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

Expert Rev Clin Immunol. 2023 Jun;19(6):671-688. doi: 10.1080/1744666X.2023.2198209. Epub 2023 Apr 13.

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.

Publication types

  • Systematic Review

MeSH terms

  • CD8-Positive T-Lymphocytes / pathology
  • Carcinoma, Hepatocellular* / therapy
  • Hepatitis B virus / physiology
  • Hepatitis B* / metabolism
  • Hepatitis B* / pathology
  • Hepatitis B, Chronic* / pathology
  • Hepatitis B, Chronic* / therapy
  • Humans
  • Immunotherapy
  • Liver Neoplasms* / therapy
  • T-Cell Exhaustion