (GC) treatment were compared. Results: Compared with DILI patients with normal serum bilirubin indexes, DILI patients with elevated bilirubin levels had a higher baseline level of serum biochemical indexes of liver function. The difference was statistically significant (P < 0.05), except for γ-glutamine transpeptidase (γ-GT). After a week of treatment, serum aspartate aminotransferase (AST) levels declined at a slower speed, while the levels of total bilirubin (TB), indirect bilirubin (IB) and direct bilirubin (DB) declined at a faster speed. The differences were statistically significant (P < 0.05). The differences in the length of stay and number of patients with full recovery of biochemical indicators of liver function were also statistically significant (P < 0.05). Moreover, in the group of DILI patients with elevated serum bilirubin levels more subjects adopted GC treatment. In this group, the baseline levels of serum liver enzymes of patients who applied GC were significantly higher than those of patients who did not apply GC. The differences were statistically significant (P < 0.05). After a week of treatment, the levels of liver enzymes in patients of this group decreased more rapidly. The differences were statistically significant (P < 0.05). Conclusion: DILI patients with elevated serum bilirubin levels have a higher baseline level of biochemical indicators of liver function, a slower recovery of AST after treatment, and a longer hospital stay. Moreover, GC was more frequently used in treatment regimen. Among DILI patients with elevated serum bilirubin levels, patients who applied GC have higher baseline levels of serum liver enzymes, and a more significant decrease in liver enzyme levels after treatment.