The Journal of Practical Medicine >

2026 , Vol. 42 >Issue 4: 571 - 578

DOI: https://doi.org/10.3969/j.issn.1006-5725.2026.04.005

Chronic Disease Control

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

  • Yue WU ,
  • Li LIU ,
  • Lei WU ,
  • Changzhen QIAN ,
  • Zhirong ZHAO ,
  • Haiwen LI ,
  • Yongrui YANG
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  • 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 date: 2025-11-07

  Online published: 2026-02-25

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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

Cite this article

Yue WU , Li LIU , Lei WU , Changzhen QIAN , Zhirong ZHAO , Haiwen LI , Yongrui YANG . Predictive value of baseline serum HBV RNA levels for HBeAg seroconversion after nucleos(t)ide analogues therapy in chronic hepatitis B[J]. The Journal of Practical Medicine, 2026 , 42(4) : 571 -578 . DOI: 10.3969/j.issn.1006-5725.2026.04.005

References

[1] 陈娅， 罗晓永， 陈应华， 等. HBV RNA预测乙型肝炎病毒相关肝细胞癌发病的价值［J］. 实用医学杂志， 2025， 41（21）： 3435-3441. doi：10.3969/j.issn.1006-5725.2025.21.020 .
[2] RAZAVI-SHEARER D， GAMKRELIDZE I， PAN C， et al. Global prevalence， cascade of care， and prophylaxis coverage of hepatitis B in 2022： A modelling study［J］. Lancet Gastroenterol Hepatol， 2023， 8（10）： 879-907. doi：10.1016/S2468-1253（23）00197-8 .
[3] XIA Y， GUO H. Hepatitis B virus cccDNA： Formation， regulation and therapeutic potential［J］. Antiviral Res， 2020， 180： 104824. doi：10.1016/j.antiviral.2020.104824 .
[4] KAO J H， HU T H， JIA J， et al. East Asia expert opinion on treatment initiation for chronic hepatitis B［J］. Aliment Pharmacol Ther， 2020， 52（10）： 1540-1550. doi：10.1111/apt.16097 .
[5] 中华医学会肝病学分会， 中华医学会感染病学分会. 慢性乙型肝炎防治指南（2022年版）［J］. 实用肝脏病杂志， 2023， 26（3）： 后插1-后插22. doi：10.3969/j.issn.1672-5069. 2023. 03.040 .
[6] 陈娟， 黄爱龙. 从HBV cccDNA角度谈乙型肝炎的功能性治愈［J］. 临床肝胆病杂志， 2022， 38（8）： 1716-1720. doi：10.3969/j.issn.1001-5256.2022.08.003 .
[7] XU W， LUO Q， ZHANG Y， et al. A case report： CccDNA and pgRNA remain positive in liver tissue in a chronic hepatitis B patient with functional cure［J］. Front Med， 2024， 11： 1427043. doi：10.3389/fmed.2024.1427043 .
[8] 蒋贝， 刘畅， 苏瑞， 等. 血清HBV RNA在HBeAg阴性慢性乙型肝炎患者中的检测价值［J］. 中华肝脏病杂志， 2019， 27（9）： 668-672. doi：10.3760/cma.j.issn.1007-3418.2019.09.002 .
[9] CORNBERG M， LOK A S， TERRAULT N A， et al. Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference（?）［J］. J Hepatol， 2020， 72（3）： 539-557. doi：10.1016/j.jhep.2019.11.003 .
[10] 中华医学会感染病学分会， 中华医学会肝病学分会， Chinese Medical Association. 慢性乙型肝炎临床治愈（功能性治愈）专家共识［J］. 临床肝胆病杂志， 2019， 35（8）： 1693-1701. doi：10.3969/j.issn.1001-5256.2019.08.008 .
[11] LU F， WANG J， CHEN X， et al. Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos（t）ide analogs［J］. Front Med， 2017， 11（4）： 502-508. doi：10.1007/s11684-017-0590-z .
[12] 顾子杨， 王安辉， 何文昌， 等. 慢性乙型肝炎患者HBeAg血清学转换影响因素的研究进展［J］. 临床肝胆病杂志， 2022， 38（11）： 2581-2585. doi：10.3969/j.issn.1001-5256.2022.11.029 .
[13] 吕高燕， 王春娟. 血清HBeAg阳性慢性乙型肝炎患者接受核苷（酸）类似物治疗疗效和检测血清HBV RNA的意义［J］. 肝脏， 2024， 29（1）： 77-80. doi：10.3969/j.issn.1008-1704. 2024. 01.023 .
[14] THOMPSON A J， JACKSON K， BONANZINGA S， et al. Baseline serum HBV RNA is associated with the risk of hepatitis flare after stopping nucleoside analog therapy in HBeAg-negative participants［J］. Hepatol Commun， 2023， 7（8）： e0188. doi：10.1097/HC9.0000000000000188 .
[15] PAPATHEODORIDI M， PAPACHRISTOU E， MOSCHIDIS Z， et al. Significance of serum HBV RNA in non-cirrhotic HBeAg-negative chronic hepatitis B patients who discontinue effective antiviral therapy［J］. J Viral Hepat， 2022， 29（11）： 948-957. doi：10.1111/jvh.13729 .
[16] LARAS A， PAPATHEODORIDI M， PANOPOULOU E， et al. Serum hepatitis B virus RNA detectability， composition and clinical significance in patients with ab initio hepatitis B e antigen negative chronic hepatitis B［J］. Virol J， 2022， 19（1）： 22. doi：10.1186/s12985-022-01749-7 .
