乙型肝炎病毒相关慢加急性（亚急性）肝功能衰竭患者外周血单个核细胞中干扰素诱导蛋白-10的表达及其对预后的判断价值

Dynamic interferon-inducible protein-lO expressions in the peripheral blood mononuclear cells and its prognostic value in patients with hepatitis B virus related acute-on-chronic live failure

目的探讨HBV相关慢加急性（亚急性）肝功能衰竭（hepatitis B virus related acute-on-chronic live failure, HBV-ACLF）患者PBMC中干扰素诱导蛋白10（interferon-inducible protein-10，IP-10）的表达和终末期肝病模型（model for end-stage live disease，MELD）评分的动态变化对患者短期预后的判断价值。 方法选取2013年10月至2015年8月湖北文理学院附属医院收治的HBV-ACLF患者80例，随访3个月，死亡33例，存活47例。比较两组患者入院时、治疗1周、治疗2周的IP-10表达水平和MELD评分。应用受试者工作特征曲线下面积（area under curve，AUC）评估IP-10及MELD评分对预后的准确性，采用多元logistic回归分析、Kaplan-Meier生存曲线分析IP10表达和MELD评分对HBV-ACLF患者病死率的影响。 结果入院时、治疗1周、治疗2周时，未存活组患者的IP-10表达分别为1.095±0.202、1.071±0.181和1.078±0.198，存活组患者分别为0.894±0.181、0.770±0.153和0.732±0.137，两组比较差异有统计学意义（t值分别为4.66、8.02和9.27，均P〈0.01）。未存活组患者的MELD分别为26.70±5.50、27.39±6.24和28.64±6.44，存活组患者分别为23.89±4.41、21.57±4.68和18.87±3.92，两组比较差异有统计学意义（t值分别为2.53、4.77和8.42，均P〈0.01）。存活组患者入院时MELD评分和IP-10表达均明显高于治疗1周和2周时（F＝13.464、15.711，均P〈0.01）；而未存活组3个时间段比较，差异无统计学意义（F＝0.129、0.864，均P〉0.05）。治疗2周时IP-10的AUC为0.935，MELD的AUC为0.903（Z＝0.788，P＝0.045）；但治疗1周与2周时IP-10的AUC差异无统计学意义（0.935比0.909，Z＝0.640，P〉0.05）。且治疗1周时IP10和治疗2周时MELD的AUC差异无统计学意义（0.909比0.903，Z＝0.133，P〉0.05）。1周时IP-10≥0.902、2周时MELD〉22.5和2周时IP-10≥0.846是患者死亡的独立危险因素（OR值分别为11.29、6.60和15.27，95%CI分别为1.06～119.74、1.27～34.26、1.39～167.62，均P〈0.05）。 结论IP-10表达与MELD动态监测联合用于HBV-ACLF预后评估有更大的临床应用价值。

ObjectiveTo investigate the predictive value of dynamic changes of interferon-inducible protein-10 （IP-10） expression in the peripheral blood mononuclear cells and the model for end-stage 1iver disease （MELD） scores for short-term mortality in hepatitis B virus related acute-on-chronic liver failure （HBV-ACLF） patients. MethodsEighty patients with HBV-ACLF admitted to the Affiliated Hospital of Hubei College of Arts and Sciences from October 2013 to August 2015 were selected. During 3 months of follow-up, 33 patients died and 47 survived. The expression level of IP-10 and MELD score of two groups were measured at admission and week 1 and week 2 after treatment. The means between two groups were compared. Accuracy of predicting short-term mortality was performed by area under receiver operating characteristic curve （AUC）. Multivariate logistic regression analysis and Kaplan-Meier survival curve were used to analyze the effect of IP-10 expression and MELD score on the mortality of HBV-ACLF patients. ResultsThe expressions of IP-10 at admission and at week 1 and 2 after treatment in the death group were 1.095±0.202, 1.071±0.181, and 1.078±0.198, respectively, those in the survival group were 0.894±0.181, 0.770±0.153, and 0.732±0.137, respectively, which were significantly different （t=4.66, 8.02 and 9.27, respectively, all P〈0.01）. The MELD scores at admission and at week 1 and 2 after treatment in the death group were 26.70±5.50, 27.39±6.24, and 28.64±6.44, respectively, those in the survival group were 23.89±4.41, 21.57±4.68, and 18.87±3.92, respectively, which were significantly different （t=2.53, 4.77 and 8.42, respectively, all P〈0.01）. Analysis of variance showed that the MELD score and IP-10 expression in the survival group at admission were significantly higher than those at week 1 and week 2 after treatment （F=13.464 and 15.711, respectively, both P〈0.01）, while there were no significant differences in the death group （F=0.129 and 0.864, respectively, both P〉0.05）. The AUC of IP-10 at week 2 after treatment was 0.935, that of MELD score was 0.903 （Z=0.788, P=0.045）, while there was no significant difference of AUC between week 1 and week 2 （0.935 vs 0.909, Z=0.640, P〉0.05）. In addition, the AUC of IP-10 level at week 1 and MELD score at week 2 after treatment showed no significant difference （0.909 vs 0.903, Z=0.133, P〉0.05）. Logistic multivariate regression analysis showed that IP-10≥0.902 at week 1, MELD≥22.5 and IP-10≥0.846 at week 2 were independent risk factors for death （OR=11.29, 6.60, and 15.27, respectively; 95% CI=1.06-119.74, 1.27-34.26, and 1.39-167.62, respectively; all P〈0.05）. ConclusionThe dynamic monitor of both IP-10 levels and MELD scores may have greater value in predicting prognosis of patients with HBV-ACLF.