Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2017 Oct 18;12(10):e0185685.
doi: 10.1371/journal.pone.0185685. eCollection 2017.

Inflammatory response and oxidative stress during liver resection

Christoph Schwarz  1   2 , Fabian Fitschek  1 , David Bar-Or  3   4   5   6 , Daniel A Klaus  7 , Bianca Tudor  7 , Edith Fleischmann  7 , Georg Roth  7 , Dietmar Tamandl  8 , Thomas Wekerle  2 , Michael Gnant  1 , Martin Bodingbauer  1 , Klaus Kaczirek  1
Affiliations
Observational Study

Inflammatory response and oxidative stress during liver resection

Christoph Schwarz et al. PLoS One. .

Abstract

Background: Postoperative complications are still a major concern after liver resection (LR). Systemic inflammation and deregulated reactive oxygen species during major abdominal surgery may impair outcome after hepatectomy.

Methods: Patients undergoing LR were included in this study (n = 40). Oxidative stress (OS) was measured peri- and post-operatively as static oxidation-reduction potential markers (sORP) and antioxidant capacity ORP (cORP) by using the RedoxSYS Diagnostic system. Furthermore, Th1- and Th2-specific cytokines were assessed.

Results: Whereas there was no significant change in systemic sORP during LR and in the early postoperative course, there was a substantial decrease of cORP immediately post-surgery, and on postoperative days 1 and 3 (p<0.001). OS response was tightly regulated, as there was a significant correlation between sORP and cORP (p<0.0001; R2:0.457). An increase of OS (sORP) after LR of more than 3 mV was predictive for severe postoperative complications (53.8% vs. 12.5; p = 0.017). There was a significantly higher IL-2 (p = 0.006) and IL-5 (p = 0.001) increase during hepatectomy in patients who developed a severe morbidity.

Conclusion: Antioxidant capacity remained stable during LR but dropped during the post-surgical period, suggesting a consumption of antioxidants to maintain OS within healthy range. Severe postoperative complications were associated with a pronounced inflammatory response during surgery.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: DBO is a co- inventor of the RedoxSys system technology and holds multiple patents on the ORP galvanostatic instrument (RedoxSys) and ORP strips (all assigned to AYTU) including: US 8,317,997; US 8,329,012; US 8,641,888; US 9,372,167; US 9,034,159; US 9,528,959; US 9,410,913; Australia 2012223511; Canada 2,817,163; China 201280004390.9; China 201380026221.X; Japan 5834319; Japan 5985739. Furthermore, he owns options in the company. All other authors have no conflict of interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Oxidative stress (OS) during liver resection.
(A) OS measured as static oxidative reduction potential (sORP) remains relatively stable during and after liver resection. (B) However, capacity oxidative reduction potential (cORP) significantly decreases after surgery and on postoperative day 1 and 3 (p<0.001). (C, D) Both, OS and capacity in the in- and outflow of the liver (portal vein, hepatic vein) remained virtually unchanged before and after liver resection, respectively. (E) OS is tightly regulated, as there was a significant correlation between sORP and cORP measured systemically (p<0.0001; R2: 0.458). Data are expressed as means with standard error of the mean (SEM) and comparison was performed by using a paired t-test (A, B) or an unpaired t-test (C, D). Correlation was calculated by using the Pearson-test (D). n.s. non significant, *** p<0.001, **** p<0.0001.
Fig 2
Fig 2. Change in OS is associated with severe post-operative complication.
(A) Mean sORP increase during LR was higher in patients who developed a severe post-operative complication compared to patients with no/minor post-operative complication (0.6 (3.6) mV vs. 7.4 (8.1) mV; p = 0.386). (B) Measuring the increase of OS after LR revealed a significantly increased response in patients with severe morbidity compared to patients without (-5.3 (3.3) mV vs. 10.5 (7.3) mV; p = 0.028). Data are expressed as means with standard error of the mean (SEM) and comparison was performed by using an unpaired t-test.* p<0.05.
Fig 3
Fig 3. Cytokines during liver resection.
Classical Th1 (A, B) and TH2 cytokines (C, D) were measured perioperatively. Even though there was a trend towards higher values of IL-2 (A), INF-y (B), IL-4 (C), IL-5 (D) and GM-CSF (F) perioperatively, the observed differences did not reach statistical significance. (E) Patients with severe post-operative complication had significantly higher levels of IL-6, measured POD3 (24.6 (3.1) pg/ml vs. (53.7 (13.8) pg/ml; p = 0.004). Data are expressed as means with standard error of the mean (SEM) and comparison was performed by using an unpaired t-test.** p <0.01.
Fig 4
Fig 4. Inflammatory response during and after liver resection.
(A) Mean interleukin-2 (IL-2) increase during surgery was more pronounced in patients, who developed severe postoperative complication (-5.1 (2.2) pg/ml vs. 9.8 (6.1) pg/ml; p = 0.006). (B) Similar to that, there was a trend towards an increased interferon-gamma (INF-y) response (p = 0.085). (C, D) Whereas there was only a trend towards a higher IL-4 increase during liver resection, an higher interleukin-5 (IL-5) increase during hepatectomy was predictive for severe postoperative complication (-2 (0.7) pg/ml vs. 3.2 (1.7) pg/ml; p = 0.001). (E) There was no significant difference regarding perioperative IL-6 increase. (F) Perioperative increase in granulocyte macrophage colony-stimulating factor (GM-CSF) was higher in patients with major complication compared to patients without, however the observed difference did not reach statistical significance. Data are expressed as means with standard error of the mean (SEM) and comparison was performed by using an unpaired t-test.** p<0.01.
See this image and copyright information in PMC

References

    1. Bleriot C, Dupuis T, Jouvion G, Eberl G, Disson O, Lecuit M. Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection. Immunity. 2015;42(1):145–58. doi: 10.1016/j.immuni.2014.12.020 - DOI - PubMed
    1. Gao B, Jeong WI, Tian Z. Liver: An organ with predominant innate immunity. Hepatology. 2008;47(2):729–36. doi: 10.1002/hep.22034 - DOI - PubMed
    1. Xu MJ, Feng D, Wu H, Wang H, Chan Y, Kolls J, et al. Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy: a critical role for IL-6/STAT3. Hepatology. 2015;61(2):692–702. doi: 10.1002/hep.27447 - DOI - PMC - PubMed
    1. Balmer ML, Slack E, de Gottardi A, Lawson MA, Hapfelmeier S, Miele L, et al. The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Science translational medicine. 2014;6(237):237ra66 doi: 10.1126/scitranslmed.3008618 - DOI - PubMed
    1. Clavien PA, Petrowsky H, DeOliveira ML, Graf R. Strategies for safer liver surgery and partial liver transplantation. The New England journal of medicine. 2007;356(15):1545–59. doi: 10.1056/NEJMra065156 - DOI - PubMed

Publication types

LinkOut - more resources