Is there a Role for Cyclophilin Inhibitors in the Management of Primary Biliary Cirrhosis?
Bibliographic record
Abstract
Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are poorly understood autoimmune liver diseases. Immunosuppression is used to treat AIH and ursodeoxycholic acid is used to slow the progression of PBC. Nevertheless, a proportion of patients with both disorders progress to liver failure. Following liver transplantation, up to a third of patients with PBC experience recurrent disease. Moreover a syndrome referred to as "de novo AIH" occurs in a proportion of patients regardless of maintenance immunosuppression, who have been transplanted for disorders unrelated to AIH. Of note, the use of cyclosporine A appears to protect against the development of recurrent PBC and de novo AIH even though it is a less potent immunosuppressive compared to tacrolimus. The reason why cyclosporine A is protective has not been determined. However, a virus resembling mouse mammary tumor virus (MMTV) has been characterized in patients with PBC and AIH. Accordingly, we hypothesized that the protective effect of cyclosporine A in liver transplant recipients may be mediated by the antiviral activity of this cyclophilin inhibitor. Treatment of the MMTV producing MM5MT cells with different antivirals and immunosuppressive agents showed that both cyclosporine A and the analogue NIM811 inhibited MMTV production from the producer cells. Herein, we discuss the evidence supporting the role of MMTV-like human betaretrovirus in the development of PBC and de novo AIH and speculate on the possibility that the agent may be associated with disease following transplantation. We also review the mechanisms of how both cyclosporine A and NIM811 may inhibit betaretrovirus production in vitro.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".