恩替卡韦联合复方鳖甲软肝片治疗慢性乙型肝炎的显著组织学应答影响因素分析及预测模型构建  

Determinants of significant histological response and nomogram construction for entecavir-Biejia Ruangan combination therapy in chronic hepatitis B

作　　者：徐然 何权威 常秀娟 陈艳 杨永平 XU Ran;HE Quanwei;CHANG Xiujuan;CHEN Yan;YANG Yongping(Department of Hepatology,the Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China Medical School of Chinese PLA,Beijing 100853,China)

机构地区：[1]解放军总医院第五医学中心肝病医学部,北京100039 [2]解放军医学院,北京100853 [3]解放军总医院海南医院消化内科,三亚572013

出　　处：《传染病信息》2025年第2期103-108,共6页Infectious Disease Information

基　　金：国家“十三五”科技重大专项(018ZX10725-506);首都临床特色诊疗技术研究及转化应用(Z221100007422002)。

摘　　要：目的本研究旨在探索慢性乙型肝炎(chronic hepatitis B,CHB)患者经恩替卡韦联合复方鳖甲软肝片(Biejia-Ruangan compound,BRC)治疗后获得显著组织学应答的影响因素,并建立列线图模型以无创评估治疗效果。方法研究对象为2013年10月至2014年10月期间,来自14家医院的500例CHB患者,经筛选后最终纳入369例。患者接受恩替卡韦联合BRC治疗72周,并根据治疗后是否获得显著组织学应答分为应答组与无应答组。收集基线及治疗后的临床和病理资料,并进行肝组织学检查和肝硬度测量。采用多因素Logistic回归分析筛选影响因素,并建立列线图模型,评估模型性能。结果应答组83例,无应答组286例。多因素Logistic回归分析显示患者基线时的年龄、肝硬度测量值(liver stiffness measurement,LSM),以及治疗72周后的LSM、丙氨酸氨基转移酶为影响显著组织学应答的独立因素。列线图模型预测准确性良好,校正曲线紧密贴合理想曲线,决策曲线优于天冬氨酸氨基转移酶和血小板比率指数、肝纤维化4指数及单独的LSM,受试者操作特征曲线下面积为0.83(95%置信区间:0.78~0.89)。结论本研究建立的列线图模型,为评估CHB患者恩替卡韦联合BRC治疗后的显著组织学应答提供了准确、无创的方法,具有临床应用价值和创新性。Objective This study aimed to investigate the factors influencing significant histological response in chronic hepatitis B(CHB)patients following treatment with entecavir combined with Biejia-Ruangan compound(BRC),and to develop a nomogram model for noninvasive evaluation of treatment efficacy.Methods A total of 500 CHB patients from 14 hospitals between October 2013 and October 2014 were included in the study,with 369 patients ultimately enrolled after screening.Patients received 72 weeks of treatment with entecavir plus BRC and were categorized into responder and non-responder groups based on the achievement of significant histological response post-treatment.Clinical and pathological data were collected at baseline and after treatment,including liver histological examination and liver stiffness measurement(LSM).Multivariate logistic regression analysis was conducted to identify influencing factors,and a nomogram model was established to assess the model's performance.ResultsThe responder group comprised 83 patients,while the non-responder group included 286 patients.Age,LSM at baseline,and LSM along with alanine aminotransferase(ALT)levels after 72 weeks of treatment were identified as independent factors influencing significant histological response.The nomogram model exhibited good predictive accuracy,with the calibration curve closely aligning with the ideal curve.Decision curve analysis(DCA)revealed superior performance compared to APRI,FIB-4,and LSM alone,with an area under the receiver operating characteristic curve(ROC)of 0.83(95%Cl:0.78~0.89).Conclusion The nomogram model developed in this study offers an accurate and noninvasive approach for assessing significant histological response in CHB patients treated with entecavir combined with BRC,demonstrating clinical applicability and innovation.

关 键 词：慢性乙型肝炎 恩替卡韦 复方鳖甲软肝片 显著组织学应答 列线图模型 

分 类 号：R512.62[医药卫生—内科学]