医学检查与临床诊断

HBV RNA预测乙型肝炎病毒相关肝细胞癌发病的价值

  • 陈娅 ,
  • 罗晓永 ,
  • 陈应华 ,
  • 罗亚文
展开
  • 遵义医科大学附属医院感染科 (贵州 遵义 563000 )

收稿日期: 2025-06-28

  网络出版日期: 2025-11-13

基金资助

贵州省卫生健康委科学技术基金项目(gzwkj2021-071)

Expression of HBV RNA in hepatitis B virus⁃associated hepatocellular carcinoma

  • Ya CHEN ,
  • Xiaoyong LUO ,
  • Yinghua CHEN ,
  • Yawen. LUO
Expand
  • Department of Infectious Diseases,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou,China

Received date: 2025-06-28

  Online published: 2025-11-13

摘要

目的 探讨HBV RNA在乙型肝炎病毒相关肝细胞癌中的表达。 方法 收集2023年12月至2025年1月在遵义医科大学附属医院门诊或住院部就诊的259例CHB患者和41例乙型肝炎病毒相关肝细胞癌(HBV-HCC)患者为研究对象,比较两组间年龄、性别、HBV RNA、HBV DNA、ALT、AST及TBIL指标有无差异,比较同组间HBV RNA与HBV DNA病毒载量有无差异,分析同组间HBV RNA与HBV DNA、ALT、AST及TBIL的相关性,通过ROC曲线得出HBV RNA对HBV-HCC的诊断效能。 结果 HBV-HCC组患者的HBV RNA载量、HBV RNA阳性率、ALT、AST、TBIL水平、年龄及男性患者占比均高于CHB组(P < 0.05);绘制散点图发现CHB组患者的HBV DNA载量高于HBV RNA载量(P < 0.000 1);相关性分析显示两组患者的HBV RNA与HBV DNA 均呈正相关(P < 0.05),CHB组患者的HBV RNA与ALT、AST及TBIL呈正相关(P < 0.001);ROC曲线结果显示,HBV RNA的曲线下面积(AUC)为0.692 3(P < 0.000 1),HBV RNA诊断HBV-HCC的最佳截断值为 ≥ 2.5 log10copies/mL。 结论 血清HBV RNA水平对识别HBV-HCC具有较高的敏感性和特异性,可作为预测HBV-HCC发生的可靠指标。

本文引用格式

陈娅 , 罗晓永 , 陈应华 , 罗亚文 . 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

Abstract

Objective To investigate the expression of HBV RNA in hepatitis B virus?associated hepatocellular carcinoma (HBV?HCC). Methods A total of 259 patients with chronic hepatitis B (CHB) and 41 HBV?HCC patients treated in the outpatient or inpatient department of the Affiliated Hospital of Zunyi Medical University from December 2023 to January 2025 were enrolled as subjects. The differences in age, sex, and levels of HBV RNA, HBV DNA, ALT, AST, and TBIL between the two groups were compared. Differences in viral load between HBV RNA and HBV DNA within each group were compared. Correlations between HBV RNA and HBV DNA, ALT, AST, and TBIL within each group were analyzed. Diagnostic efficacy of HBV RNA for HBV?HCC was determined using receiver operating characteristic (ROC) curve analysis. Results The HBV?HCC group had significantly higher HBV RNA load, HBV RNA positivity rate, ALT, AST and TBIL levels and proportion of male patients and older age compared to the CHB group (P < 0.05). Scatter plot analysis revealed a higher HBV DNA load compared to the HBV RNA load in the CHB group (P < 0.000 1). Correlation analysis showed that HBV RNA was positively correlated with HBV DNA in both groups (P < 0.05). In the CHB group, HBV RNA was positively correlated with ALT, AST and TBIL (P < 0.001). The ROC curve showed that the area under the curve (AUC) for HBV RNA was 0.6923 (P < 0.000 1), with an optimal cut?off value of ≥ 2.5 log10 copies/mL for diagnosing HBV?HCC. Conclusion Serum HBV RNA levels demonstrate high sensitivity and specificity for identifying HBV?HCC and can serve as a reliable indicator for predicting the occurrence of HBV?HCC.

