Tu Can, Niu Ming, Wei Ai-Wu, Tang Jin-Fa, Zhang Le, Jing Jing, Xiao Xiao-He, Wang Jia-Bo
Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China.
China Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People's Republic of China.
J Inflamm Res. 2021 Mar 4;14:645-655. doi: 10.2147/JIR.S299892. eCollection 2021.
Drug-induced liver injury is a common adverse effect in clinical practice, with severe cases resulting in liver failure and even death. Identification and prediction of individuals susceptible to idiosyncratic DILI continues to remain a challenge.
In this study, we report that cytokines in human serum can be used to identify and predict individuals susceptible to -induced DILI (PM-DILI) in retrospective and prospective cohort studies.
In the retrospective pilot study, we compared serum cytokine expression profiles of the PM-DILI group (n=10) and the PM-Tolerant group (n=12) and found 10 cytokines with significant differences. In the replication cohort study, differences in the 10 cytokines between PM-DILI (n =11) and PM-Tolerant (n=13) groups were verified. Among them, 6 cytokines showed no significant differences at two time points, including liver injury and recovery stage of PM-DILI, suggesting that these 6 cytokines have no correlation with PM-DILI, however, they may be related to susceptibility. Furthermore, all the retrospective cohorts were combined, and a PM-DILI susceptibility prediction model was built by screening the 6 cytokines. The combination of (TNF-α and CCL-2) or VEGF showed the highest sensitivity and specificity. Finally, the efficacy of the above 3 cytokine combination models in predicting PM-DILI-susceptible individuals was verified before PM exposure in another independent prospective cohort (n=24), with sensitivity and specificity of 66.7% and 83.3%, respectively.
This proof-of-concept study demonstrates that the serum cytokine combination reflecting dysimmunity could be used as a new method to predict PM-DILI, thus providing a new perspective for improving the clinical management of IDILI.
药物性肝损伤是临床实践中常见的不良反应，严重病例可导致肝衰竭甚至死亡。识别和预测易患特异质性药物性肝损伤的个体仍然是一项挑战。
在本研究中，我们报告了在回顾性和前瞻性队列研究中，人血清中的细胞因子可用于识别和预测易患颗粒物诱导的药物性肝损伤（PM-DILI）的个体。
在回顾性试点研究中，我们比较了PM-DILI组（n=10）和PM耐受组（n=12）的血清细胞因子表达谱，发现10种细胞因子存在显著差异。在重复队列研究中，验证了PM-DILI组（n =11）和PM耐受组（n=13）之间这10种细胞因子的差异。其中，6种细胞因子在两个时间点无显著差异，包括PM-DILI的肝损伤和恢复阶段，这表明这6种细胞因子与PM-DILI无关，然而，它们可能与易感性有关。此外，将所有回顾性队列合并，通过筛选这6种细胞因子建立了PM-DILI易感性预测模型。（TNF-α和CCL-2）或VEGF的组合显示出最高的敏感性和特异性。最后，在另一个独立的前瞻性队列（n=24）中，在接触颗粒物之前验证了上述3种细胞因子组合模型在预测PM-DILI易感个体方面的有效性，敏感性和特异性分别为66.7%和83.3%。
这项概念验证研究表明，反映免疫失调的血清细胞因子组合可作为预测PM-DILI的新方法，从而为改善特异质性药物性肝损伤的临床管理提供新的视角。
