巨噬细胞及其细胞因子在HBV相关慢加急性肝衰竭患者短期预后中的临床价值分析

Analysis of clinical value of macrophages and its cytokines in short-term prognosis of patients with HBV associated acute-on-chronic liver failure

目的分析巨噬细胞(macrophage,Mφ)及其相关细胞因子在HBV相关慢加急性肝衰竭(HBV associated acute-on-chronic liver failure,HBV-ACLF)疾病预后中的有关变化,探讨Mφ极化状况对评估HBV-ACLF患者预后的临床价值。方法纳入107例于新疆医科大学第一附属医院确诊的HBV-ACLF患者开展前瞻性研究,收集患者的基线临床资料,并检测患者1型巨噬细胞(M1)和2型巨噬细胞(M2)水平,以及肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、转化生长因子β(TGF-β)和白介素10(IL-10)等相关细胞因子表达水平,根据患者的90 d生存情况,将研究对象分为存活组(n=42)和死亡组(n=65)。分析研究对象Mφ及其相关细胞因子与肝脏功能指标的相关性,采用Logistic回归分析独立相关因素,并绘制受试者工作特征曲线(receiver operator characteristic curve,ROC curve)来分析以上指标对HBV-ACLF患者预后的评判能力。结果死亡组患者的总胆红素(T-BIL)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)以及终末期肝病模型(model for end-stage liver disease,MELD)评分水平显著高于生存组患者(P<0.05)。MELD评分与M1、M1/M2、TNF-α、IL-6、TGF-β和IL-10呈正相关关系,与M2呈负相关关系。Logistic回归发现M2是HBV-ACLF患者预后的独立保护因素而MELD评分和TGF-β是独立危险因素。ROC curve显示,MELD评分联合M2或TGF-β可提高对HBV-ACLF患者预后的预测能力。结论本研究发现MELD评分、M2和TGF-β均是HBV-ACLF患者90 d预后的独立相关因素,且使用MELD评分联合M2或TGF-β可提高HBV-ACLF患者的临床早期预测效率,为患者开展及时有效的治疗提供理论资料。

ObjectiveTo analyze the level of macrophage(Mφ)and its related cytokines in the prognosis of HBV-associated acute-on-chronic liver failure(HBV-ACLF),and to evaluate the clinical value of Mφpolarization in evaluating the prognosis of HBV-ACLF patients.MethodsA prospective study was conducted in 107 patients with HBV-ACLF diagnosed at the hospital.Baseline clinical data were collected,and the levels of type 1 macrophages(M1),type 2 macrophages(M2),and tumor necrosis factor(TNF-α)、interleukin(IL-6),transforming growth factor(TGF-β)and interleukin(IL-10)were measured.According to the 90 day survival of the patients,the subjects were divided into survival group(n=42)and death group(n=65).The correlation between Mφand its related cytokines and liver function indexes were analyzed,and the independent related factors were analyzed by Logistic regression,the receiver operator characteristic curve(ROC curve)was drawn to analyze the prognostic value of the above indexes in patients with HBV-ACLF.ResultsThe levels of total bilirubin(T-BIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and model for end-stage liver disease(MELD)in the death group were significantly higher than those in the survival group(P<0.05).The MELD score was positively correlated with M1,M1/M2,TNF-α,IL-6,TGF-βand IL-10,and it negatively correlated with M2.Logistic regression analysis showed that M2 was an independent protective factor for the prognosis of the patients with HBV-ACLF,while MELD score and TGF-βwere independent risk factors.The ROC curve showed that MELD score combined with M2 and TGF-βincreased the predictive ability of prognosis in patients with HBV-ACLF.ConclusionMELD score,M2 and TGF-βare independent prognostic factors in patients with HBV-ACLF at 90 days,and MELD score combined with M2 or TGF-βcan improve the clinical early prediction efficiency of the patients with HBV-ACLF,and it provides theoretical data for timely and effective treatment of the patients.