Table_3_Serum cytokine and chemokine profiles and disease prognosis in hepatitis B virus-related acute-on-chronic liver failure.docx

BackgroundHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) has significant morbidity and mortality and is associated with the induction of cytokines/chemokines, which might contribute to the pathogenesis of liver injury. This study aimed to explore the cytokine/chemokine profiles of patients with HBV-ACLF and develop a composite clinical prognostic model.
MethodsWe prospectively collected blood samples and the clinical data of 107 patients with HBV-ACLF admitted to the Beijing Ditan Hospital. The concentrations of 40-plex cytokines/chemokines were measured in 86 survivors and 21 non-survivors using the Luminex assay. Discrimination between the cytokine/chemokine profiles in different prognosis groups was analyzed using the multivariate statistical techniques of principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). An immune-clinical prognostic model was obtained using multivariate logistic regression analysis.
ResultsThe PCA and PLS-DA indicated that cytokine/chemokine profiling could clearly distinguish patients with different prognoses. A total of 14 cytokines, namely, IL-1β, IL-6, IL-8, IL-10, TNF-α, IFN-γ, CXCL1, CXCL2, CXCL9, CXCL13, CX3CL1, GM-SCF, CCL21, and CCL23, were significantly correlated with disease prognosis. Multivariate analysis identified CXCL2, IL-8, total bilirubin, and age as independent risk factors that constituted the immune-clinical prognostic model, which showed the strongest predictive value of 0.938 compared with those of the Chronic Liver Failure Consortium (CLIF-C) ACLF (0.785), Model for End-Stage Liver Disease (MELD) (0.669), and MELD-Na (0.723) scores (p < 0.05 for all).
ConclusionThe serum cytokine/chemokine profiles correlated with the 90-day prognosis of patients with HBV-ACLF. The proposed composite immune-clinical prognostic model resulted in more accurate prognostic estimates than those of the CLIF-C ACLF, MELD, and MELD-Na scores.

背景
乙型肝炎病毒相关慢加急性肝衰竭（hepatitis B virus-related acute-on-chronic liver failure, HBV-ACLF）具有较高的发病率与死亡率，其发生与细胞因子/趋化因子的诱导密切相关，而后者可能参与肝损伤的发病过程。本研究旨在探讨HBV-ACLF患者的细胞因子/趋化因子谱，并构建综合临床预后模型。

方法
本研究前瞻性收集了北京地坛医院收治的107例HBV-ACLF患者的血液样本与临床资料。采用Luminex检测技术对86例存活患者与21例非存活患者的40联细胞因子/趋化因子浓度进行测定。通过主成分分析（principal component analysis, PCA）与偏最小二乘判别分析（partial least squares discriminant analysis, PLS-DA）等多元统计方法，分析不同预后组间的细胞因子/趋化因子谱差异。采用多因素logistic回归分析构建免疫-临床预后模型。

结果
主成分分析与偏最小二乘判别分析结果显示，细胞因子/趋化因子谱可清晰区分不同预后的HBV-ACLF患者。共有14种细胞因子与疾病预后显著相关，分别为IL-1β、IL-6、IL-8、IL-10、TNF-α、IFN-γ、CXCL1、CXCL2、CXCL9、CXCL13、CX3CL1、GM-SCF、CCL21及CCL23。多因素分析显示，CXCL2、IL-8、总胆红素及年龄为独立危险因素，以此构建的免疫-临床预后模型的预测价值最高（0.938），优于慢性肝衰竭联盟慢加急性肝衰竭预后评分（Chronic Liver Failure Consortium ACLF, CLIF-C ACLF，0.785）、终末期肝病模型（Model for End-Stage Liver Disease, MELD，0.669）及MELD-Na评分（0.723，所有比较P<0.05）。

结论
血清细胞因子/趋化因子谱与HBV-ACLF患者的90天预后密切相关。本研究构建的综合免疫-临床预后模型，其预后评估准确性优于CLIF-C ACLF、MELD及MELD-Na评分。