您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2025, Vol. 63 ›› Issue (3): 85-91.doi: 10.6040/j.issn.1671-7554.0.2024.1035

• 临床医学 • 上一篇    

HBeAg阳性慢性乙型肝炎低病毒血症患者HBV RNA状态及干预后变化

张域爽,吴娟丽,高涵,张毅恒,李涛,王磊   

  1. 山东大学第二医院肝病科, 山东 济南 250033
  • 发布日期:2025-04-08
  • 通讯作者: 王磊. E-mail:wlcrb@sdu.edu.cn
  • 基金资助:
    山东省自然科学基金项目(ZR2019PH052);山东大学临床研究基金(6010220082)

HBV RNA status and changes after intervention in HBeAg-positive chronic hepatitis B patients with low level viremia

ZHANG Yushuang, WU Juanli, GAO Han, ZHANG Yiheng, LI Tao, WANG Lei   

  1. Department of Hepatology, The Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Published:2025-04-08

摘要: 目的 探讨核苷(酸)类似物(nucleoside/nucleotide analogues, NAs)治疗后乙型肝炎e抗原(hepatitis B e antigen, HBeAg)阳性慢性乙型肝炎低病毒血症(low-level viremia, LLV)患者的血清乙型肝炎病毒RNA(hepatitis B virus RNA, HBV RNA)水平及其在NAs干预后的变化。 方法 采用巢式病例对照研究,根据LLV病例数1∶1匹配抗病毒治疗后达到维持病毒学应答(maintained virological response, MVR)患者。共纳入62例LLV及62例MVR患者。根据患者治疗意愿将LLV患者分为NAs维持治疗组及更改方案组,收集其临床资料并进行随访。通过实时荧光恒温扩增检测技术(simultaneous amplification and testing, SAT)对血清HBV RNA进行定量检测。 结果 与MVR组患者相比,LLV组在基线、随访24周及48周时血清HBV RNA水平均较高(P均<0.001)。随访期间LLV患者血清HBV RNA水平较基线有所下降,差异无统计学意义(P均>0.05)。LLV患者在维持治疗组和更改方案组随访至24、48周时血清HBV RNA变化幅度仅在更改方案组的48时有所下降,差异无统计学意义(P均>0.05)。 结论 与MVR组相比,LLV患者血清HBV RNA水平更高且下降缓慢,调整NAs治疗后HBV RNA水平较维持方案组下降并不明显,提示需要联合其它干预措施以进一步降低HBV转录活性。

关键词: 低病毒血症, 维持病毒学应答, 乙型肝炎病毒RNA, 核苷(酸)类似物, 乙型肝炎e抗原

Abstract: Objective To investigate serum HBV RNA levels in HBeAg-positive chronic hepatitis B patients with low-level viremia(LLV)following long-term nucleoside/nucleotide analogues(NAs)therapy and to assess changes after NAs intervention. Methods This was a nested case-control study and patients with LLV were matched 1∶1 with who achieved a maintained virological response(MVR)after antiviral therapy. LLV patients were then categorized into an NAs intervention group and a control group based on their willingness to undergo further treatment. Clinical data were collected and followed up. Serum HBV RNA was quantified using the Specific RNA Target Capture combined with the Simultaneous Amplification and Testing(SAT)method. Results A total of 62 LLV patients and 62 MVR patients were enrolled. Serum HBV RNA levels are higher in the LLV group compared with the MVR group at baseline, 24 weeks and 48 weeks of follow-up(P<0.001). During the follow-up period, serum HBV RNA decreased from baseline in the LLV patients, but the results were not statistically different. The decrease in serum HBV RNA changes in LLV patients in the control and intervention groups followed up to 24 and 48 weeks only decreased in the intervention group at 48 weeks, but there was no statistically significant difference. Conclusion Serum HBV RNA levels are higher in the LLV patients compared to the MVR group and decline slowly. The decrease in HBV RNA levels after adjustment for NAs treatment is not significant compared to the maintained regimen group. It is suggested that combinations of other interventions are necessary to further reduce HBV transcriptional activity.