[17] CAREY I， GERSCH J， WANG B， et al. Pregenomic HBV RNA and hepatitis B core-related antigen predict outcomes in hepatitis B e antigen-negative chronic hepatitis B patients suppressed on nucleos（T）ide analogue therapy［J］. Hepatology， 2020， 72（1）： 42-57. doi：10.1002/hep.31026 .
[18] CHOI W M， YIP T C， KIM W R， et al. Chronic hepatitis B baseline viral load and on-treatment liver cancer risk： A multinational cohort study of HBeAg-positive patients［J］. Hepatology， 2024， 80（2）： 428-439. doi：10.1097/HEP.0000000000000752 .
[19] CHEN Y， WANG G， LI M， et al. Virological and immunological characteristics of HBeAg-positive chronic hepatitis B patients with low HBsAg levels［J］. Aliment Pharmacol Ther， 2025， 61（5）： 814-823. doi：10.1111/apt.18448 .
[20] MOHAREB A M， LIU A F， KIM A Y， et al. Clearance of hepatitis B e antigen in untreated chronic hepatitis B virus infection： A systematic review and meta-analysis［J］. J Infect Dis， 2022， 226（10）： 1761-1770. doi：10.1093/infdis/jiac168 .
[21] CHAN H L Y， FUNG S， SETO W K， et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection： A randomised， double-blind， phase 3， non-inferiority trial［J］. Lancet Gastroenterol Hepatol， 2016， 1（3）： 185-195. doi：10.1016/S2468-1253（16）30024-3 .
[22] GU Z， JIANG Q， ABULAITI A， et al. Hepatitis B virus enhancer 1 activates preS1 and preS2 promoters of integrated HBV DNA impairing HBsAg secretion［J］. JHEP Rep， 2024， 6（9）： 101144. doi：10.1016/j.jhepr.2024.101144 .
[23] LIAO H， LIU Y， LI X， et al. Monitoring of serum HBV RNA， HBcrAg， HBsAg and anti-HBc levels in patients during long-term nucleoside/nucleotide analogue therapy［J］. Antivir Ther， 2019， 24（2）： 105-115. doi：10.3851/IMP3280 .
[24] WANG J， SHEN T， HUANG X， et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound［J］. J Hepatol， 2016， 65（4）： 700-710. doi：10.1016/j.jhep.2016.05.029 .
[25] ZHANG M， LI G， SHANG J， et al. Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients： A longitudinal cohort study［J］. Hepatol Int， 2020， 14（2）： 212-224. doi：10.1007/s12072-020-10015-3 .
[26] VAN B?MMEL F， VAN B?MMEL A， KRAUEL A， et al. Serum HBV RNA as a predictor of peginterferon Alfa-2a response in patients with HBeAg-positive chronic hepatitis B［J］. J Infect Dis， 2018， 218（7）： 1066-1074. doi：10.1093/infdis/jiy270 .
[27] VAN CAMPENHOUT M J H， VAN B?MMEL F， PFEFFERKORN M， et al. Serum hepatitis B virus RNA predicts response to peginterferon treatment in HBeAg-positive chronic hepatitis B［J］. J Viral Hepat， 2020， 27（6）： 610-619. doi：10.1111/jvh. 13272 .
[28] WANG Y， LIAO H， DENG Z， et al. Serum HBV RNA predicts HBeAg clearance and seroconversion in patients with chronic hepatitis B treated with nucleos（t）ide analogues［J］. J Viral Hepat， 2022， 29（6）： 420-431. doi：10.1111/jvh.13671 .
[29] 朱莹， 罗园香， 郭凤霞， 等. 血清HBV RNA预测恩替卡韦治疗慢性乙型肝炎患者疗效的价值［J］. 南方医科大学学报， 2022， 42（8）： 1250-1255. doi：10.12122/j.issn.1673-4254. 2022. 08.19 .
[30] BRAKENHOFF S M， DE KNEGT R J， OLIVEIRA J， et al. Levels of antibodies to hepatitis B core antigen are associated with liver inflammation and response to peginterferon in patients with chronic hepatitis B［J］. J Infect Dis， 2022， 227（1）： 113-122. doi：10.1093/infdis/jiac210 .
[31] YANG H C， TSOU H H， PEI S N， et al. Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection［J］. J Hepatol， 2018， 69（2）： 286-292. doi：10.1016/j.jhep.2018.02.033 .
[32] SHI Y， WANG Z， GE S， et al. Hepatitis B core antibody level： A surrogate marker for host antiviral immunity in chronic hepatitis B virus infections［J］. Viruses， 2023， 15（5）： 1111. doi：10.3390/v15051111 .
[33] SUN L， GU M， CAI J， et al. Combining γ-GT， PIVKA-II， and AFP to predict long-term prognosis in patients with hepatocellular carcinoma after hepatectomy［J］. Clin Exp Pharmacol Physiol， 2023， 50（4）： 287-297. doi：10.1111/1440-1681.13745 .
[34] 卢英， 雍景超， 刘洋， 等. 血清甲胎蛋白、γ-谷氨酰转肽酶对肝细胞癌发生微血管侵犯的临床应用价值［J］. 南京医科大学学报（自然科学版）， 2023， 43（3）： 357-364. doi：10.7655/NYDXBNS20230309 .
[35] 邓兰. CHB患者血清HBeAg水平与肝脏炎症活动度及纤维化分级的关系研究［J］. 实用临床医药杂志， 2016， 20（17）： 63-66. doi：10.7619/jcmp.201617020 .
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