Bile formation in long-term ex situ perfused livers
| Autor: | Philipp Rudolf von Rohr, Dilmurodjon Eshmuminov, Stephanie Häusler, Max Hefti, Matteo Mueller, Dustin Becker, Bruno Stieger, Pierre-Alain Clavien, Julia Steiger, Lucia Bautista Borrego, Martin J. Schuler, Philipp Dutkowski, Catherine Hagedorn, Mark W. Tibbitt |
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| Přispěvatelé: | University of Zurich, Clavien, Pierre-Alain |
| Rok vydání: | 2021 |
| Předmět: |
Swine
Biopsy medicine.medical_treatment 610 Medicine & health Stimulation In Vitro Techniques 030230 surgery Pharmacology Liver transplantation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Bolus (medicine) Liver Function Tests Animals Bile Humans Medicine 10217 Clinic for Visceral and Transplantation Surgery medicine.diagnostic_test business.industry Graft Survival Taurocholic acid Ursodeoxycholic acid 2746 Surgery Liver Transplantation Perfusion Liver chemistry 10199 Clinic for Clinical Pharmacology and Toxicology 030220 oncology & carcinogenesis Models Animal Female Surgery Liver function business Liver function tests Biomarkers medicine.drug |
| Zdroj: | Surgery. 169:894-902 |
| ISSN: | 0039-6060 |
| DOI: | 10.1016/j.surg.2020.11.042 |
| Popis: | Long-term ex situ liver perfusion may rescue injured grafts. Little is known about bile flow during long-term perfusion. We report the development of a bile stimulation protocol and motivate bile flow as a viability marker during long-term ex situ liver perfusion.Porcine and human livers were perfused with blood at close to physiologic conditions. Our perfusion protocol was established during phase 1 with porcine livers (n = 23). Taurocholic acid was applied to stimulate bile flow. The addition of piperacillin-tazobactam (tazobac) and methylprednisolone was modified from daily bolus to controlled continuous application. We adapted the protocol to human livers (n = 12) during phase 2. Taurocholic acid was replaced with medical grade ursodeoxycholic acid.Phase 2: Despite administering taurocholic acid, bile flow declined from 29.3 ± 6.5 to 9.3 ± 1.4 mL/h (P.001). Shortly after bolus of tazobac/methylprednisolone, bile flow recovered to 39.0 ± 9.7 mL/h with a decrease of solid bile components. This implied bile salt independent bile flow stimulation by tazobac/methylprednisolone. Phase 2: Ursodeoxycholic acid was shown to stimulate bile flow ex situ in human livers. Eight livers were perfused successfully for 1 week with continuous bile flow. The other 4 livers demonstrated progressive cell death, of which only 1 exhibited bile flow.A lack of bile flow stimulation leads to a decline in bile flow and is not necessarily a sign of deterioration in liver function. Proper administration of stimulators can induce constant bile flow during ex situ liver perfusion for up to 1 week. Medical grade ursodeoxycholic acid is a suitable replacement for nonmedical grade taurocholic acid. The presence of bile flow alone is not sufficient to assess liver viability. |
| Databáze: | OpenAIRE |
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