Key words: Low-level viremia, Maintained virological response, Hepatitis B virus RNA, Nucleoside/ nucleotide analogues, Hepatitis B e antigen

中图分类号: 

  • R512.6+2
[1] Fattovich G. Natural history and prognosis of hepatitis B[J]. Semin Liver Dis, 2003, 23(1): 47-58.
[2] Organization WH. Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection(text extract): executive summary[J]. Infect Dis Immun, 2024, 4(3): 103-105.
[3] 范玉琛. 乙型肝炎病毒母婴传播预防研究进展[J]. 山东大学学报(医学版), 2021, 59(5): 46-51, 67. FAN Yuchen. Current progress on prevention of mother to child transmission of hepatitis B virus[J]. Journal of Shandong University(Health Sciences), 2021, 59(5): 46-51, 67.
[4] Chen H, Fu JJ, Li L, et al. Risk factors of low-level viremia in chronic hepatitis B patients receiving Entecavir monotherapy: a retrospective cohort study[J]. J Gastroenterol Hepatol, 2024, 39(1): 180-184.
[5] Kim JH, Sinn DH, Kang W, et al. Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment[J]. Hepatology, 2017, 66(2): 335-343.
[6] Mak LY, Huang Q, Wong DK, 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.
[7] Sun FR, Liu ZF, Wang BY. Correlation between low-level viremia and hepatitis B-related hepatocellular carcinoma and recurrence: a retrospective study[J]. BMC Cancer, 2021, 21(1): 1103.
[8] Zhang Q, Peng H, Liu XQ, et al. Chronic hepatitis B infection with low level viremia correlates with the progression of the liver disease[J]. J Clin Transl Hepatol, 2021, 9(6): 850-859.
[9] Deng R, Liu S, Shen S, et al. Circulating HBV RNA: From biology to clinical applications[J]. Hepatology, 2022, 76(5): 1520-1530.
[10] Wang J, Shen T, Huang XB, 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.
[11] Hong XP, Hu JM. Serum HBV RNA composition dynamics as a marker for intrahepatic HBV cccDNA turnover[J]. J Med Virol, 2020, 92(8): 935-937.
[12] Fan R, Zhou B, Xu M, et al. Association between negative results from tests for HBV DNA and RNA and durability of response after discontinuation of nucles(t)ide analogue therapy[J]. Clin Gastroenterol Hepatol, 2020, 18(3): 719-727.
[13] Ghany MG, King WC, Lisker-Melman M, et al. Comparison of HBV RNA and hepatitis B core related antigen with conventional HBV markers among untreated adults with chronic hepatitis B in North America[J]. Hepatology, 2021, 74(5): 2395-2409.
[14] Ji X, Xia MY, Zhou B, et al. Serum hepatitis B virus RNA levels predict HBeAg seroconversion and virological response in chronic hepatitis B patients with high viral load treated with nucleos(t)ide analog[J]. Infect Drug Resist, 2020, 22,(13): 1881-1888.
[15] Liu YY, Jiang M, Xue JY, et al. Serum HBV RNA quantification: useful for monitoring natural history of chronic hepatitis B infection[J].BMC Gastroenterol, 2019, 19(1): 53.
[16] Xia MY, Chi H, Wu YB, et al. Serum hepatitis B virus RNA level is associated with biochemical relapse in patients with chronic hepatitis B infection who discontinue nucleos(t)ide analogue treatment[J]. Aliment Pharmacol Ther, 2021, 54(5): 709-714.
[17] You H, Wang FS, Li TS, et al. Guidelines for the prevention and treatment of chronic hepatitis B(version 2022)[J]. J Clin Transl Hepatol, 2023, 11(6): 1425-1442.
[18] Luo H, Zhang XX, Cao LH, et al. Serum hepatitis B virus RNA is a predictor of HBeAg seroconversion and virological response with entecavir treatment in chronic hepatitis B patients[J]. World J Gastroenterol, 2019, 25(6): 719-728.
