The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study
Open accessAbstract
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.
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Postoperative liver function mainly determines the overall course and subsequent morbidity after major hepatectomy.
“Especially in major hepatectomies, the postoperative liver function mainly determines the overall course and subsequent morbidity [7,13,35].”
From The Role of Perioperative Interleukin-6 Serum Levels on Liver Dysfunction and Infectious Complications After Hepatectomy—A Systematic Review (2025) · cites this paper as [35]
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Cites
Rahbari, N. N., Garden, O. J., Padbury, R., Brooke-Smith, M., Crawford, M., Adam, R., Koch, M., Makuuchi, M., Dematteo, R. P., Christophi, C., et al. (2011) · Surgery · doi:10.1016/j.surg.2010.10.001 · Cited by 2,319 · see citing works
Oxidative stress as a crucial factor in liver diseases
Cichoż‐Lach, H. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i25.8082 · Cited by 1,226 · see citing works
DETRE, S. I., Jotti, G. S., & Dowsett, M. (1995) · Journal of Clinical Pathology · doi:10.1136/jcp.48.9.876 · Cited by 884 · see citing works
Management of post-hepatectomy complications
Jin, S. (2013) · World Journal of Gastroenterology · doi:10.3748/wjg.v19.i44.7983 · Cited by 275 · see citing works
Systematic review and meta-analysis of steatosis as a risk factor in major hepatic resection
de Meijer, V. E., Kalish, B. T., Puder, M., & IJzermans, J. N. M. (2010) · British journal of surgery · doi:10.1002/bjs.7194 · Cited by 275 · see citing works
Oxidative Stress and Inflammation: Essential Partners in Alcoholic Liver Disease
Ambade, A., & Mandrekar, P. (2012) · International Journal of Hepatology · doi:10.1155/2012/853175 · Cited by 249 · see citing works
4-Hydroxynonenal in the Pathogenesis and Progression of Human Diseases
Shoeb, M., Ansari, N., Srivastava, S., & Ramana, K. (2013) · Current Medicinal Chemistry · doi:10.2174/09298673113209990181 · Cited by 230 · see citing works
Post hepatectomy liver failure (PHLF) – Recent advances in prevention and clinical management
Søreide, J. A., & Deshpande, R. (2020) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2020.09.001 · Cited by 226 · see citing works
Physiological role of reactive oxygen species as promoters of natural defenses
Roy, J., Galano, J., Durand, T., Guennec, J. L., & Lee, J. C. (2017) · The FASEB Journal · doi:10.1096/fj.201700170r · Cited by 223 · see citing works
A standard definition of major hepatectomy: resection of four or more liver segments
Reddy, S. K., Barbas, A. S., Turley, R. S., Steel, J. L., Tsung, A., Marsh, J. W., Geller, D. A., & Clary, B. M. (2011) · HPB · doi:10.1111/j.1477-2574.2011.00330.x · Cited by 201 · see citing works
Overview of lipid peroxidation products and hepatic protein modification in alcoholic liver disease
McCullough, R. L., Galligan, J. J., Stewart, B. J., & Petersen, D. R. (2011) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2011.02.021 · Cited by 154 · see citing works
Reactive oxygen and nitrogen species in normal physiological processes
Pourová, J., Kottová, M., Vopršalová, M., & Pour, M. (2009) · Acta Physiologica · doi:10.1111/j.1748-1716.2009.02039.x · Cited by 146 · see citing works
Ucar, F., Sezer, S., Erdogan, S., Akyol, S., Armutcu, F., & Akyol, O. (2013) · Redox Report · doi:10.1179/1351000213y.0000000050 · Cited by 143 · see citing works
Post-hepatectomy liver failure.
Kauffmann, R. M., & Fong, Y. (2014) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2304-3881.2014.09.01 · Cited by 140 · see citing works
Reiniers, M. J., van Golen, R. F., van Gulik, T. M., & Heger, M. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5486 · Cited by 131 · see citing works
BOTEON, Y. L., Laing, R. W., Schlegel, A. A., Wallace, L. M., Smith, A. J., Attard, J. A., Bhogal, R. H., Neil, D., Hübscher, S. G., Perera, M. T. P. R., et al. (2018) · Liver Transplantation · doi:10.1002/lt.25315 · Cited by 125 · see citing works
Oxidative stress in surgery in an ageing population: Pathophysiology and therapy
Rosenfeldt, F., Wilson, M. D., Lee, G., Kure, C., Ou, R., Braun, L. A., & de Haan, J. B. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.03.010 · Cited by 121 · see citing works
Primavesi, F., Maglione, M., Cipriani, F., Denecke, T., Oberkofler, C. E., Starlinger, P., Dasari, B. V. M., Heil, J., Sgarbura, O., Søreide, K., et al. (2023) · British Journal of Surgery · doi:10.1093/bjs/znad233 · Cited by 97 · see citing works
Self-citationThe impact of post-hepatectomy liver failure on mortality: a population-based study
Gilg, S., Sandström, P., Rizell, M., Lindell, G., Ardnor, B., Strömberg, C., & Isaksson, B. (2018) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2018.1501604 · Cited by 95 · see citing works
Current evidence on posthepatectomy liver failure: Comprehensive review
Sparrelid, E., Olthof, P. B., Dasari, B. V. M., Erdmann, J. I., Santol, J., Starlinger, P., & Gilg, S. (2022) · BJS Open · doi:10.1093/bjsopen/zrac142 · Cited by 88 · see citing works
Liu, H., Huang, Y., Cheng, S., Huang, Y.-T., & Lin, P. (2015) · Nutrition Journal · doi:10.1186/s12937-016-0205-6 · Cited by 87 · see citing works
Jara, M., Reese, T., Malinowski, M. B., Valle, E., Seehofer, D., Puhl, G., Neuhaus, P., Pratschke, J., & Stockmann, M. (2015) · HPB · doi:10.1111/hpb.12424 · Cited by 81 · see citing works
Senoner, T., Schindler, S., Stättner, S., Öfner, D., Troppmair, J., & Primavesi, F. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/3950818 · Cited by 77 · see citing works
Self-citationOpen Abdominal Surgery Increases Intraoperative Oxidative Stress: Can It Be Prevented?
