The CD8+ T cell exhaustion mechanisms in chronic hepatitis B infection and immunotherapeutic strategies: a systematic review

ABSTRACT

Introduction

The hepatitis B virus (HBV) continues to be a leading cause of morbidity and mortality worldwide. In developing countries, HBV is the most common etiology of those liver diseases such as chronic hepatitis B (CHB), acute hepatitis B (AHB), acute-on-chronic liver failure (ACLF), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). CD8+ T cell exhaustion is a condition of T cell malfunction and reduction that plays a crucial role in the progression of HBV infection.

Areas covered

This systematic review attempts to evaluate the main inhibitory mechanisms involved in CD8+ T cell exhaustion, in different clinical phases of HBV infection and relation to disease progression. A systematic search in PubMed, Web of Science, and Scopus was performed to identify articles published in English till October 2022.

Expert opinion

According to the numerous conducted studies, we conclude that CD8+ T cell exhaustion commonly occurs in the tumoral and chronic suppressive environment and CHB and HCC patients; furthermore, this phenomenon is less seen in AHB and ACLF patients. The emergence of surficial inhibitory receptors (IRs) on CD8+ T cells is the leading cause of exhaustion, and programmed cell death protein-1 (PD-1) has much importance among the others.

KEYWORDS:

• CD8+ T cell exhaustion
• chronic HBV infection
• hepatitis B virus
• immunotherapy
• inhibitory receptors

Article highlights

• Hepatitis B virus (HBV) continues to be a leading cause of morbidity and mortality in worldwide.

• CD8+ T cell exhaustion commonly occurs in chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients.

• Expression of inhibitory receptors (IRs) is known as the main cause of CD8+ T cell exhaustion.

• PD-1 can be considered as a hallmark of CD8+ T cell exhaustion.

• Restoring the function of CD8+ T cells exhaustion through the removal of inhibitory mechanisms is highly recommended for the treatment of CHB.

Acknowledgments

We acknowledge all supports given by our colleagues at Baqiyatallah university Research Center for Gastroenterology and Liver Diseases (BRCGL) of Baqiyatallah Medical Sciences University (BMSU).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

E Allahmoradi: Conceptualization, Overall design, Writing – original draft. R Mohammadi and P Kheirandish Zarandi: Study quality appraisal, Writing – review & editing. M Heiat and S Alavian: Directed the project, Critical revision of the paper, Writing – review & editing. All authors read and approved the final manuscript for publication.

Additional information

Funding

This paper was not funded.