Posttransplant Calcineurin Inhibitors Levels and Intrapatient Variability Are Not Associated With Long-term Outcomes Following Liver Transplantation
Bibliographic record
Abstract
BACKGROUND: There is an interest in understanding the association between early calcineurin inhibitors exposure post-liver transplantation (LT) and long-term outcomes. We aimed to analyze this association exploring median calcineurin inhibitor levels and intrapatient variability (IPV) in a multicenter, retrospective cohort. METHODS: Tacrolimus (Tac) and Cyclosporine (CsA) levels obtained during the first 15 days post-LT were collected. High immunosuppression (IS) was considered as a median of Tac, CsA blood trough levels 12 hours after drug administration, or blood levels 2 hours after drug administration higher than 10, 250, or 1200 ng/mL, respectively, or a peak of Tac >20 ng/mL. Optimal IS was defined as a median of Tac, CsA blood trough levels 12 hours after drug administration, or blood levels 2 hours after drug administration levels between 7 and 10, 150 and 250, or 800 and 1200 ng/mL. Low IS was defined as below the thresholds of optimal IS. IPV was estimated during the first 15 days post-LT. RESULTS: The study included 432 patients with a median follow-up of 8.65 years. IS regimen was based on either Tac or CsA in 243 (56.3%) and 189 (43.8%), respectively. There were no differences in terms of graft loss among low versus optimal and high IS groups (P = 0.812 and P = 0.451) nor in high versus low IPV (P = 0.835). Only viral hepatitis and arterial hypertension were independently associated with higher graft loss (hazard ratio = 1.729, P = 0.029 and hazard ratio = 1.570, P = 0.021). CONCLUSIONS: In contrast to what has previously been reported, no association was found between very early postoperative over IS or high IPV and long-term outcome measures following LT. Strategies aimed at reducing these long-term events should likely focus on other factors or on a different IS time window.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 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".