<scp>HBV</scp> Suppression by Nucleos(t)ide Analogues Reduces <scp>PD</scp> ‐1 Expression on Liver‐Resident T Cells
Bibliographic record
Abstract
ABSTRACT Background and Aim PD‐1‐expressing T cells within the HBV‐infected liver constitute a target of novel immunotherapeutics. Our aim was to investigate the impact of viral suppression on PD‐1 expression on intrahepatic versus circulating lymphocyte populations from chronic hepatitis B (CHB) patients. Methods Twenty‐two CHB patients, nine of them on nucleos(t)ide analogues (NUCs), had paired blood, liver fine needle aspirations (FNAs) and biopsies. A subset had a follow‐up FNA after treatment initiation ( n = 4) or discontinuation ( n = 4). Intrahepatic (iHBV‐DNA and cccDNA) and serum (HBV‐DNA, HBsAg, HBcrAg and cirB‐RNA) viral markers were quantified. Flow cytometry was used for immunophenotyping PBMCs and intrahepatic lymphocytes. An independent liver FNA scRNAseq dataset was used to consolidate our results. Results PD‐1 expression on tissue‐resident memory CD8 T cells (T RM ) correlated with both iHBV‐DNA and cccDNA, as well as surrogate markers of cccDNA transcriptional activity (cirB‐RNA and HBcrAg) in CHB patients with mild hepatitis. These associations were not reflected in circulating T cells. PD‐1 expression intensity on CD8 T RM was lower in NUC‐treated than in naive patients, changes that were again not detectable in the circulation. Longitudinal analysis showed that viral load rebound induced by NUC discontinuation had the potential to drive re‐expression of high levels of PD‐1 on CD8 T RM . Conversely, therapy initiation and subsequent viral suppression reversed these changes. scRNAseq results further extended the profiling of these PD‐1 + CD8 T RM , showing a phenotype consistent with bystander activation in response to subclinical liver damage. Conclusions Intrahepatic viral markers correlate with PD‐1 expression on global liver‐resident T cells of CHB patients with mild hepatitis, with a reduction after prolonged NUC therapy and re‐expression following treatment withdrawal.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".