Skip to main content

Advertisement

SpringerLink
Log in

Comparison of HBsAg changes between HBeAg-negative patients who discontinued or maintained entecavir therapy

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Background/purpose

The study compared the hepatitis B surface antigen (HBsAg) changes between hepatitis B e antigen (HBeAg)-negative non-cirrhotic chronic hepatitis B patients who discontinued or maintained entecavir therapy.

Methods

A total of 250 HBeAg-negative, non-cirrhotic patients who were treated with entecavir previously and had stopped treatment for at least 12 months (discontinued group) and 231 HBeAg-negative, non-cirrhotic patients who had received entecavir treatment for at least 4 years (maintained group) were recruited.

Results

In the discontinued group, 71 had a persistent virological suppression (Group I), 35 experienced virological relapse but no clinical relapse or retreatment (Group II), 26 experienced clinical relapse without retreatment (Group III), and 118 experienced HBV relapse and retreatment (Group IV). Patients in Groups I, II, and III, but not in Group IV, experienced a significantly larger drop in HBsAg levels’ post-treatment than during entecavir treatment. Patients in Groups I and III exhibited a greater post-treatment HBsAg decline than patients in Groups II and IV (p < 0.001). Discontinued group experienced a significantly larger drop in HBsAg levels (p < 0.001) and higher HBsAg loss rate (p = 0.001) than maintained group after adjusting for clinical features and HBsAg levels in propensity score matched patients. Patients in maintained group exhibited a smaller drop in HBsAg and lower HBsAg loss rate than patients in groups I, II, and III, but not in Group IV.

Conclusions

Patients who discontinued entecavir therapy and achieved persistent virological suppression exhibited a greater HBsAg decline and higher HBsAg loss rate compared with patients who maintained entecavir therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ALT:

Alanine aminotransferase

CHB:

Chronic hepatitis B

GEE:

Generalized estimating equations

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

NA:

Nucleos(t)ide analogue

PS:

Propensity score

ROC curve:

Receiver-operating characteristic curve

SD:

Standard deviation

ULN:

Upper limit of normal

References

  1. Chen CH, Hu TH, Hung CH, Lu SN, Wang JH, Chang MH, et al. A comparison of four-year entecavir efficacy in nucleos(t)ide analogue-naïve and -experienced adult Taiwanese chronic hepatitis B patients. Hepatol Int. 2013;7:832–43.

    Article  Google Scholar 

  2. Ono A, Suzuki F, Kawamura Y, Sezaki H, Hosaka T, Akuta N, et al. Long-term continuous entecavir therapy in nucleos(t)ide-naïve chronic hepatitis B patients. J Hepatol. 2012;57:508–14.

    Article  CAS  Google Scholar 

  3. Jeng WJ, Sheen IS, Chen YC, Hsu CW, Chien RN, Chu CM, et al. Off therapy durability of response to entecavir therapy in hepatitis B e antigen negative chronic hepatitis B patients. Hepatology. 2013;58:1888–96.

    Article  CAS  Google Scholar 

  4. Chen CH, Lu SN, Hung CH, Wang JH, Hu TH, Changchien CS, et al. The role of hepatitis B surface antigen quantification in predicting HBsAg loss and HBV relapse after discontinuation of lamivudine treatment. J Hepatol. 2014;61:515–22.

    Article  CAS  Google Scholar 

  5. Chen CH, Hung CH, Hu TH, Wang JH, Lu SN, Su PF, et al. Association between level of hepatitis B surface antigen and relapse after entecavir therapy for chronic HBV infection. Clin Gastroenterol Hepatol. 2015;13:1984–92.

    Article  CAS  Google Scholar 

  6. Chen CH, Hung CH, Wang JH, Lu SN, Hu TH, Lee CM. Long-term incidence and predictors of hepatitis B surface antigen loss after discontinuing nucleoside analogues in noncirrhotic chronic hepatitis B patients. Clin Microbiol Infect. 2018;24:997–1003.

    Article  CAS  Google Scholar 

  7. Hadziyannis SJ, Sevastianos V, Rapti I, Vassilopoulos D, Hadziyannis E. Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. Gastroenterology. 2012;143:629–36.

    Article  CAS  Google Scholar 

  8. Hung CH, Wang JH, Lu SN, Hu TH, Lee CM, Chen CH. Hepatitis B surface antigen loss and clinical outcomes between HBeAg-negative cirrhosis patients who discontinued or continued nucleoside analogue therapy. J Viral Hepat. 2017;24:599–607.

