Advertisement

Pegylated-interferon consolidation treatment versus nucleos(t)ide analogue consolidation treatment in non-cirrhotic hepatitis B patients with hepatitis B e antigen seroconversion: an open-label pilot trial

  • Ying Zhou
  • Rong Yan
  • Guo Qing Ru
  • Li Li Yu
  • Jiong Yao
  • Hong WangEmail author
Original Article
  • 8 Downloads

Abstract

Background

The safety of nucleos(t)ide analogue (NA) treatment cessation remains one of the most controversial topics in the management of chronic hepatitis B (CHB) patients. This study investigated the efficiency of 48-week pegylated-interferon (peg-IFN) alfa-2a consolidation therapy on viral relapse after discontinued NA treatment in CHB patients who achieved hepatitis B e antigen (HBeAg) seroconversion for > 1 year.

Methods

NA-treated HBeAg-positive patients who achieved the standard of discontinued NA treatment (i.e. time of HBeAg seroconversion > 1 year) were randomly assigned to receive peg-IFN consolidation (n = 24) treatment or continue original NA therapy (n = 24) for 48 weeks. The treatments were then discontinued, and the patients were observed up to 144 weeks. The primary endpoint was the proportion of patients with viral relapse at week 144 among those who received at least one dose of study drug or had at least one study visit [modified intention-to-treat population (mITT)].

Results

Of the 24 patients who received peg-IFN treatment, 6 (25%) experienced viral relapse and 8 (36.3%) showed HBsAg loss during 96 weeks of treatment-free follow-up. Of the patients who underwent NA consolidation treatment, only 1 (4.3%) of 23 patients showed HBsAg loss and 14 (58.3%) of 24 patients experienced viral relapse during follow-up. HBsAg level decline < 0.25 log10 IU/mL at week 96 was significantly associated with viral relapse.

Conclusion

A 48-week peg-IFN alfa-2a consolidation therapy increased the rate of HBsAg loss and sustained viral replication suppression in HBeAg-positive patients who achieved HBeAg seroconversion for > 1 year after NA treatment discontinuation.

Keywords

Hepatitis B virus Pegylated-interferon alfa-2a Hepatitis B surface antigen Antivirus 

Notes

Acknowledgements

The authors would like to thank the patients and their families for their contribution to this study.

Author contributions

Hong Wang designed the research. Ying Zhou and Rong Yan collected the data and established the database. Jiong Yao presided over the enrolment and exclusion of the research subjects. Hong Wang analysed the data statistically and drafted the manuscript. Guo Qing Ru and Li Li Yu collected the pathologic data

Funding

The study was supported by a grant from The Science and Technology department of Zhejiang province. NO 2014C33128 and by a grant from Zhejiang provincial health and Family Planning Commission. No C2015W162.

Compliance with ethical standards

Conflict of interest

Ying Zhou, Rong Yan, Guo Qing Ru, Li Li Yu, Jiong Yao and Hong Wang declare that they have no conflict of interesting.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was reviewed and approved by the ethics committee of the hospital.

Informed consent

All patients signed an informed consent form before screening in accordance with regulatory and local ethics committee requirements.