[19] Li T, Chen Y, Zhang YS, et al. Elevated hepatitis B virus RNA levels in HBeAg-positive patients with low-level viraemia or previous low-level viraemia[J]. J Viral Hepat, 2024, 31(8): 504-507.
[20] Sun YM, Wu XN, Zhou JL, et al. Persistent low level of hepatitis B virus promotes fibrosis progression during therapy[J]. Clin Gastroenterol Hepatol, 2020, 18(11): 2582-2591.
[21] Zhang Q, Peng H, Liu XQ, et al. Chronic hepatitis B infection with low level viremia correlates with the progression of the liver disease[J]. J Clin Transl Hepatol, 2021, 9(6): 850-859.
[22] Terrault NA, Bzowej NH, Chang KM, et al. AASLD guidelines for treatment of chronic hepatitis B[J]. Hepatology, 2016, 63(1): 261-283.
[23] European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2): 370-398.
[24] Yin GQ, Li J, Zhong B, et al. New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection: Increase of entecavir dosage[J]. World J Gastroenterol, 2021, 27(8): 666-676.
[25] Yim HJ, Kim IH, Suh SJ, et al. Switching to tenofovir vs continuing entecavir for hepatitis B virus with partial virologic response to entecavir: a randomized controlled trial[J]. J Viral Hepat, 2018, 25(11): 1321-1330.
[26] Chen J, Zhao SS, Liu XX, et al. Comparison of the efficacy of tenofovir versus tenofovir plus entecavir in the treatment of chronic hepatitis B in patients with poor efficacy of entecavir: a systematic review and meta-analysis[J]. Clin Ther, 2017, 39(9): 1870-1880.
[27] Wang YH, Liao J, Zhang DM, et al. Tenofovir monotherapy versus tenofovir plus entecavir combination therapy in HBeAg-positive chronic hepatitis patients with partial virological response to entecavir[J]. J Med Virol, 2020, 92(3): 302-308.
[28] Yamada S, Uchida Y, Kouyama JI, et al. Switching from combination therapy with entecavir hydrate plus tenofovir alafenamide fumarate to tenofovir alafenamide fumarate monotherapy in patients with chronic hepatitis B based on nucleotide sequences of hepatitis B virus pregenome RNA[J]. Hepatol Res, 2024, 54(10): 877-887.
[29] 李光海. NAs治疗慢乙肝低病毒血症危险因素分析及治疗策略选择[D]. 海口: 海南医学院, 2023.
[30] 王玉珊. 探讨不同转换治疗策略对经治慢乙肝低病毒血症患者疗效转归的影响: 单中心回顾性研究[D]. 兰州: 兰州大学, 2022.
[31] 张培星. 恩替卡韦/替诺福韦酯经治慢乙肝患者发生低病毒血症的相关影响因素和治疗策略分析研究[D]. 湛江: 广东医科大学, 2023.
[32] 胡鹏,尚佳,张文宏,等. 核苷(酸)类似物治疗部分应答的乙型肝炎患者通过聚乙二醇干扰素α-2a治疗获得HBsAg消失:New Switch研究[J]. 中华肝脏病杂志,2018, 26(10): 756-764. HU Peng, SHANG Jia, ZHANG Wenhong, et al. HBsAg loss with Pegylated-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)-ide analog: new switch study[J]. Chinese Journal of Hepatology, 2018, 26(10): 756-764.
[33] Yeh ML, Huang JF, Yu ML, et al. Hepatitis b infection: progress in identifying patients most likely to respond to peginterferon Alfa[J]. Expert Rev Gastroenterol Hepatol, 2021, 15(4): 427-435.
[34] Zoutendijk R, Reijnders JGP, Brown A, et al. Entecavir treatment for chronic hepatitis B: adaptation is not needed for the majority of naïve patients with a partial virological response[J]. Hepatology, 2011, 54(2): 443-451.
[35] Chaung KT, OBrien C, Ha NB, et al. Alternative therapies for chronic hepatitis B patients with partial virological response to standard entecavir monotherapy[J]. J Clin Gastroenterol, 2016, 50(4): 338-344.
[1] 孙海平,王磊,杨芳. 核苷(酸)类似物相关HBV P基因区耐药变异的焦磷酸测序[J]. 山东大学学报(医学版), 2010, 48(5): 85-.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!