Effect of pegylated interferon alfa-2a in HBeAg-negative chronic hepatitis B during and 48 weeks after off-treatment follow-up: the limitation of pre-treatment HBsAg load for the seroclearance of HBsAg

Abstract

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The study aimed to evaluate the efficacy of pegylated interferon (Peg-IFN) alfa-2a treatment for seroclearance of HBs antigen (HBsAg) in HBe antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. This retrospective study investigated 16 HBeAg-negative CHB patients who received Peg-IFN alfa-2a weekly for 48 weeks. Thereafter, the patients were followed-up for 48 weeks after the end of therapy. The following criteria were also used for inclusion: HBV-DNA < 5.0 log copies/mL and without nucleot(s)ide analogs. Four HBsAg-positive cases became HBsAg negative. The HBsAg levels of the 4 patients who achieved HBsAg seroclearance were lower significantly than that of the non-seroclearance group (p = 0.007). The mean HBsAg levels in these 4 cases were 68 IU/mL, while the mean HBsAg levels in the non-seroclearance group were 2,114 IU/mL. The mean HBV-DNA levels in the 4 HBsAg seroclearance cases were 2.8 log copies/mL as compared to 3.6 log copies/mL in HBsAg-non-seroclearance cases (p = 0.01). Cases that are HBeAg negative, with HBV-DNA levels < 5 log copies/mL, and HBsAg titers < 120 IU/mL cases may achieve HBsAg clearance with Peg-IFN therapy.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. 1.

    Trépo C, Chan HLY, Lok A (2014) Hepatitis B virus infection. Lancet 384:2053–2063

    Article  PubMed  Google Scholar 

  2. 2.

    Lavanchy D (2004) Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 11:97–107

    CAS  Article  Google Scholar 

  3. 3.

    Chen CJ, Yu MW, Liaw YF (1997) Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastoenterol Hepatol 12:294–298

    Article  Google Scholar 

  4. 4.

    Chen CJ, Yang HI, Su J et al (2006) Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295:65–73

    CAS  Article  Google Scholar 

  5. 5.

    Martinot-Peignoux M, Lapalus M, Laouénan C et al (2013) Prediction of disease reactivation in asymptomatic hepatitis B e antigen-negative chronic hepatitis B patients using baseline serum measurements of HBsAg and HBV-DNA. J ClinVirol 58:401–407

    CAS  Google Scholar 

  6. 6.

    Qu LS, Liu JX, Zhang HF, Zhu J, Lu CH (2015) Effect of serum hepatitis B surface antigen levels on predicting the clinical outcomes of chronic hepatitis B infection: a meta-analysis. Hepatol Res 45:1004–1013

    CAS  Article  Google Scholar 

  7. 7.

    Ono A, Suzuki F, Kawamura Y (2012) Long-term continuous entecavir therapy in nucleos(t)ide-naïve chronic hepatitis B patients. J Hepatol 57:508–514

    CAS  Article  Google Scholar 

  8. 8.

    Tseng TC, Liu CJ, Yang HC et al (2012) High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology 142:1140–1149

    CAS  Article  Google Scholar 

  9. 9.

    Liu WR, Tian MX, Jin L et al (2015) High levels of hepatitis b surface antigen are associated with poorer survival and early recurrence of hepatocellular carcinoma in patients with low hepatitis B viral loads. Ann Surg Oncol 22:843–850

    Article  Google Scholar 

  10. 10.

    Hara T, Suzuki F, Kawamura Y et al (2014) Long-term entecavir therapy results in falls in serum hepatitis B surface antigen levels and seroclearance in nucleos(t)ide-naïve chronic hepatitis B patients. J Viral Hepat 21:802–808

    CAS  Article  Google Scholar 

  11. 11.

    Brunetto MR, Moriconi F, Bonino F (2009) Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B. Hepatology 49:1141–1150

    CAS  Article  Google Scholar 

  12. 12.

    Chen JD, Yang HI, Iloeje UH et al (2010) Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 138:1747–1754

    Article  Google Scholar 

  13. 13.

