Abstract
Background
The global burden of chronic hepatitis B remains high and the best possible treatment remains long-term viral suppression expecting cure.
Methods
Total 154 patients of chronic hepatitis B (48 HBeAg positive, e + ve) treated with oral entecavir (0.5 mg/1 mg per day) were recruited from June 2007 and followed prospectively until December 2022 for persistent HBV DNA negativity, HBeAg and HBsAg loss/seroconversion and other liver and drug-related events in real-life settings.
Results
The mean duration of therapy was 6.78 (2–14) years with 1364 person-years of follow-up. All patients were HBV DNA negative by 15 months and remained so until the last follow-up. As many as 16.7% lost HBeAg after eight to 13 years of therapy, but not HBsAg. The mean fall in serum HBsAg level per year was 0.158 log IU/mL, being significantly higher in e + ve patients at baseline and until two years of therapy. The decline was significant until six years in e + ve patients compared to two years in e − ve ones. None had biochemical or virological breakthrough (except eight defaulters), flares or any untoward effects. The incidence of liver-related events, hepatocellular carcinoma and death was 10.4%, 1.9% and 14.3%, respectively, and 5.2% deaths were liver-related whose predictors were presence of cirrhosis (log rank 46.5, p > 0.001) and higher HBsAg level > 4 log IU/mL (log rank 18.15, p < 0.001) at baseline.
Conclusion
Long-term entecavir therapy provides additional benefits of continuous reduction of serum HBsAg levels beyond suppression of HBV DNA.
Graphical Abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Data confidential, available on demand.
References
Hepatitis B [https://www.who.int/news-room/fact-sheets/detail/hepatitis B]. Accessed 14/07/2023.
World Health Organization (WHO). Global hepatitis report. 2017;2017: 83.
Yoshida K, Enomoto M, Tamori A, Nishiguchi S, Kawada N. Combination of entecavir or tenofovir with pegylated interferon-α for long-term reduction in hepatitis B surface antigen levels: simultaneous, sequential, or add-on combination therapy. Int J Mol Sci. 2021;22:1456.
Grossi G, Viganò M, Loglio A, Lampertico P. Hepatitis B virus long-term impact of antiviral therapy nucleot(s)ide analogues (NUCs). Liver Int. 2017;37 Suppl. 1:45–51.
Chien RN, Liaw YF. Current trend in antiviral therapy for chronic hepatitis B. Viruses. 2022;14:434.
Broquetas T, Carrión JA. Current perspectives on nucleos(t)ide analogue therapy for the long-term treatment of hepatitis B virus. Hepat Med. 2022;14:87–100.
Hou JL, Zhao W, Lee C, et al. Outcomes of long-term treatment of chronic HBV infection with entecavir or other agents from a randomized trial in 24 countries. Clin Gastroenterol Hepatol. 2020;18:457–67.e21.
Suzuki F, Hosaka T, Suzuki Y, et al. Long-term outcome of entecavir treatment of nucleos(t)ide analogue-naïve chronic hepatitis B patients in Japan. J Gastroenterol. 2019;54:182–93.
Cho JY, Sohn W, Sinn DH, et al. Long-term real-world entecavir therapy in treatment-naïve hepatitis B patients: base-line hepatitis B virus DNA and hepatitis B surface antigen levels predict virologic response. Korean J Intern Med. 2017;32:636–46.
Collo A, Belci P, Fagoonee S, et al. Efficacy and safety of long-term entecavir therapy in a European population. Minerva Gastroenterol Dietol. 2018;64:201–7.
Huang ZH, Lu GY, Qiu LX, et al. Risk of hepatocellular carcinoma in antiviral treatment-naïve chronic hepatitis B patients treated with entecavir or tenofovir disoproxil fumarate: a network meta-analysis. BMC Cancer. 2022;22:287.
Goyal SK, Dixit VK, Shukla SK, et al. Prolonged use of tenofovir and entecavir in hepatitis B virus-related cirrhosis. Indian J Gastroenterol. 2015;34:286–91.
Papatheodoridis G, Goulis J, Manolakopoulos S, et al. Changes of HBsAg and interferon-inducible protein 10 serum levels in naive HBeAg-negative chronic hepatitis B patients under 4-year entecavir therapy. J Hepatol. 2014;60:62–8.
Lam YF, Seto WK, Wong D, et al. Seven-year treatment outcome of entecavir in a real-world cohort: effects on clinical parameters, HBsAg and HBcrAg levels. Clin Transl Gastroenterol. 2017;8:e125.
Hirode G, Choi HSJ, Chen CH, et al. Off-therapy response after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B: an international, multicenter, multiethnic cohort (RETRACT-B Study). Gastroenterology. 2022;162:757–71.e4.
Chon YE, Kim SU, Seo YS, et al. Long-term effects of entecavir and tenofovir treatment on the fibrotic burden in patients with chronic hepatitis B. J Gastroenterol Hepatol. 2022;37:200–7.
Tseng TC, Liu CJ, Yang HC, et al. Serum hepatitis B surface antigen levels help predict disease progression in patients with low hepatitis B virus loads. Hepatology. 2013;57:441–50.
Lai CL, Wong DK, Wong GT, Seto WK, Fung J, Yuen MF. Rebound of HBV DNA after cessation of nucleos/tide analogues in chronic hepatitis B patients with undetectable covalently closed circular DNA. JHEP Rep. 2020;2:100112.
Chi H, Arends P, Reijnders JG, et al. VIRGIL Surveillance Study Group (European Surveillance Network for Vigilance Against Viral Resistance). Flares during long-term entecavir therapy in chronic hepatitis B. J Gastroenterol Hepatol. 2016;31:1882–7.
Ray G. Current scenario of hepatitis B and its treatment in India. J Clin Transl Hepatol. 2017;5:277–96.
Ray G. 5-year efficacy of entecavir in Indian patients with chronic hepatitis B. Indian J Gastroenterol. 2016;35:190–4.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
GR declares no competing interests.
Ethics statement
The study was performed conforming to the Helsinki Declaration of 1975, as revised in 2000 and 2008 concerning human and animal rights, and the authors followed the policy concerning informed consent as shown on Springer.com.
Ethics approval, consent to participate, and consent for publication
Ethics approval and consent to participate and for publication were taken.
Disclaimer
The author is solely responsible for the data and the contents of the paper. In no way, the Honorary Editor-in-Chief, Editorial Board Members, the Indian Society of Gastroenterology or the printer/publishers are responsible for the results/findings and content of this article.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Ray, G. Long-term entecavir therapy of chronic hepatitis B in real-life setting—Importance of quantitative HBsAg level. Indian J Gastroenterol (2023). https://doi.org/10.1007/s12664-023-01480-3
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12664-023-01480-3