    Article  CAS  Google Scholar 

  9. Chen CH, Hung CC, Wang JH, Lu SN, Lai HC, Hu TH, et al. The incidence of hepatitis B surface antigen loss between hepatitis B e antigen-negative non-cirrhotic patients who discontinued or continued entecavir therapy. J Infect Dis. 2019;219:1624–33.

    Article  CAS  Google Scholar 

  10. Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–61.

    Article  Google Scholar 

  11. Hung CH, Lu SN, Wang JH, Lee CM, Chen TM, Tung HD, et al. Correlation between ultrasonographic and pathologic diagnoses of hepatitis B and C virus-related cirrhosis. J Gastroenterol. 2003;38:153–7.

    Article  Google Scholar 

  12. Lee CM, Chen CH, Lu SN, Tung HD, Chou WJ, Wang JH, et al. Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan. Scand J Gastroenterol. 2003;38:95–101.

    Article  CAS  Google Scholar 

  13. Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 2011;10:150–61.

    Article  Google Scholar 

  14. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1–98.

    Article  CAS  Google Scholar 

  15. Berg T, Simon KG, Mauss S, Schott E, Heyne R, Klass DM, et al. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients—FINITE study. J Hepatol. 2017;67:918–24.

    Article  CAS  Google Scholar 

  16. Boni C, Laccabue D, Lampertico P, Giuberti T, Viganò M, Schivazappa S, et al. Restored function of HBV-specific T cells after long-term effective therapy with nucleos(t)ide analogues. Gastroenterology. 2012;143:963–73.

    Article  CAS  Google Scholar 

  17. Rinker F, Zimmer C, Höner Zu Siederdissen C, Manns MP, Kraft ARM, Wedemeyer H, et al. Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B. J Hepatol. 2018;69:584–93.

    Article  CAS  Google Scholar 

  18. Zimmer CL, Rinker F, Höner Zu Siederdissen C, Manns MP, Wedemeyer H, et al. Increased NK cell function after cessation of long-term nucleos(t)ide analogue treatment in chronic hepatitis B is associated with liver damage and HBsAg loss. J Infect Dis. 2018;217:1656–66.

    Article  CAS  Google Scholar 

  19. Liu J, Li T, Zhang L, Xu A. The role of hepatitis B surface antigen in nucleos(t)ide analogues cessation among Asian chronic hepatitis B patients: a systematic review. Hepatology. 2019;70(3):1045–55.

    Article  CAS  Google Scholar 

  20. Su TH, Hu TH, Chen CY, Huang YH, Chuang WL, Lin CC, et al. Four- year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients. Liver Int. 2016;36:1755–64.

    Article  CAS  Google Scholar 

  21. Hosaka T, Suzuki F, Kobayashi M, Seko Y, Kawamura Y, Sezaki H, et al. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology. 2013;58:98–107.

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by Grants CMRPG8G1281 from the Chang Gung Memorial Hospital, Taiwan.

Author information

Authors and Affiliations

  1. Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan

    Chien-Hung Chen, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung & Sheng-Nan Lu

  2. Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan

    Hsueh-Chou Lai & Cheng-Yuan Peng

  3. School of Medicine, China Medical University, Taichung, Taiwan

    Cheng-Yuan Peng

Authors
  1. Chien-Hung Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tsung-Hui Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing-Houng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hsueh-Chou Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chao-Hung Hung
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sheng-Nan Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cheng-Yuan Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Chien-Hung Chen or Cheng-Yuan Peng.

Ethics declarations

Conflict of interest

Cheng-Yuan Peng has served as an advisory committee member for AbbVie, BMS, Gilead, MSD, and Roche. The coauthors Chien-Hung Chen, Tsung-Hui Hu, Jing-Houng Wang, Hsueh-Chou Lai, Chao-Hung Hung, Sheng-Nan Lu have no conflicts of interest to declare.

Ethical approval

This study was conducted in accordance with the 1975 Declaration of Helsinki as revised in 2008. Informed consent was obtained from all patients. The study was approved by the Research Ethics Committees of Chang Gung Memorial Hospital and China Medical University Hospital.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Fig 1.

Flow chart of study population (TIFF 1482 kb)

Supplementary Fig 2.

Comparison of HBsAg changes during and post-entecavir treatment between Group I patients (persistent viral suppression) and Groups II and III patients who achieved persistent viral suppression after transient virological or clinical relapse (TIFF 29 kb)

Supplementary material 3 (DOCX 30 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, CH., Hu, TH., Wang, JH. et al. Comparison of HBsAg changes between HBeAg-negative patients who discontinued or maintained entecavir therapy. Hepatol Int 14, 317–325 (2020). https://doi.org/10.1007/s12072-019-09991-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-019-09991-y

Keywords

Search

Navigation