EVALUATION OF THE EFFECT OT IMMUNOSUPPRESSIVE AGENTS ON HEPATITIS C
Bibliographic record
Abstract
O35 Aims: Hepatitis C virus (HCV) infection is the leading indication for liver transplantation. HCV recurrence is universal and can lead to graft loss. Clinical studies suggest that the type and intensity of immunosuppression can significantly influence the evolution of this infection. Despite the risk of increased rejection, the current trend in the management of these patients is to lower immunosuppression in order to reduce viral replication. We hypothesized that the different immunosuppressive drugs didn’t have the same effect on HCV replication. The aim of our study was to evaluate HCV replication in the HUH-7 cell line carrying the subgenomic HCV replicon with or without exposure to non toxic concentrations of the different immunosuppressive agents currently used in liver transplantation. Methods: HCV replication was evaluated by measuring genomic RNA by real time PCR and viral protein expression by western blotting. Cell proliferation was evaluated by measuring [3H]-thymidine incorporation in DNA. Results: Thymidine incorporation was similar in cells exposed to tacrolimus, hydrocortisone, interferon and control, and slightly reduced in cells exposed to cyclosporin and rapamycin (respectively 87% and 75% of control, p<0.05). Mycophenolate mofetyl (MMF) dramatically reduced thymidine incorporation in these cells (2% of control, p<0.01). As expected, interferon-α (500UI/mL) significantly reduced the number of positive strand RNA by 1.76 log after 48 hours of exposure (p<0.03), the level of expression of the non-structural protein NS5a (39% of control, p<0.03) and the amount of negative strand HCV RNA (43% of control, p<0.03). Rapamycin (10 nM), tacrolimus (250 nM) and hydrocortisone (250 μM) did not significantly modify HCV replication. On the other hand, MMF (10 μg/ml) reduced the amount of positive strand by 1.09 log (p<0.01) and the level of NS5a expression (46% of control, p<0.01). Cyclosporin (2.5μg/ml) also reduced the amount of positive strand by 1.85 log (p<0.01), the level of NS5a expression (46% of control, p<0.05) and the amount of HCV RNA negative strand (66% of control, p<0.05). Verapamil and quinine, which are P-glycoprotein blockers such as cyclosporin also had the capacity to reduce HCV replication. Conclusions: These results suggest that immunosuppressive agents can significantly modify HCV replication in the replicon model and that the response differs depending on the type of agents. Since HCV replication is affected by cell proliferation in the replicon model and that MMF significantly affected this parameter, cyclosporin is the only agent that actually decreases HCV replication in our study.
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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 | 0.000 |
| 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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".