参考文献

[1] POLARIS OBSERVATORY COLLABORATORS. Global prevalence,cascade of care, and pr- ophylaxis coverage of hepatitis B in 2022: A modelling study[J]. Lancet Gastroenterol Hepatol, 2023, 8(10): 879-907.
[2] KOREAN ASSOCIATION FOR THE STUDY OF THE LIVERKASI). KASL clinical practice guidelines for management of chronic hepatitis B[J]. Clin Mol Hepatol, 2022, 28(2): 276-331. doi:10.3350/cmh.2022.0084
[3] 李鸿侠, 孙一萌, 张鸿涛, 等. HBV DNA聚合酶在介导HBV相关肝细胞癌肿瘤细胞免疫 逃逸中的作用[J]. 临床肝胆病杂志, 2023, 39(12): 2858-2866.
[4] 沈晨, 张景, 马鹏飞, 等. HBV相关肝细胞癌组织GLAST、GS蛋白表达及其与切除术后 早期复发转移的关系[J]. 东南大学学报(医学版), 2024, 43(2): 236-242.
[5] ZHANG H, TU T. Approaches to quantifying hepatitis B virus covalently closed circular DNA [J]. Clin Mol Hepatol, 2022, 28 (2): 135-149. doi:10.3350/cmh.2021.0283
[6] ZHUANG A Q, CHEN Y, CHEN S M, et al. Current status and challenges in anti-hepatitis B virus agents based on inactivation/inhibition or elimination of hepatitis B virus covalently closed circular DNA[J]. Viruses, 2023, 15(12): 2315. doi:10.3390/v15122315
[7] HERSHKOVICH L, COTLER S J, SHEKHTMAN L, et al. HBV serum RNA kinetics during nucleic acid polymers based therapy predict functional cure[J]. Antiviral Res, 2025, 234: 106061. doi:10.1016/j.antiviral.2024.106061
[8] RIVEIRO-BARCIELA M, PERICàS J M, BUTI M. How to in terpret viral markers in the management of chronic hepatitis B infection[J]. Clin Microbiol Infect, 2022, 28(3): 355-361. doi:10.1016/j.cmi.2021.10.020
[9] LIU S, DENG R, ZHOU B, et al. Association of Serum Hepatitis B Virus RNA With Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Under Nucleos(t)ide Analogues Therapy[J] J Infect Dis, 2022, 226(5): 881-890. doi:10.1093/infdis/jiab597
[10] MAK L Y, HUANG Q, WONG D K, et al. Residual HBV DNA and pgRNA viraemia is associated with hepatocellular carcinoma in chronic hepatitis B patients on antiviral therapy[J]. J Gastroenterol, 2021, 56(5): 479-488. doi:10.1007/s00535-021-01780-5
[11] 王玉莹. 慢性HBV感染者血清HBV RNA水平与肝细胞癌发生及发展的相关性[D]. 济 南: 山东大学, 2024.
[12] 中华医学会肝病学会分会,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): S18-S39.
[13] 中华人民共和国国家卫生健康委员会医政司. 原发性肝癌诊疗指南(2024年版)[J]. 协和医学杂志, 2024, 15(3): 532-559.
[14] WANG M L, LIAO J, YE F, et al. Distribution and factors associated with serum HBV pregenomic RNA levels in Chinese chronic hepatitis B patients[J]. J Med Virol, 2021, 93(6): 3688-3696. doi:10.1002/jmv.26529
[15] SHEN S, XIE Z, CAI D, et al. Biogenesis and molecular characteristics of serum hepatitis B virus RNA[J]. PLoS Pathog, 2020, 16(10): e1008945. doi:10.1371/journal.ppat.1008945
[16] HONG X, KIM E S, GUO H. Epigenetic regulation of hepatitis B virus covalently closed circular DNA: Implications for epigenetic therapy against chroni chepatitis B[J]. Hepatology, 2017, 66(6): 2066-2077. doi:10.1002/hep.29479
[17] 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
[18] WANG X M, CHI X M, WU R H, et al. Serum HBV RNA correlated with intrahepatic cccDNA more strongly than other HBV markers during peg-interferon treatment[J]. Virol J, 2021, 18(1): 4. doi:10.1186/s12985-020-01471-2
[19] WANG J, YU Y, LI G, et al. Natural history of serum HBV-RNA in chronic HBV infection[J]. J Viral Hepat, 2018, 25(9): 1038-1047. doi:10.1111/jvh.12908
[20] DING W B, WANG M C, YU J,et al. HBV/Pregenomic RNA increases the stemness and promotes the development of HBV-related HCC through reciprocal regulation with insulin-like growth factor 2 mRNA-binding protein 3[J]. Hepatology, 2021, 74(3): 1480-1495. doi:10.1002/hep.31850
[21] XU X, ZHANG L, YE G, et al. Hepatitis B doubly spliced protein(HBDSP) promotes hepatocellular carcinoma cell apoptosis via ETS1/GATA2/YY1-mediated p53 transcription[J]. J Virol, 2023, 97(11): e0108723. doi:10.1128/jvi.01087-23
[22] 朱逸晨, 沙春霞, 樊春笋, 等.慢性乙型肝炎患者发生肝癌的危险因素分析及列线图预测模型[J]. 临床肝胆病杂志, 2024, 40(12): 2441-2449.
[23] FAN R, PAPATHEODORIDIS G, SUN J, et al. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis[J]. J Hepatol, 2020, 73(6): 1368-1378. doi:10.1016/j.jhep.2020.07.025
[24] KIM B K, AHN S H. Prediction model of hepatitis B virus-related hepatocellular carcinoma in patients receiving antiviral therapy[J]. J Formos Med Assoc, 2023, 122(12): 1238-1246. doi:10.1016/j.jfma.2023.05.029
[25] 康娅. 乙肝肝硬化患者肝癌危险因素分析及aMAP和THRI评分在肝癌预测中的价值[D]. 延安:延安大学,2024.
[26] GHANY M G, KING W C, LISKER-MELMAN M, et al. Comparison of HBV RNA and hepatitis B core related antigen with conventional HBV marker samong untreated adults with chronic hepatitis B in North America[J]. Hepatology, 2021, 74(5): 2395-2409. doi:10.1002/hep.32018
[27] GU Y, CHEN L, LIAN Y, et al. Serum HBV pregenomic RNA is correlated with Th1/Th2 immunity in treatment-naive chronic hepatitis B patients[J]. J Med Virol, 2020, 92(3): 317-328. doi:10.1002/jmv.25612
[28] PAPATHEODORIDIS G V, SYPSA V, DALEKOS G N, et al. Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B[J]. J Hepatol, 2020, 72(6): 1088-1096. doi:10.1016/j.jhep.2020.01.007
文章导航

/