The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study
Florian Primavesi,
Thomas Senoner,
Sophie Schindler,
Aleksandar Nikolajevic,
Pietro Di Fazio,
Georg Csukovich,
Silvia Eller,
Bettina Neumayer,
Markus Anliker,
Eva Braunwarth,
Rupert Oberhuber,
Thomas Resch,
Manuel Maglione,
Benno Cardini,
Thomas Niederwieser,
Silvia Gasteiger,
Eckhard Klieser,
Herbert Tilg,
Stefan Schneeberger,
Daniel Neureiter,
Dietmar Öfner,
Jakob Troppmair,
Stefan Stättner
Affiliations
Florian Primavesi
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Thomas Senoner
Department of Anaesthesiology and Intensive Care Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria
Sophie Schindler
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Aleksandar Nikolajevic
Daniel Swarovski Research Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Pietro Di Fazio
Department of Visceral, Thoracic and Vascular Surgery, Philipps-Universität Marburg, 35043 Marburg, Germany
Georg Csukovich
Daniel Swarovski Research Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Silvia Eller
Daniel Swarovski Research Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Bettina Neumayer
Institute of Pathology, Paracelsus Medical University/University Hospital Salzburg (SALK), 5020 Salzburg, Austria
Markus Anliker
Central Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Innsbruck, 6020 Innsbruck, Austria
Eva Braunwarth
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Rupert Oberhuber
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Thomas Resch
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Manuel Maglione
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Benno Cardini
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Thomas Niederwieser
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Silvia Gasteiger
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Eckhard Klieser
Institute of Pathology, Paracelsus Medical University/University Hospital Salzburg (SALK), 5020 Salzburg, Austria
Herbert Tilg
Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, 6020 Innsbruck, Austria
Stefan Schneeberger
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Daniel Neureiter
Institute of Pathology, Paracelsus Medical University/University Hospital Salzburg (SALK), 5020 Salzburg, Austria
Dietmar Öfner
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Jakob Troppmair
Daniel Swarovski Research Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Stefan Stättner
Department of General, Visceral and Vascular Surgery, Salzkammergutklinikum, 4840 Vöcklabruck, Austria
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 p p p 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.
