Soluble Programmed Cell Death-1 is a Novel Predictor of HBsAg Loss in Chronic Hepatitis B Patients When Long-Term Nucleos(t)ide Analog Treatment is Discontinued

Guichan Liao; Ziying Liu; Muye Xia; Hongjie Chen; Houji Wu; Bing Li; Tao Yu; Shaohang Cai; Xiaoyong Zhang; Jie Peng

doi:10.2147/IDR.S360202

Soluble Programmed Cell Death-1 is a Novel Predictor of HBsAg Loss in Chronic Hepatitis B Patients When Long-Term Nucleos(t)ide Analog Treatment is Discontinued

Infect Drug Resist. 2022 Apr 29:15:2347-2357. doi: 10.2147/IDR.S360202. eCollection 2022.

Authors

Guichan Liao¹, Ziying Liu¹, Muye Xia¹, Hongjie Chen¹, Houji Wu¹, Bing Li¹, Tao Yu¹, Shaohang Cai¹, Xiaoyong Zhang¹, Jie Peng¹

Affiliation

¹ State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Abstract

Purpose: The immunoinhibitory receptor, programmed death 1 (PD-1), plays a critical role in immune suppression during chronic viral infection. The significance of circulating soluble PD-1 (sPD-1) in patients with chronic hepatitis B who have discontinued long-term nucleos(t)ide analog (NA) treatment remains unknown.

Patients and methods: A prospective cohort study was conducted using serial blood samples from chronic hepatitis B patients who discontinued long-term NA treatment. The current analysis included 115 non-cirrhotic patients with HBV DNA negative and HBsAg positive at the moment of NA discontinuation. Levels of sPD-1 were measured in all available samples using sandwich enzyme-linked immunoassay.

Results: Sixty-two patients experienced a clinical relapse and 14 occurred HBsAg loss, with 8-year cumulative rates of 56.6% and 23.4%, respectively. Time-dependent receiver operating characteristic curve analysis for sPD-1 derived 156 pg/mL, which is equivalent to the detectable threshold, as an optimal cut-off value for predicting 8-year clinical relapse. Patients with detectable sPD-1 at end of treatment (EOT) had a significant lower incidence of clinical relapse (48% vs 67%, hazard ratio [HR] 0.454, p = 0.006), but a remarkable higher probability of HBsAg loss (33.7% vs 2.4%, HR 9.17, p = 0.038), compared to those who with undetectable sPD-1, respectively.

Conclusion: EOT sPD-1 levels predicted clinical relapse and HBsAg loss after treatment discontinuation and may help to guide a finite NA treatment plan for patients with chronic hepatitis B virus infection.

Keywords: chronic hepatitis B; discontinuation; nucleos(t)ide analogs; programmed cell death 1 protein.

Grants and funding

This study was supported by grants from the National Science Foundation of China (No.81971949, No.86878446), Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (No.LC2016PY003) and Clinical Research Program of Nanfang Hospital, Southern Medical University (No.2018CR026). The funding sources did not have any influence on the study design, data collection, analysis and interpretation of the data, writing of the manuscript, or decision to submit for publication.