Dataset Information

Possibility of PD-1/PD-L1 Inhibitors for the Treatment of Patients with Chronic Hepatitis B Infection.

ABSTRACT:

Background

Chronic hepatitis B (CHB) infection is still a major global public health problem, with nearly two billion patients. Although current antiviral drugs can inhibit viral replication and reduce hepatitis B virus (HBV) related complications, it is difficult to achieve clinical endpoints due to drug resistance.

Summary

Immune checkpoint inhibitors (ICIs) are an important strategy to reverse T-cell exhaustion, and rebuilding an effective functional T-cell response is a promising immunomodulatory approach for CHB patients. However, ICIs may lead to viral reactivation or immune-related adverse effects. There are still many controversies in the application of ICIs in treating patients with CHB.

Key messages

This article reviews the research progress of ICIs in CHB infection and related issues. The goal of this paper was to summarize the possible impact of new therapies for CHB with the aim of reducing potential clinical risks.

SUBMITTER: Su M

PROVIDER: S-EPMC10836741 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Possibility of PD-1/PD-L1 Inhibitors for the Treatment of Patients with Chronic Hepatitis B Infection.

Su Menghan M Ye Ting T Wu Wei W Shu Zheyue Z Xia Qi Q

Digestive diseases (Basel, Switzerland) 20231011 1

<h4>Background</h4>Chronic hepatitis B (CHB) infection is still a major global public health problem, with nearly two billion patients. Although current antiviral drugs can inhibit viral replication and reduce hepatitis B virus (HBV) related complications, it is difficult to achieve clinical endpoints due to drug resistance.<h4>Summary</h4>Immune checkpoint inhibitors (ICIs) are an important strategy to reverse T-cell exhaustion, and rebuilding an effective functional T-cell response is a promis ...[more]

PMID: 37820605

Similar Datasets

Project description:Background & aimsCurrent therapies for chronic hepatitis B virus (HBV) infection control viral replication but do not eliminate the risk of progression to hepatocellular carcinoma. HBV-specific CD8 T cells are necessary for viral control, but they are rare and exhausted during chronic infection. Preclinical studies have shown that blockade of the PD-1:PD-L1 axis can restore HBV-specific T cell functionality. The aim of this study was to analyze how the clinical and treatment status of patients impacts the ability of HBV-specific T cells to respond to PD-L1 blockade.MethodsExpression patterns of the PD-1:PD-L1/PD-L2 axis were analyzed in healthy donors and chronically infected patients in different clinical phases of disease. A functional assay was performed to quantify baseline HBV-specific T cell responses in chronically infected patients. Baseline responses were then compared to those attained in the presence of an anti-PD-L1 monoclonal antibody (MEDI2790).ResultsChronically infected patients were characterized by the upregulation of PD-1 within the T cell compartment and a concomitant upregulation of PD-L1 on myeloid dendritic cells. The upregulation was maximal in HBV e antigen (HBeAg)-positive patients but persisted after HBeAg negativization and was not restored by long-term treatment. HBV reactivity, measured as frequency of HBV-specific T cells, was significantly higher in HBeAg-negative patients with lower HBV DNA levels, independently of HBV surface antigen or alanine aminotransferase levels. Anti-PD-L1 blockade with MEDI2790 increased both the number of IFN-γ-producing T cells and the amount of IFN-γ produced per cell in 97% of patients with detectable HBV reactivity, independently of patients' clinical or treatment status.ConclusionPatients with lower levels of HBV DNA and the absence of HBeAg have more intact HBV-specific T cell immunity and may benefit the most from PD-L1 blockade as a monotherapy.Lay summaryHepatitis B virus (HBV)-specific T cell responses during chronic infection are weak due to the upregulation of inhibitor molecules on the immune cells. In this study we show that the inhibitory PD-1:PD-L1 axis is upregulated during chronic HBV infection and successful antiretroviral therapy does not restore normal levels of PD-1 and PD-L1 expression. However, in HBV e antigen-negative patients, treatment with an anti-PD-L1 antibody can increase the functionality of HBV-specific T cell responses by an average of 2-fold and is a promising new therapy for patients with chronic HBV infection.

Dataset Information

Possibility of PD-1/PD-L1 Inhibitors for the Treatment of Patients with Chronic Hepatitis B Infection.

Background

Summary

Key messages

Publications

Possibility of PD-1/PD-L1 Inhibitors for the Treatment of Patients with Chronic Hepatitis B Infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets