HBV Suppression by Nucleos(t)ide Analogues Reduces PD-1 Expression on Liver-Resident T Cells

Area of Science:

• Immunology
• Hepatology
• Virology

Background:

• Programmed cell death protein 1 (PD-1) expressing T cells in the liver are a target for hepatitis B virus (HBV) immunotherapies.
• Chronic hepatitis B (CHB) patients exhibit distinct PD-1 expression patterns in intrahepatic versus circulating lymphocytes.

Purpose of the Study:

• To investigate the impact of viral suppression on PD-1 expression in intrahepatic and circulating lymphocytes of CHB patients.
• To explore the relationship between intrahepatic viral markers and PD-1 expression on liver-resident T cells.

Main Methods:

• Paired blood and liver fine needle aspirates (FNAs) were analyzed from 22 CHB patients, including 9 on nucleos(t)ide analogues (NUCs).
• Intrahepatic and serum viral markers were quantified; flow cytometry assessed lymphocyte populations.
• scRNAseq data from an independent liver FNA cohort validated findings.

Main Results:

• PD-1 expression on intrahepatic CD8 T resident memory cells (T_RM) correlated with intrahepatic HBV DNA (iHBV-DNA), cccDNA, and viral transcriptional markers (cirB-RNA, HBcrAg) in mild hepatitis.
• NUC treatment reduced PD-1 expression on CD8 T_RM, a change not seen in circulating T cells.
• NUC discontinuation led to PD-1 re-expression on CD8 T_RM, while therapy initiation reversed this.

Conclusions:

• Intrahepatic viral markers are linked to PD-1 expression on liver-resident T cells in CHB patients with mild hepatitis.
• Prolonged NUC therapy reduces PD-1 expression, which is re-expressed upon treatment withdrawal, indicating a dynamic immune response.