    Moucari R, Korevaar A, Lada O et al (2009) High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol 50:1084–1092

    CAS  Article  Google Scholar 

  14. 14.

    Rijckborst V, Hansen B, Cakaloglu Y et al (2010) Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels. Hepatology 52:454–461

    CAS  Article  Google Scholar 

  15. 15.

    Tseng TC, Liu CJ, Yang HC et al (2013) Serum hepatitis B surface antigen levels help predict disease progression in patients with low hepatitis B virus loads. Hepatology 57:441–450

    CAS  Article  Google Scholar 

  16. 16.

    Tseng TC, Liu CJ, Chen CL et al (2013) Risk stratification of hepatocellular carcinoma in hepatitis B virus e antigen-negative carriers by combining viral biomarkers. J Infect Dis 208:584–593

    CAS  Article  Google Scholar 

  17. 17.

    Sarin SK, Kumar M, Lau GK et al (2016) Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 10:1–98

    CAS  Article  Google Scholar 

  18. 18.

    Kobayashi M, Hosaka T, Suzuki F, Akuta N et al (2014) Seroclearance rate of hepatitis B surface antigen in 2,112 patients with chronic hepatitis in Japan during long-term follow-up. J Gastroenterol 49:538–546

    CAS  Article  Google Scholar 

  19. 19.

    Li MH, Zhang L, Qu XJ et al (2017) Kinetics of hepatitis B surface antigen level in chronic hepatitis B patients who achieved hepatitis B surface antigen loss during pegylated interferon alpha-2a treatment. Med J (Engl) 130:559–565

    CAS  Google Scholar 

  20. 20.

    Moucari R, Mackiewicz V, Lada O et al (2009) Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology 49:1151–1157

    CAS  Article  Google Scholar 

  21. 21.

    Wedemeyer H, Yurdaydin C, Dalekos GN et al (2011) Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med 364:322–331

    CAS  Article  Google Scholar 

  22. 22.

    Marcellin P, Avila C, Wursthorn K et al (2015) Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy. J Hepatol 62:41–47

    CAS  Article  Google Scholar 

  23. 23.

    Boglione L, D’Avolio A, Cariti G et al (2013) Sequential therapy with entecavir and PEG-INF in patients affected by chronic hepatitis B and high levels of HBV-DNA with non-D genotypes. J Viral Hepat 20:11–19

    Article  Google Scholar 

  24. 24.

    Jaroszewicz J, Ho H, Markova A et al (2011) B surface antigen (HBsAg) decrease and serum interferon-inducible protein-10 levels as predictive markers for HBsAg loss during treatment with nucleoside/nucleotide analogues. Antivir Ther 16:915–924

    CAS  Article  Google Scholar 

  25. 25.

    Kittner JM, Sprinzl MF, Grambihler A et al (2012) Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B. J Clin Virol 54:93–95

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank the technical assistants of the Department of Gastroenterology, Kagawa University.

Funding

This research was not directly funded.

Author information

Affiliations

Authors

Contributions

SM: Conceptualization, formal analysis, writing—original draft. KF: Investigation, methodology. KT: Investigation. MN: Investigation. KO: Investigation. TT: Investigation. HK: Investigation. JT: Investigation. AM: Investigation. TH: Supervision. TM: Conceptualization, writing—review and editing, supervision, project administration.

Corresponding author

Correspondence to Shima Mimura.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Ethical approval for this study was obtained from ethical committee of Kagawa University, Japan.

Human and animal rights statement

All procedures performed in the study 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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mimura, S., Fujita, K., Takuma, K. et al. Effect of pegylated interferon alfa-2a in HBeAg-negative chronic hepatitis B during and 48 weeks after off-treatment follow-up: the limitation of pre-treatment HBsAg load for the seroclearance of HBsAg. Intern Emerg Med (2021). https://doi.org/10.1007/s11739-020-02622-7

Download citation

Keywords

  • Peg-IFN
  • HBeAg negative
  • Chronic hepatitis B
  • HBsAg