Dataset Information

Model to predict on-treatment restoration of functional HBV-specific CD8⁺ cell response foresees off-treatment HBV control in eAg-negative chronic hepatitis B.

ABSTRACT:

Background

Hepatitis B virus (HBV)-specific CD8⁺ cell response restoration during nucleos(t)ide analogue (NUC) treatment could lead to off-treatment HBV control in e-antigen-negative chronic hepatitis B (CHBe(-)).

Aim

To predict this response with variables involved in T-cell exhaustion for use as a treatment stopping tool.

Methods

In NUC-treated CHBe(-) patients, we considered a functional response in cases with HBV-specific CD8⁺ cells against core and polymerase HBV epitopes able to proliferate and secrete type I cytokines after antigen encounter. We performed a logistic regression model (LRM) to predict the likelihood of developing this response, based on patient age (subrogate of infection length), HBsAg level, NUC therapy starting point and duration (antigenic pressure). We discontinued treatment and assessed HBV DNA dynamics, HBsAg decline and loss during off-treatment follow-up according to LRM likelihood.

Results

We developed an LRM that predicted the presence of a proliferative type I cytokine-secreting CD8⁺ cell response, which correlated positively with treatment duration and negatively with treatment initiation after the age of 40 years and with age adjusted by HBsAg level. We observed a positive correlation between LRM probability and intensity of proliferation, number of epitopes with the functional proliferating response and type I cytokine secretion level. Off-treatment, HBsAg loss, HBsAg decline >50% and HBV control were more frequent in the group with >90% LRM probability.

Conclusions

Short-term low-level antigen exposure and early long-term NUC treatment influence the restoration of a functional HBV-specific CD8⁺ cell response. Based on these predictors, a high likelihood of detecting this response at treatment withdrawal is associated with off-treatment HBV control and HBsAg decline and loss.

SUBMITTER: Pena-Asensio J

PROVIDER: S-EPMC9305412 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background & aimsCD161-expressing CD8+ T cells consist of mucosal-associated invariant T cells with semi-invariant T-cell receptor (TCR) use and non-mucosal-associated invariant T CD161+CD8+ T cells with polyclonal TCR repertoire. Although CD161+CD8+ T cells are enriched in liver and embrace hepatitis B virus (HBV)-specific T cells in chronic hepatitis B (CHB) patients, their roles in disease progression remain poorly understood. This study aimed to decipher their profiling and dynamic changes during chronic HBV infection.MethodsBlood samples from 257 CHB patients and nontumor liver specimens from 73 HBV-positive patients were analyzed for CD161+CD8+ T-cell characterization by flow cytometry, TCR repertoire determination, transcriptomic analyses, and cell experiments.ResultsCD161+CD8+ T cells were increased and hyperactivated in patients, while positive correlation between the CD161+CD8+ T-cell ratio and HBV-DNA level suggested this was insufficient to control HBV replication. The overlap of complementarity determining region 3 sequences supported the switch between CD161-CD8+ and CD161+CD8+ populations. Although CD161+CD8+ T cells were endowed with innateness phenotype and enhanced antiviral capacity, the population from patients had impaired type I cytokine production, and increased interleukin 17 and granzyme B secretion. The increased CD161+CD8+ T cells and their increased granzyme B secretion correlated positively with inflammation-associated liver injury. Hepatic CD161+CD8+ T cells showed neutrophil-related pathogenic potential because they had increased transcript signatures and proinflammatory cytokine production in neutrophil recruitment- and response-related pathways that changed consistently in the injured liver.ConclusionsOur results highlight the reduced antiviral potency but increased pathogenic potential of CD161+CD8+ T cells in CHB patients, supporting CD161 expression as a marker of pathogenic CD8+ T subset and the intervention target for liver injury.

Dataset Information

Model to predict on-treatment restoration of functional HBV-specific CD8⁺ cell response foresees off-treatment HBV control in eAg-negative chronic hepatitis B.

Background

Aim

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Model to predict on-treatment restoration of functional HBV-specific CD8+ cell response foresees off-treatment HBV control in eAg-negative chronic hepatitis B.

Background

Aim

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Model to predict on-treatment restoration of functional HBV-specific CD8⁺ cell response foresees off-treatment HBV control in eAg-negative chronic hepatitis B.