End-of-treatment anti-HBs levels and HBeAg status identify durability of HBsAg loss after PEG-IFN discontinuation

Yifei Guo; Jiajia Han; Yongmei Zhang; Chengmeng Jin; Yao Zhang; Jingjing He; Shiqi Chen; Yue Guo; Yanxue Lin; Fahong Li; Feifei Yang; Zhongliang Shen; Richeng Mao; Haoxiang Zhu; Jiming Zhang

doi:10.3389/fcimb.2023.1120300

End-of-treatment anti-HBs levels and HBeAg status identify durability of HBsAg loss after PEG-IFN discontinuation

Front Cell Infect Microbiol. 2023 Feb 24:13:1120300. doi: 10.3389/fcimb.2023.1120300. eCollection 2023.

Authors

Yifei Guo¹, Jiajia Han¹, Yongmei Zhang¹, Chengmeng Jin², Yao Zhang¹, Jingjing He¹, Shiqi Chen¹, Yue Guo¹, Yanxue Lin¹, Fahong Li¹, Feifei Yang¹, Zhongliang Shen¹, Richeng Mao¹, Haoxiang Zhu¹, Jiming Zhang^{1

3

4}

Affiliations

¹ Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
² Department of Medical Microbiology and Parasitology, School of Medical Sciences, Fudan University, Shanghai, China.
³ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
⁴ Department of Infectious Diseases, Jing'An Branch of Huashan Hospital, Fudan University, Shanghai, China.

Abstract

Background: Hepatitis B surface antigen (HBsAg) loss, namely, the functional cure, can be achieved through the pegylated interferon (PEG-IFN)-based therapy. However, it is an unignorable fact that a small proportion of patients who achieved functional cure develop HBsAg reversion (HRV) and the related factors are not well described.

Methods: A total of 112 patients who achieved PEG-IFN-induced HBsAg loss were recruited. HBV biomarkers and biochemical parameters were examined dynamically. HBV RNA levels were assessed in the cross-sectional analysis. The primary endpoint was HRV, defined as the reappearance of HBsAg after PEG-IFN discontinuation.

Results: HRV occurred in 17 patients during the follow-up period. Univariable analysis indicated that hepatitis B e antigen (HBeAg) status, different levels of hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) at the end of PEG-IFN treatment (EOT) were significantly associated with the incidence of HRV through using the log-rank test. Additionally, time-dependent receiver operating characteristic (ROC) analysis showed that the anti-HBs was superior to anti-HBc in predictive power for the incidence of HRV during the follow-up period. Multivariable Cox proportional hazard analysis found that anti-HBs ≥1.3 log₁₀IU/L (hazard ratio (HR), 0.148; 95% confidence interval (CI), 0.044-0.502) and HBeAg negativity (HR, 0.183; 95% CI, 0.052-0.639) at EOT were independently associated with lower incidence of HRV. Cross-sectional analysis indicated that the HBV RNA levels were significantly correlated with the HBsAg levels in patients with HRV (r=0.86, p=0.003).

Conclusions: EOT HBeAg negativity and anti-HBs ≥1.3 log₁₀IU/L identify the low risk of HRV after PEG-IFN discontinuation.

Keywords: HBeAg; HBsAg reversion; PEG-IFN; anti-HBs; chronic hepatitis B; functional cure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / therapeutic use
Cross-Sectional Studies
DNA, Viral
Hepatitis B Antibodies / therapeutic use
Hepatitis B Surface Antigens*
Hepatitis B e Antigens / therapeutic use
Hepatitis B virus / genetics
Hepatitis B, Chronic* / drug therapy
Humans
Interferon-alpha / therapeutic use
Polyethylene Glycols / therapeutic use
Recombinant Proteins / therapeutic use
Treatment Outcome

Substances

Hepatitis B Surface Antigens
Hepatitis B e Antigens
Interferon-alpha
Antiviral Agents
Polyethylene Glycols
Hepatitis B Antibodies
DNA, Viral
Recombinant Proteins

Grants and funding

This work was supported by the National Natural Science Foundation of China under Grant No. 81871640, 82172255, Shanghai Municipal Science and Technology Major Project (ZD2021CY001) and Shanghai Key Clinical Specialty Construction Program (ZK2019B24).