References

  1. 1.
    European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatitis B virus infection. J Hepatol. 2017;67:370–98.CrossRefGoogle Scholar
  2. 2.
    Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, et al. Asian-Pacificconsensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–61.CrossRefGoogle Scholar
  3. 3.
    Lok A, McMahon B. Chronic hepatitis B. Hepatology. 2007;45:507–39.CrossRefGoogle Scholar
  4. 4.
    Yuen MF, Wong DK, Fung J, Ip P, But D, Hung I, et al. HBsAg seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology. 2008;135:1192–9.CrossRefGoogle Scholar
  5. 5.
    Han Meifang, Jiang Jiaji, Hou Jinlin, Tan Deming, Sun Yongtao, Zhao Mianzhi, et al. Sustained immune control in HbeAg positive patients who switched from entecavir therapy to pegylated interferon-2a:1 year follow-up of the OSST study. Antiviral Therapy. 2016;21:337–44.CrossRefGoogle Scholar
  6. 6.
    Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261.CrossRefGoogle Scholar
  7. 7.
    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.CrossRefGoogle Scholar
  8. 8.
    Yeh CT, Hsu CW, Chen YC, Liaw YF. Withdrawal of lamivudine in HBeAg-positive chronic hepatitis B patients after achieving effective maintained virological suppression. J Clin Virol. 2009;45:114–8.CrossRefGoogle Scholar
  9. 9.
    Chaung KT, Ha NB, Trinh HN, Garcia RT, Nguyen HA, Nguyen KK, et al. High frequency of recurrent viremia after hepatitis B e antigen seroconversion and consolidation therapy. J Clin Gastroenterol. 2012;46:865–70.CrossRefGoogle Scholar
  10. 10.
    Ridruejo E, Silva MO. Safety of long-term nucleos(t)ide treatment in chronic hepatitis B. Expert Opin Drug Saf. 2012;11:357–60.CrossRefGoogle Scholar
  11. 11.
    Petersen J, Dandri M. Optimal therapy for chronic hepatitis B: hepatitis B virus combination therapy? Liver Int. 2015;35(Suppl. 1):114–20.CrossRefGoogle Scholar
  12. 12.
    Thimme R, Dandri M. Dissecting the divergent effects of interferon-alpha on immune cells: time to rethink combination therapy in chronic hepatitis B? J Hepatol. 2013;58:205–9.CrossRefGoogle Scholar
  13. 13.
    Ning Q, Han M, Sun Y, et al. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol. 2014;61:777–84.  https://doi.org/10.1016/j.jhep.2014.05.044.CrossRefGoogle Scholar
  14. 14.
    Brouwer WP, Xie Q, Sonneveld MJ, Zhang N, Zhang Q, Tabak F, et al. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: a multicenter randomized trial (ARES study). Hepatology. 2015;61:1512–22.  https://doi.org/10.1002/hep.27586.CrossRefGoogle Scholar
  15. 15.
    Lim SG, Yang WL, Ngu J, Tan J, Ahmed TT, Dan YY, et al. Switch or add-on peginterferon for chronic hepatitis B patients already on nucleos(t)ide analogue therapy (SWAP study): provisional analysis—add-on therapy superior. J Hepatol. 2017;66:S60.  https://doi.org/10.1016/S0168-8278(17)30382-3.CrossRefGoogle Scholar
  16. 16.
    Micco Lorenzo, Peppa Dimitra, Loggi Elisabetta, Schurich Anna, Jefferson Lucy, et al. Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B. J Hepatol. 2013;58:225–33.  https://doi.org/10.1016/j.jhep.2012.11.007.CrossRefGoogle Scholar
  17. 17.
    Peng Hu, Shang Jia, Zhang Wenhong, Gong Guozhong, Li Yongguo, Chen Xinyue, et al. HBsAg loss with Peg-interferon Alfa-2a in Hepatitis B patients with partial response to nucleos(t)ide analog: new switch study. J Clin Transl Hepatol. 2018;6:1–10.  https://doi.org/10.14218/JCTH.2017.00072.Google Scholar
  18. 18.
    Boni C, Laccabue D, Lampertico P, Giuberti T, Vigano 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.CrossRefGoogle Scholar
  19. 19.
    Buster EH, Flink HJ, Cakaloglu Y, Simon K, Trojan J, Tabak F, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2 b. Gastroenterology. 2008;135:459–67.CrossRefGoogle Scholar
  20. 20.
    Janssen HLA, van Zonneveld M, Senturk H, et al. Pegylated interferonalfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005;365:123–9.CrossRefGoogle Scholar
  21. 21.
    Vigan M, Invernizzi F, Grossi G, Lampertico P. Review article: the potential of interferon and nucleos(t)ide analogue combination therapy in chronic hepatitis B infection. Aliment Pharmacol Ther. 2016;44:653–61.CrossRefGoogle Scholar
  22. 22.
    Marcellin P, Ahn SH, Ma X, et al. Combination of tenofovir disoproxil fumarate and peginterferon α-2a increases loss of hepatitis B surface antigen in patients with chronic hepatitis B. Gastroenterology. 2016;150:134–44.CrossRefGoogle Scholar
  23. 23.
    Takkenberg RB, Jansen L, de Niet A, et al. Baseline hepatitis B surface antigen (HBsAg) as predictor of sustained HBsAg loss in chronic hepatitis B patients treated with peginterferon alfa-2a and adefovir. Antivir Ther. 2013;18:895–904.CrossRefGoogle Scholar
  24. 24.
    Piratvisuth T, Marcellin P, Pepescu M, Kapprell HP, Rothe V, Lu ZM. Hepatitis B surface antigen: association with sustained response to peginterferon alfa-2a in hepatitis B e-antigen-positive patients. Hepatol Int. 2013;7:429–36.CrossRefGoogle Scholar
  25. 25.
    Chen CH, Lu SN, Hung CH, Wang JH, Hu TH, Chang Chien 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.CrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2019

Authors and Affiliations

  • Ying Zhou
    • 1
  • Rong Yan
    • 1
  • Guo Qing Ru
    • 2
  • Li Li Yu
    • 2
  • Jiong Yao
    • 3
  • Hong Wang
    • 1
    Email author
  1. 1.Department of Infectious Diseases, Zhejiang Provincial People’s HospitalPeople’s Hospital Hang Zhou Medical CollegeZhejiangChina
  2. 2.Department of Pathology, Zhejiang Provincial People’s HospitalPeople’s Hospital Hang Zhou Medical CollegeZhejiangChina
  3. 3.Department of Medical Record Statistic Information, Zhejiang Provincial People’s HospitalPeople’s Hospital Hang Zhou Medical CollegeZhejiangChina

Personalised recommendations