关键词: 药物性肝损伤, 白介素6, 肿瘤坏死因子-α, 白介素10, 肝损伤程度

Abstract: Objective To explore the levels of serum interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10) and their correlation with the severity of drug-induced liver injury(DILI). Methods Between June 2021 and June 2023, a total of 96 patients treated for DILI at our hospital were designated as the observation group. This group was stratified into 48 cases with mild liver injury, 37 with moderate liver injury, and 11 with severe liver injury based on the extent of liver function impairment. Additionally, 84 individuals with normal liver function, who underwent physical examinations at our hospital’s examination center during the same period, selected as the healthy control group. We conducted comparisons of serum IL-6, TNF-α and IL-10 levels between the DILI patients and the healthy group. The analysis also included comparisons of these cytokine levels among DILI patients with varing degrees of liver injury both before and after receiving symptomatic treatments, such as liver protection measures. Furthermore, the types of drugs responsible of liver injury in patients were compared across different severity levels. To determine the correlation between cytokine levels and the severity of liver injury, Spearman rank correlation analysis was utilized. This comprehensive approach allowed for a detailed examination of the relationship between inflammatory markers and liver injury severity in patients experiencing DILI. Results In the Observation group of 96 patients with DILI, levels of IL-6 and TNF-α were significantly higher compared to the healthy control group: IL-6 at [(29.8±6.4) pg/mL and TNF-α at (13.6±3.5) pg/mL) versus (12.4±3.7)pg/ml and (3.8±1.3) pg/mL, respectively, in the control group. Conversely, IL-10 levels were lower in the DILI group[(1.3±0.4) pg/mL] compared to the healthy group [(4.9±0.8) pg/mL ], with statistical significance(P<0.05). The analysis revealed no significant difference in the classes of drugs causing liver injury among patients with varying degrees of drug-induced liver injury (P>0.05). In severe liver injury, levels of IL-6 and TNF-α levels[(37.6±10.5) pg/mL, (23.1±5.6) pg/mL] were higher than those in moderate liver injury [(31.5±8.1) pg/mL, (15.9±3.4) pg/mL], and IL-10 levels were lower (1.1±0.3) pg/mL compared to moderate liver injury[(1.6±0.6) pg/mL]. In moderate liver injury, cytokine levels were also higher than those in the mild liver injury group, where IL-6, TNF-α levels were (26.6±3.7) pg/mL and (11.3±1.1) pg/mL, respectively, and IL-10 levels were (2.7±0.6) pg/mL. After treatment, the serum levels of IL-6 and TNF-α in the severe liver injury were still higher than those in the moderate liver injury grou, recorded at [(23.5±3.7) pg/mL and (8.9±3.6) pg/mL respectively. Compared to (19.4±3.5) pg/mLand (6.2±1.4) pg/mL in the moderate group. Additionally, IL-10 levels were lower in the severe injury group[ (2.9±0.9) pg/mL] compared to the moderate injury group [(3.7±0.8) pg/mL]. In the moderate liver injury group, IL-6 and TNF-α levels were higher than in the mild liver injury group, which showed levels of[(16.5±2.9) pg/mL, and (4.7±1.2) pg/mL, respectively. IL-10 levels were also lower in the moderate group compared to the mild group[ (4.2±1.1) pg/mL] (P<0.05). Correlation analysis indicated a positive correslation between the severity of liver damage and serum levels of IL-6 and TNF-α in patients with DILI. Conversely, IL-10 levels showed a negative correlation with the severity of liver injury(r=0.753, 0.814, -0.792, P<0.05). Conclusion The serum levels of IL-6, TNF-α,and IL-10 in patients with drug-induced liver injury(DILI) are closely associated with the degree of liver injury. These biomarkers can be used as clinical tools for assessing disease severity, evaluating treatment effects and predicting prognosis. Thus, they possess significant clinical and diagnostic value.

Key words: Drug-induced liver injury, Interleukin 6, Tumor necrosis factor-α, Interleukin 10, Degree of liver injury