A29 THE MOLECULAR INTERPLAY BETWEEN CIRCULATING MIR-24, MIR-223, AND PCSK9 IN HEPATITIS C-INFECTED PATIENTS WHO ACHIEVE A TREATMENT-BASED VIRAL CURE
Bibliographic record
Abstract
Hepatitis C virus (HCV) hijacks host lipid metabolic pathways as part of its replication cycle. Chronic HCV infection is associated with altered metabolism, which both contributes to disease progression and influences response to therapy. To help understand how HCV influences important metabolic pathways of chronic liver disease, we investigated the molecular interplay between four circulating regulators of lipid homeostasis (miR-122, miR-24, miR-223 and proprotein convertase subtilisin/kexin type 9 (PCSK9)) in HCV-infected patients who achieved viral cure with interferon-based treatment. Circulating plasma levels of microRNAs were measured at multiple time-points during antiviral therapy in individuals achieving sustained virologic response (SVR) (n=57), relapsers (n=10), and non-responders (n=27). The concentration of plasma PCSK9 was assessed in paired samples before and after treatment in SVR (n=27) and relapsers (n=7). We report that miR-24 and miR-223 levels were significantly increased in HCV-infected patients who achieve SVR (miR-24, p-value < 0.0001; miR-223, p-value < 0.0001). In contrast, miR-122 decreased after HCV clearance (p-value < 0.0001), correlating with normalized liver-specific enzymes. Quantitative correlation between amounts of circulating miR-24 and miR-223 was also observed (r=0.91, p-value ≤ 0.0001) for all patients. Importantly, plasma PCSK9 concentrations were significantly upregulated in HCV-infected patients who achieve SVR (p-value=0.002). Also, miR-24 and PCSK9 levels were correlated (r=0.24, p-value ≤ 0.02) in HCV-infected patients, indicating for the first time an in vivo link between the two. A modulatory effect of PCSK9 on HCV infection was demonstrated using a cell-based system of viral infection employing recombinant human wild-type PCSK9 and PCSK9 gain- and loss-of-function mutants. Together, these results provide the first insights into a novel coordinated interplay between three important molecular players in lipid homeostasis—lipoprotein-associated miR-24 and miR-223 and circulating PCSK9— whose regulation are affected by HCV infection and treatment-based viral cure. Canadian Network on Hepatitis C
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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 source (direct Gemma or distilled Codex), 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".