Tsuchiya, M., Sato, E. F., Inoue, M., & Asada, A. (2008) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e318187c96b · Cited by 72 · see citing works
The antioxidant effect of green tea catechin ameliorates experimental liver injury
Kobayashi, H., Tanaka, Y., Asagiri, K., Asakawa, T., Tanikawa, K., Kage, M., & Yagi, M. (2010) · Phytomedicine · doi:10.1016/j.phymed.2009.12.006 · Cited by 56 · see citing works
Starlinger, P. P., Pereyra, D., Haegele, S., Braeuer, P., Oehlberger, L., Primavesi, F., Kohler, A., Offensperger, F., Reiberger, T., Ferlitsch, A., et al. (2017) · Hepatology · doi:10.1002/hep.29651 · Cited by 52 · see citing works
Self-citationLoffredo, L., Ben, M. D., Perri, L., Carnevale, R., Nocella, C., Catasca, E., Baratta, F., Ceci, F., Polimeni, L., Gozzo, P., et al. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13687 · Cited by 48 · see citing works
Inflammatory response and oxidative stress during liver resection
Schwarz, C., Fitschek, F., Bar-Or, D., Klaus, D. A., Tudor, B., Fleischmann, E., Roth, G., Tamandl, D., Wekerle, T., Gnant, M., et al. (2017) · PLOS ONE · doi:10.1371/journal.pone.0185685 · Cited by 47 · see citing works
Senoner, T., Velik‐Salchner, C., Luckner, G., & Tauber, H. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/8782387 · Cited by 43 · see citing works
Self-citationIndications for liver surgery in benign tumours
Fodor, M., Primavesi, F., Braunwarth, E., Cardini, B., Resch, T., Bale, R. J., Putzer, D., Henninger, B., Oberhuber, R., Maglione, M., et al. (2018) · European surgery. Supplement/European surgery · doi:10.1007/s10353-018-0536-y · Cited by 41 · see citing works
Self-citationOxidative stress, isoprostanes and hepatic fibrosis.
Comporti, M., Arezzini, B., Signorini, C., Vecchio, D., & Gardi, C. (2009) · PubMed · doi:10.14670/hh-24.893 · Cited by 41 · see citing works
Niederwieser, T., Braunwarth, E., Dasari, B. V. M., Pufal, K., Szatmary, P., Hackl, H., Haselmann, C., Connolly, C. E., Cardini, B., Öfner, D., et al. (2021) · British Journal of Surgery · doi:10.1093/bjs/znab338 · Cited by 39 · see citing works
Self-citationA prospective analysis of oxidative stress and liver transplantation1
Burke, A., FitzGerald, G. A., & Lucey, M. R. (2002) · Transplantation · doi:10.1097/00007890-200207270-00012 · Cited by 36 · see citing works
Uchida, D., Takaki, A., Ishikawa, H., Tomono, Y., Kato, H., Tsutsumi, K., Tamaki, N., Maruyama, T., Tomofuji, T., Tsuzaki, R., et al. (2016) · Free Radical Research · doi:10.3109/10715762.2016.1172071 · Cited by 30 · see citing works
Post Hepatectomy Liver Failure: Concept of Management
Yadav, K. K., Shrikhande, S. V., & Goel, M. (2014) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-014-9646-3 · Cited by 27 · see citing works
Haga, S., Ozawa, T., Yamada, Y., Morita, N., Nagashima, I., Inoue, H., Inaba, Y., Noda, N., Abe, R., Umezawa, K., et al. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5391 · Cited by 26 · see citing works
Cavalca, V., Tremoli, E., Porro, B., Veglia, F., Myasoedova, V. A., Squellerio, I., Manzone, D., Zanobini, M., Trezzi, M., Minno, M. N. D. D., et al. (2013) · Interactive Cardiovascular and Thoracic Surgery · doi:10.1093/icvts/ivt386 · Cited by 23 · see citing works
Liu, H., Cheng, S., Huang, Y., Huang, Y.-T., & Lin, P. (2017) · Nutrients · doi:10.3390/nu9010029 · Cited by 23 · see citing works
Post-Hepatectomy Liver Failure
Chen, J. W., & Barreto, S. G. (2024) · CRC Press eBooks · doi:10.1201/9781003080060-23 · Cited by 22 · see citing works
Baumgartner, R., Engstrand, J., Rajala, P., Grip, J., Ghorbani, P., Sparrelid, E., & Gilg, S. (2023) · British journal of surgery · doi:10.1093/bjs/znad433 · Cited by 18 · see citing works
