[Clinical study of serum human-βeta-defensin-1 level for evaluating short-term prognosis in patients with acute-on-chronic liver failure].

Objective: To evaluate the diagnostic value of serum human-βeta-defensin-1 level (HBD-1) for short-term (28-day) prognosis in patients with acute-on-chronic liver failure (ACLF). Methods: Fifty cases diagnosed with ACLF were selected. 20 cases with decompensated cirrhosis and 20 cases with compensated cirrhosis who were admitted at the same time were included. Age, gender, serum HBD-1 level, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte ratio (NLR), blood routine, coagulation function, liver function, kidney function, and other indicators from the three groups of patients were collected. Patients with ACLF were screened for indicators related to the short-term (28-day) prognosis. Patients were divided into an improvement group and a worsening group according to the 28-day disease outcome. The serum HBD-1 level and other above-mentioned indicators were compared between the two patient groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum HBD-1 levels for short-term prognosis in patients with ACLF. PCT, NLR, and prothrombin activity (PTA) application as a mono indicator and HBD-1 in combination with NLR, PCT, and PTA were compared to evaluate diagnostic efficacy for short-term prognosis in patients with ACLF. The intergroup mean of measurement data was determined using a t-test or analysis of variance. χ (2) test was used for comparison of count data. Spearman's rank correlation analysis was used for correlation analysis. Results: There was no statistically significant difference in age and gender among the three groups: ACLF, decompensated cirrhosis, and compensated cirrhosis (P > 0.05). The expression levels of serum HBD-1 in the ACLF group, decompensated cirrhosis group, and compensated cirrhosis group were (319.1 ± 44.4) ng/ml, (264.5 ± 46.5) ng/ml and (240.1 ± 35.4) ng/ml, respectively, while the ACLF group expression levels were significantly increased, with statistical significance (P < 0.01).The serum HBD-1 level was significantly higher in the ACLF worsening group (346.2 ± 43.6) ng/ml than that in the improvement group (308.5 ± 40.6) ng/ml, and the difference was statistically significant (P < 0.05). Correlation analysis showed that HBD-1, NLR, PCT, prothrombin time (PT), and international standardized ratio (INR) were negatively correlated with the 28-day disease outcome (improvement) of patients (P < 0.05). PTA was positively correlated with 28-day disease outcome (improvement) (P < 0.05). The area under the receiver operating characteristic curve (AUC) for evaluating HBD-1's diagnostic efficacy for short-term prognosis in patients with ACLF was 0.774, with a sensitivity of 0.750, a specificity of 0.786, and a cut-off point of 337.96 ng/ml. PCT, NLR, and PTA had greater diagnostic efficacy. HBD-1 combined with PTA had the highest diagnostic efficacy, with an AUC of 0.802, a sensitivity of 0.778, and a specificity of 0.786. The diagnostic efficacy of HBD-1+PCT, HBD-1+NLR and HBD-1, PCT, and NCR was superior to PTA mono. Conclusion: The serum HBD-1 level gradually increases with the aggravation of liver function injury and is negatively correlated with the short-term prognosis in patients with ACLF. Serum HBD-1 level has high sensitivity and specificity in predicting short-term prognosis in patients with ACLF, and its diagnostic efficacy is superior to that of PCT, NLR, and PTA. The combined application of HBD-1 and PTA has higher diagnostic efficacy; however, when the serum HBD-1 level is greater than 337.96ng/ml, it indicates poor prognosis in patients.目的： 评估血清人β防御素-1（HBD-1）水平对慢加急性肝衰竭（ACLF）患者短期（28 d）预后的诊断价值。 方法： 选择诊断为ACLF的患者50例，同时纳入同期住院的失代偿期肝硬化、代偿期肝硬化患者各20例，收集3组患者的年龄、性别、血清HBD-1水平、C反应蛋白（CRP）、降钙素原（PCT）、中性粒细胞计数/淋巴细胞计数（NLR）与血常规、凝血功能、肝功能、肾功能等指标，筛选与ACLF患者短期（28 d）预后相关的指标。依据患者28 d疾病转归情况分为好转组与恶化组，比较2组患者的血清HBD-1水平及上述其他指标。采用受试者操作特征（ROC）曲线分析血清HBD-1水平对ACLF患者短期预后的诊断效能，并与PCT、NLR、凝血酶原活动度（PTA）的诊断效能进行比较；将HBD-1分别与NLR、PCT、PTA联合，评估其对ACLF患者短期预后的诊断效能，并与单个指标应用时的诊断效能进行比较。计量资料组间均数比较采用t检验或方差分析，计数资料比较采用χ(2)检验；相关分析采用Spearman秩相关分析。 结果： ACLF组、失代偿期肝硬化组、代偿期肝硬化组3组患者的年龄、性别之间的差异无统计学意义（P值均> 0.05）。血清HBD-1水平在ACLF组、失代偿期肝硬化组、代偿期肝硬化组3组患者中的表达水平分别为（319.1±44.4）ng/ml、（264.5±46.5）ng/ml、（240.1±35.4）ng/ml，其在ACLF组患者中的表达水平明显增高，差异有统计学意义（P < 0.01）。ACLF恶化组患者的血清HBD-1水平为（346.2±43.6）ng/ml，明显高于好转组的（308.5±40.6）ng/ml，差异有统计学意义（P < 0.05）。相关性分析提示HBD-1、NLR、PCT、凝血酶原时间（PT）、国际标准化比值（INR）与患者28 d疾病转归（好转）呈负相关（P值均< 0.05）；PTA与患者28 d疾病转归（好转）呈正相关（P < 0.05）。ROC曲线评估HBD-1对ACLF患者短期预后的诊断效能的曲线下面积（AUC）为0.774、灵敏度为0.750、特异度为0.786、截断值为337.96 ng/ml，诊断效能高于PCT、NLR、PTA；HBD-1联合PTA的诊断效能最高，AUC为0.802、灵敏度为0.778、特异度为0.786，优于HBD-1+PCT、HBD-1+NLR及HBD-1、PCT、NLR、PTA单独应用的诊断效能。 结论： 血清HBD-1水平随肝脏功能受损程度的加重而逐渐增加，与ACLF患者的短期预后呈负相关；血清HBD-1水平预测ACLF患者短期预后的灵敏度与特异度高，其诊断效能优于PCT、NLR、PTA，HBD-1与PTA联用，诊断效能更高；当血清HBD-1水平高于337.96 ng/ml时，提示患者预后不佳。.