Intermittent Subnormothermic Ex Vivo Liver Perfusion Reduces Endothelia Cell Death and Decreases Bile Duct Injury After Pig Liver Transplantation With DCD Grafts.
Bibliographic record
Abstract
Ischemic-type biliary lesions (ITBL) are the main obstacle for liver transplantation using organ donation after cardiac death (DCD). We developed a novel technique of subnormothermic ex vivo liver perfusion (SNEVLP) for the preservation of liver grafts suitable for a clinical setting. Methods: In a porcine DCD transplant model (45min warm ischemia time), liver grafts were either stored for 10hr at 4°C (CS, n=5) or preserved combining a total of 7hr cold storage and 3hr SNEVLP (33°C, n=5). Combination of cold storage and SNELP was used to simulate a clinical relevant scenario including graft transportation on ice and organ cooling for graft implantation. Parameters of hepatocyte (AST, INR), endothelial cell (Hyaluronic Acid, CD31 immunohistochemistry), Kupffer cell (β-Galactosidase), and biliary (alk. Phosphatase, Bilirubin) injury and function were determined. 5 day animal survival was assessed. Results: 5 day animal survival was similar between the CS and SNEVLP treated groups (40% vs 80%, p=0.8). No difference was observed between CS and SNEVLP groups regarding maximum INR (1.7 vs 2, p=0.9) or maximum AST within 48hr (2500±1100 U/L vs 3010±1530 U/L, p=0.3). In contrast, 7hr after reperfusion the CS vs SNEVLP group showed 5-fold higher Hyaluronic Acid levels (4195±2990 ng/mL vs 737±450 ng/mL, p=0.01) as a marker of endothelial cell damage, and 2-fold increased β-Galactosidase levels (166±17 U/mL vs 95±25 U/ml, p<0.01) reflecting increased Kupffer cell activation. CD31 staining of parenchymal biopsies at 8hr after reperfusion demonstrated massive endothelial cell injury in the CS group while endothelial cells were protected in SNEVLP livers. 3 days after transplantation CS vs SNEVLP groups had higher alk. Phosphatase (179±9 μmol/L vs 80±21 μmol/L, p≤0.05) and Bilirubin levels (20±22 μmol/L vs 6±2 μmol/L) as markers of biliary injury. Bile duct histology at the end of animal survival revealed severe bile duct necrosis in 3 out of 5 animals with CS, while no bile duct injury was observed in SNEVLP treated animals (p=0.026). Conclusion: SNEVLP preservation of DCD grafts reduces bile duct and endothelial cell injury in DCD grafts following liver transplantation. Intermitted SNEVLP preservation is a novel strategy to prevent ITBL in DCD liver grafts with extended warm ischemia times.
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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 | 0.001 |
| 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".