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Decreasing systemic inflammation after TIPS: Still hope for the liver: Reply to correspondence on “Insertion of a transjugular intrahepatic portosystemic shunt leads to sustained reversal of systemic inflammation in patients with decompensated liver cirrhosis”

Georg Semmler1,2,3,4orcid, Lorenz Balcar1,2orcid, Mattias Mandorfer1,2orcid
Clinical and Molecular Hepatology 2025;31(2):e224-e225.
Published online: February 17, 2025

1Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria

2Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria

3Centre for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark

4Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

Corresponding author : Georg Semmler Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria Tel: +43 1 40400 47440, Fax: +43 1 40400 47350, E-mail: georg.semmler@meduniwien.ac.at

Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea

• Received: February 8, 2025   • Accepted: February 14, 2025

Copyright © 2025 by The Korean Association for the Study of the Liver

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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See the article "TIPS insertion and systemic inflammation: Is it ever too late to lower portal pressure? Correspondence to editorial on “Insertion of a transjugular intrahepatic portosystemic shunt leads to sustained reversal of systemic inflammation in patients with decompensated liver cirrhosis”" on page e176.
  • Keywords: Cirrhosis; TIPS; Transjugular intrahepatic portosystemic shunt
    • Dear Editor,
    We thank Anja Thiede and Benjamin Maasoumy [1] for adding additional important thoughts on the potential effect of transjugular intrahepatic portosystemic shunt (TIPS) on systemic inflammation (SI) [2,3], highlighting the anti-inflammatory potency of TIPS as being likely higher compared to other treatment options such as non-selective beta-blockers [4,5] a cornerstone for the therapy of clinically significant portal hypertension [6,7]. Just yesterday, the final results from the LIVERHOPE study were published, showing no effect of combined simvastatin 20 mg with rifaximin 1,200 mg on the incidence of acute-on-chronic liver failure or death in patients with decompensated cirrhosis (~80% with ChildPugh B, 90% with previous ascites, but only 37% with ascites grade 2 or 3 at study inclusion) [8]. While only data on Creactive protein (CRP) were shown, these indicated no effect on CRP over the study period or between the simvastatin/rifaximin or placebo groups, which is likely related to a less advanced patient population at study inclusion, as outlined above. Also, median CRP levels were within the normal range at baseline, making any anti-inflammatory effect of such a treatment less likely (compare regression to the mean), acknowledging all limitations of CRP as reflecting the full anti-inflammatory properties of simvastatin/rifaximin. Here, the promising data after TIPS showing a reduction in SI that indeed translated into an improved outcome [9] still give “hope” for a disease-modifying treatment in patients with (refractory) ascites that otherwise suffer from high mortality [10,11], and confirmatory data from randomized controlled trials are eagerly awaited.

    Authors’ contribution

    Drafting of the manuscript (G.S., L.B., M.M.), critical revision of the manuscript for important intellectual content (G.S., L.B., M.M.).

    Conflicts of Interest

    G.S. received travel support from Amgen. L.B. has nothing to disclose. M.M. received grant support from Echosens, served as a consultant and/or advisory board member and/or speaker for AbbVie, Collective Acumen, Echosens, Gilead, Ipsen, Takeda, and W. L. Gore & Associates and received travel support from AbbVie and Gilead.

    CRP

    C-reactive protein

    SI

    systemic inflammation

    TIPS

    transjugular intrahepatic portosystemic shunt
    • 1. Tiede A, Maasoumy B. TIPS insertion and systemic inflammation: Is it ever too late to lower portal pressure: Correspondence to editorial on “Insertion of a transjugular intrahepatic portosystemic shunt leads to sustained reversal of systemic inflammation in patients with decompensated liver cirrhosis”. Clin Mol Hepatol 2025;31:e176-e179.
    • 2. Tiede A, Stockhoff L, Liu Z, Rieland H, Mauz JB, Ohlendorf V, et al. Insertion of a transjugular intrahepatic portosystemic shunt leads to sustained reversal of systemic inflammation in patients with decompensated liver cirrhosis. Clin Mol Hepatol 2025;31:240-255.
    • 3. Semmler G, Balcar L, Mandorfer M. Treating systemic inflammation by transjugular intrahepatic portosystemic shunt: Editorial on “Insertion of a transjugular intrahepatic portosystemic shunt leads to sustained reversal of systemic inflammation in patients with decompensated liver cirrhosis”. Clin Mol Hepatol 2025;31:615-619.
    • 4. Jachs M, Hartl L, Schaufler D, Desbalmes C, Simbrunner B, Eigenbauer E, et al. Amelioration of systemic inflammation in advanced chronic liver disease upon beta-blocker therapy translates into improved clinical outcomes. Gut 2021;70:1758-1767.
    • 5. Reiberger T, Mandorfer M. Beta adrenergic blockade and decompensated cirrhosis. J Hepatol 2017;66:849-859.
    • 6. Liu C, You H, Zeng QL, Wong YJ, Wang B, Grgurevic I, et al. Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306). Clin Mol Hepatol 2025;31:105-118.
    • 7. Brujats A, Villanueva C. Examining the therapeutic landscape of beta-blockers in portal hypertension. Clin Mol Hepatol 2024;30:1055-1059.
    • 8. Pose E, Jiménez C, Zaccherini G, Campion D, Piano S, Uschner FE, et al. Simvastatin and rifaximin in decompensated cirrhosis: A randomized clinical trial. JAMA 2025;333:864-874.
    • 9. Kornfehl A, Tiede A, Hemetsberger P, Kappel J, Müllner-Bucsics T, Stockhoff L, et al. Decreasing interleukin-6 levels after TIPS predict outcomes in decompensated cirrhosis. JHEP Reports 2024;7:101308.
    • 10. Balcar L, Tonon M, Semmler G, Calvino V, Hartl L, Incicco S, et al. Risk of further decompensation/mortality in patients with cirrhosis and ascites as the first single decompensation event. JHEP Rep 2022;4:100513.
    • 11. Tonon M, Balcar L, Semmler G, Calvino V, Scheiner B, Incicco S, et al. Etiological cure prevents further decompensation and mortality in patients with cirrhosis with ascites as the single first decompensating event. Hepatology 2023;78:1149-1158.

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    Decreasing systemic inflammation after TIPS: Still hope for the liver: Reply to correspondence on “Insertion of a transjugular intrahepatic portosystemic shunt leads to sustained reversal of systemic inflammation in patients with decompensated liver cirrhosis”
    Clin Mol Hepatol. 2025;31(2):e224-e225.   Published online February 17, 2025
    DOI: https://doi.org/10.3350/cmh.2025.0149
    Download Citation

    Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.
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    Include:
    Decreasing systemic inflammation after TIPS: Still hope for the liver: Reply to correspondence on “Insertion of a transjugular intrahepatic portosystemic shunt leads to sustained reversal of systemic inflammation in patients with decompensated liver cirrhosis”
    Clin Mol Hepatol. 2025;31(2):e224-e225.   Published online February 17, 2025
    DOI: https://doi.org/10.3350/cmh.2025.0149
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