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
- 8 Downloads
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.
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)].
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.
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.
KeywordsHepatitis B virus Pegylated-interferon alfa-2a Hepatitis B surface antigen Antivirus
The authors would like to thank the patients and their families for their contribution to this study.
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
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.
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.
All patients signed an informed consent form before screening in accordance with regulatory and local ethics committee requirements.
- 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.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.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