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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Yuan Xu, MD, Chief Physician, Professor, Department of Infectious Diseases, Peking University First Hospital, No. 8 Xishiku Street, Beijing 100034, China. xiaoyuanxu6@163.com
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
Processing time: 146 Days and 23.7 Hours
Abstract
BACKGROUND

Hepatitis B surface antigen (HBsAg) loss, a functional cure in patients with chronic hepatitis B (CHB) undergoing antiviral therapy, might be an ideal endpoint of antiviral treatment in clinical practice. The factors that contribute to the functional cure remain unclear, and the predictors of functional cure are worth exploring. The concentration and kinetics of soluble programmed death-1 (sPD-1) in patients with CHB may play an important role in elucidating the immune response associated with functional cure after nucleos(t)ide analogs therapy.

AIM

To investigate the factors associated with HBsAg loss and explore the influence of sPD-1 Levels.

METHODS

This study analyzed the data and samples from patients with CHB who underwent antiviral treatment in a non-interventional observational study conducted at Peking University First Hospital in Beijing (between 2007 and 2019). All patients were followed up: Serum samples were collected every 3 mo during the first year of antiviral treatment and every 6 mo thereafter. Patients with positive hepatitis B e antigen 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 hepatitis B e anti patients without HBsAg loss as controls. The Spearman’s rank correlation test and receiver operating characteristic curves analysis were performed.

RESULTS

The sPD-1 Levels were higher in patients with HBsAg loss than in those 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). After 6 mo of antiviral treatment, the sPD-1 levels were positively correlated with alanine transaminase (ALT) levels (r = 0.5103, P = 0.0017), and the sPD-1 levels showed apparent correlation with ALT (r = 0.6883, P = 0.0192) and HBV DNA (r = 0.5601, P = 0.0703) levels in patients with HBsAg loss. After 12 mo of antiviral treatment, the sPD-1 levels also showed apparent correlation with ALT (r = 0.8134, P = 0.0042) and HBV DNA (r = 0.6832, P = 0.0205) levels in patients with HBsAg loss. The sPD-1 levels were negatively correlated with HBsAg levels in all patients after 12 mo of antiviral treatment, especially at 24 (r = -0.356, P = 0.0497) and 48 (r = -0.4783, P = 0.0037) mo. After 6 mo of antiviral treatment, the AUC of sPD-1 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.

CONCLUSION

The sPD-1 levels at 6 mo can predict HBsAg loss after 144 mo of antiviral treatment.

Keywords: Programmed cell death 1 protein; Hepatitis B surface antigen; Chronic hepatitis B; Antiviral; Nucleos(t)ide analogs; Hepatitis B e antigen

Core Tip: This study analyzed the data and samples from patients with chronic hepatitis B who underwent antiviral treatment and were followed up for 12 years to investigate the factors associated with hepatitis B surface antigen (HBsAg) loss and explore the impact of soluble programmed death-1 (sPD-1) levels. The sPD-1 levels were significantly different between patients with and without HBsAg loss during antiviral treatment. The sPD-1 levels at 6 mo can predict HBsAg loss after 12 years of antiviral treatment.