Title
The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study
Language
English
Description (en)
Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p< 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p< 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p< 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p< 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.
Keywords (en)
Reactive Oxygen; Surgery; Pathophysiology; Failure; Injury; Risk
DOI
10.3390/antiox13050590
Author of the digital object
Florian  Primavesi  (Medical University of Innsbruck)
Jakob  Troppmair  (Medical University of Innsbruck)
Stefan  Stättner  (Salzkammergutklinikum)
Dietmar  Öfner  (Medical University of Innsbruck)
Daniel  Neureiter  (Paracelsus Medical University)
Stefan  Schneeberger  (Medical University of Innsbruck)
Herbert  Tilg  (Medical University of Innsbruck)
Eckhard  Klieser  (Paracelsus Medical University)
Silvia  Gasteiger  (Medical University of Innsbruck)
Thomas  Niederwieser  (Medical University of Innsbruck)
Benno  Cardini  (Medical University of Innsbruck)
Manuel  Maglione  (Medical University of Innsbruck)
Thomas  Resch  (Medical University of Innsbruck)
Rupert  Oberhuber  (Medical University of Innsbruck)
Eva  Braunwarth  (Medical University of Innsbruck)
Markus  Anliker  (Medical University of Innsbruck)
Bettina  Neumayer  (Paracelsus Medical University)
Silvia  Eller  (Medical University of Innsbruck)
Georg  Csukovich  (University of Veterinary Medicine Vienna / Medical University of Innsbruck)
Pietro  Di Fazio  (Philipps-Universität Marburg)
Aleksandar  Nikolajevic  (Medical University of Innsbruck)
Thomas  Senoner  (Medical University of Innsbruck)
Sophie  Schindler  (Medical University of Innsbruck)
Format
application/pdf
Size
1.3 MB
Licence Selected
CC BY 4.0 International
Type of publication
Article
Name of Publication (en)
Antioxidants
Pages or Volume
19
Volume
13
Number
5
Publisher
MDPI
Publication Date
2024
Content
Details
Object type
PDFDocument
Format
application/pdf
Created
10.06.2024 09:22:35
This object is in collection
Metadata
Veterinärmedizinische Universität Wien (Vetmeduni) | Veterinärplatz 1 | 1210 Wien - Österreich | T +43 1 25077-0 | Web: vetmeduni.ac.at