Essential updates 2021/2022: Update in surgical strategy for perihilar cholangiocarcinoma
Kawano, F., Yoshioka, R., Ichida, H., Mise, Y., & Saiura, A. (2023) · Annals of Gastroenterological Surgery · doi:10.1002/ags3.12734 · Cited by 17 · see citing works
Ayad, A., Hallawa, A., Peine, A., Martin, L., Fazlic, L. B., Dartmann, G., Marx, G., & Schmeink, A. (2022) · JMIR Medical Informatics · doi:10.2196/37658 · Cited by 14 · see citing works
Kong, E., Yuan, C., Li, Y., Tian, T., He, Y., & Feng, X. (2023) · BioMed Research International · doi:10.1155/2023/2763320 · Cited by 14 · see citing works
Akbulut, S., Üremi̇ş, M. M., Sarıcı, K. B., Üremiş, N., Hargura, A. S., Karakaş, S., Dogan, U. G., Türköz, Y., & Yılmaz, S. (2022) · Transplant Immunology · doi:10.1016/j.trim.2022.101697 · Cited by 10 · see citing works
Evaluation of Oxidative Stress in the Late Postoperative Stage of Liver Transplantation
Augusto, V. S., Rodrigues, A. J., Reis, G. S., Silveira, A. P. C., Silva, O. D. C. E., Mente, Ê. D., Jordão, A. A., & Évora, P. R. B. (2014) · Transplantation Proceedings · doi:10.1016/j.transproceed.2013.12.058 · Cited by 10 · see citing works
Perioperative redox changes in patients undergoing hepato-pancreatico-biliary cancer surgery
Stevens, J. L., McKenna, H., Filipe, H., Lau, L. C. K., Fernandez, B. O., Murray, A. J., Feelisch, M., & Martín, D. (2023) · Perioperative Medicine · doi:10.1186/s13741-023-00325-z · Cited by 9 · see citing works
Quality assurance in surgery—a moral obligation
Öfner, D. (2024) · European surgery. Supplement/European surgery · doi:10.1007/s10353-023-00825-8 · Cited by 8 · see citing works
Self-citationHou, J., Wang, Y., Wu, J., Ding, G.-S., Wu, Y., Wei, L., Wang, F., & Zhang, Z.-M. (2023) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v15.i9.1995 · Cited by 7 · see citing works
An oxidative stress-related signature for predicting the prognosis of liver cancer
Wang, L., & Liu, X. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2022.975211 · Cited by 4 · see citing works
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“Especially in major hepatectomies, the postoperative liver function mainly determines the overall course and subsequent morbidity [7,13,35].”
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- Authors
- Primavesi, F., Senoner, T., Schindler, S., Nikolajevic, A., Di Fazio, P., Csukovich, G., Eller, S., Neumayer, B., Anliker, M., Braunwarth, E., Oberhuber, R., Resch, T., Maglione, M., Cardini, B., Niederwieser, T., Gasteiger, S., Klieser, E., Tilg, H., Schneeberger, S., Neureiter, D., Öfner, D., Troppmair, J., & Stättner, S.
- Affiliations
- Innsbruck Medical University (AT)
- Department of Visceral, Thoracic and Vascular Surgery, Philipps-Universität Marburg, 35043 Marburg, Germany
- Paracelsus Medical University (AT)
- Salzburger Landeskliniken (AT)
- Corresponding author
- Primavesi, Florian
- ORCID
- Venue
- Antioxidants
- Publisher
- MDPI AG
- Published
- 2024-05-11
- Volume
- 13
- Issue
- 5
- Pages
- 590
- ISSN
- 2076-3921 (ISSN-L)
- PMC
- PMC11118143
- OpenAlex
- W4396904791
- Cited by
- 3
- References
- 49
- Citations by year
- 2026: 2 · 2025: 1
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Antioxidants (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Universität Innsbruck
- Topics
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- post-hepatectomy liver failure, oxidative stress, hepatectomy, 8-isoprostane, 4-hydroxynonenal, vitamin E, vitamin A, UCP2, cholangiocarcinoma, postoperative mortality, predictive biomarkers, liver function, tumor stage
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