Case Control Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 26, 2021; 9(21): 5812-5821
Published online Jul 26, 2021. doi: 10.12998/wjcc.v9.i21.5812
Soluble programmed death-1 is predictive of hepatitis B surface antigen loss in chronic hepatitis B patients after antiviral treatment
Ning Tan, Hao Luo, Qian Kang, Jia-Li Pan, Ran Cheng, Hong-Li Xi, Hong-Yu Chen, Yi-Fan Han, Yu-Ping yang, Xiao-Yuan Xu
Ning Tan, Hao Luo, Qian Kang, Jia-Li Pan, Ran Cheng, Hong-Li Xi, Hong-Yu Chen, Yi-Fan Han, Yu-Ping yang, Xiao-Yuan Xu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
Author contributions: Tan N designed and performed the research, collected and analyzed the data, and wrote the article; Luo H, Pan JL, and Xi HL collected the data and samples; Kang Q and Cheng R collected the data; Chen HY, Yang YQ and Han YF analyzed the data; Xu XY edited, reviewed, and approved the final article.
Supported by The 13th Five-Year Plan of Ministry of Science and Technology of the People’s Republic of China, No. 2017ZX10302201-004-009, and No. 2017ZX10203202-003; and Beijing Municipal Science and Technology Commission of Major Projects, No. D161100002716002, and No. D161100002716003.
Institutional review board statement: The study was approved by the ethics committee of Peking University First Hospital. The study protocol conformed to the ethical guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of Shanghai Jing An District Central Hospital (Approval No. 090f51e6809a26e1 v1.0).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: We declare that no conflict of interest exists.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xiao-Yuan Xu, MD, Chief Physician, Professor, Department of Infectious Diseases, Peking University First Hospital, No. 8 Xishiku Street, Beijing 100034, China.
Received: February 24, 2021
Peer-review started: February 24, 2021
First decision: April 18, 2021
Revised: May 2, 2021
Accepted: May 26, 2021
Article in press: May 26, 2021
Published online: July 26, 2021
Research background

Recent studies analyzed serum soluble programmed death-1 (sPD-1) levels and indicated that sPD-1 might play an important role in virus-specific immunity in chronic viral infection.

Research motivation

The factors that contribute to the functional cure in patients with chronic hepatitis B remain unclear, and the predictors of functional cure are worth exploring.

Research objectives

To investigate the factors associated with hepatitis B surface antigen (HBsAg) loss and explore the impact of sPD-1 Levels.

Research methods

Patients with positive hepatitis B e antigen (HBeAg) levels at baseline and with available sequential samples who achieved HBsAg loss during antiviral treatment served as the case group. This case group (n = 11) was further matched to 44 positive HBeAg patients without HBsAg loss as controls.

Research results

Patients with HBsAg loss had higher levels of sPD-1 than patients without HBsAg loss from baseline to month 96, and the differences were significant between the groups at baseline (P = 0.0136), months 6 (P = 0.0003), 12 (P < 0.0001), 24 (P = 0.0007), 48 (P < 0.0001), and 96 (P = 0.0142). The sPD-1 levels were positively correlated with ALT and HBV DNA levels in patients with HBsAg loss within 12 mo of antiviral treatment. After 12 mo of antiviral treatment, the sPD-1 levels were negatively correlated with HBsAg levels in all patients, especially at 24 (r = -0.356, P = 0.0497) and 48 (r = -0.4783, P = 0.0037) mo. The AUC of sPD-1 levels at 6 mo for HBsAg loss was 0.898 (P = 0.000), whereas that of HBsAg was 0.617 (P = 0.419). The cut-off value of sPD-1 was set at 2.34 log pg/mL; the sensitivity and specificity were 100% and 66.7%, respectively.

Research conclusions

The sPD-1 levels were significantly different between the two groups of patients during antiviral treatment, especially within 12 mo after baseline. The sPD-1 levels at 6 mo can predict HBsAg loss after 144 mo of antiviral treatment.

Research perspectives

The correlation between sPD-1 levels and HBsAg loss depended on the immune response of functional HBV-specific T cells to HBV infection. The T cell function of patients from this study needed to be detected.