实用医学杂志 ›› 2026, Vol. 42 ›› Issue (4): 571-578.doi: 10.3969/j.issn.1006-5725.2026.04.005

• 慢性病防治专栏 • 上一篇    

基线血清乙型肝炎病毒RNA水平对慢性乙型肝炎经核苷(酸)类似物治疗后乙型肝炎e抗原血清学转换的预测价值

吴月1,2,刘立1,吴磊1,钱昌珍1,2,赵智蓉1,李海雯1,杨永锐1()   

  1. 1.昆明市第三人民医院(云南省传染性疾病临床医学中心)肝病科 (云南 昆明 650000 )
    2.大理大学公共卫生学院 (云南 大理 671000 )
  • 收稿日期:2025-11-07 出版日期:2026-02-25 发布日期:2026-02-25
  • 通讯作者: 杨永锐 E-mail:595144613@qq.com
  • 基金资助:
    云南省科技厅创新引导与科技型企业培育计划项目(202504AM350026);昆明市卫生科技项目(2025-03-08-012)

Predictive value of baseline serum HBV RNA levels for HBeAg seroconversion after nucleos(t)ide analogues therapy in chronic hepatitis B

Yue WU1,2,Li LIU1,Lei WU1,Changzhen QIAN1,2,Zhirong ZHAO1,Haiwen LI1,Yongrui YANG1()   

  1. 1.Department of Hepatology,Kunming Third People's Hospital (Yunnan Provincial Clinical Medical Center for Infectious Diseases),Kunming 650000,Yunnan,China
    2.School of Public Health,Dali University,Dali 671000,Yunnan,China
  • Received:2025-11-07 Online:2026-02-25 Published:2026-02-25
  • Contact: Yongrui YANG E-mail:595144613@qq.com

摘要:

目的 评估基线血清乙型肝炎病毒(HBV)RNA水平对核苷(酸)类似物(NAs)治疗后慢性乙型肝炎(CHB)患者乙型肝炎e抗原(HBeAg)血清学转换的预测能力。 方法 纳入2023年7月至2024年9月在昆明市第三人民医院肝病科就诊并接受NAs治疗的317例HBeAg阳性CHB患者为研究对象,根据治疗48周时是否发生HBeAg血清学转换,将其分为转换组和未转换组,回顾性分析基线血清HBV RNA等相关指标水平。单因素分析有统计学意义的变量经多重共线性检验后,进行多因素logistic回归分析筛选独立影响因素。借助R软件“rms”程序包建立列线图风险预测模型,运用Bootstrap抽样法(B = 1 000)绘制模型校准曲线,采用Hosmer-Lemeshow检验评估模型的拟合度,同时绘制受试者工作特征(ROC)曲线并计算曲线下面积(AUC)。 结果 NAs治疗48周时,317例HBeAg阳性CHB患者中,23.97%(76/317)发生HBeAg血清学转换。基线HBV RNA(OR = 12.630,95%CI: 6.096 ~ 26.167,P < 0.001)、乙型肝炎病毒核心抗体(HBcAb)(OR = 0.110,95%CI: 0.041 ~ 0.298,P < 0.001)、甲胎蛋白(AFP)(OR = 1.231,95%CI: 1.072 ~ 1.413,P = 0.003)、谷氨酰转移酶(GGT)(OR = 1.010,95%CI: 1.001 ~ 1.019,P = 0.034)是HBeAg发生血清学转换的独立预测因子,据此建立列线图预测模型,Bootstrap(B = 1 000)抽样法绘制模型校准曲线,预测概率与实际观测概率高度吻合,Hosmer-Lemeshow拟合优度检验结果(χ2= 4.939,P = 0.764)进一步证明模型具有良好的校准度。联合预测因子AUC:0.894,95%CI: 0.855 ~ 0.932,其中HBV RNA AUC:0.786,95%CI: 0.718 ~ 0.855,灵敏度为0.913,特异度为0.645。 结论 基线血清HBV RNA水平对NAs治疗CHB患者HBeAg血清学转换具有一定的预测价值。

关键词: 血清乙型肝炎病毒 RNA, 慢性乙型肝炎, 核苷(酸)类似物, 乙型肝炎e抗原, 血清学转换

Abstract:

Objective To evaluate the predictive capacity of the baseline serum HBV RNA level for HBeAg seroconversion in patients with chronic hepatitis B (CHB) undergoing nucleos(t)ide analogues (NAs) treatment. Methods A total of 317 HBeAg-positive CHB patients who received nucleos(t)ide analogs (NAs) treatment in the Department of Hepatology, Kunming Third People's Hospital from July 2023 to September 2024 were recruited as the study subjects. These patients were categorized into the seroconversion group and the non-seroconversion group according to the occurrence of HBeAg seroconversion at week 48 of treatment. A retrospective analysis was carried out on the baseline serum HBV RNA levels and other relevant indicators. Variables that showed statistical significance in the univariate analysis were subjected to a multicollinearity test, followed by a multivariate Logistic regression analysis to identify the independent influencing factors for HBeAg seroconversion. The "rms" package in R software was utilized to construct a nomogram risk prediction model. Bootstrap sampling (B = 1 000) was applied to generate the calibration curve of the model. The Hosmer - Lemeshow test was adopted to assess the model's goodness-of-fit, and the receiver operating characteristic (ROC) curve was plotted with the calculation of the area under the curve (AUC). Results At the 48th week of NA treatment, 23.97% (76/317) of the 317 HBeAg-positive CHB patients achieved HBeAg seroconversion. Baseline HBV RNA (odds ratio [OR] = 12.630, 95% confidence interval [CI]: 6.096 ~ 26.167, P < 0.001), HBcAb (OR = 0.110, 95% CI: 0.041 ~ 0.298, P < 0.001), AFP (OR = 1.231, 95% CI: 1.072 ~ 1.413, P = 0.003), and GGT (OR = 1.010, 95% CI: 1.001 ~ 1.019, P = 0.034) were identified as independent predictors of HBeAg seroconversion. A nomogram prediction model was developed based on these factors. The calibration curve generated through Bootstrap sampling (B = 1 000) demonstrated a high level of consistency between the predicted probability and the actual observed probability of HBeAg seroconversion. The Hosmer-Lemeshow goodness-of-fit test (χ2 = 4.939, P = 0.764) further verified that the model had good calibration. The area under the curve (AUC) of the combined predictors was 0.894. Among them, the AUC of HBV RNA was 0.786, with a sensitivity of 0.913 and a specificity of 0.645. Conclusion The baseline serum HBV RNA level holds a specific predictive value for HBeAg seroconversion in chronic hepatitis B (CHB) patients undergoing nucleoside analogues (NAs) treatment.

Key words: serum HBV RNA, chronic hepatitis B, nucleos(t)ide analogues, HBeAg, seroconversion

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