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”

Article information

Clin Mol Hepatol. 2025;31(2):e224-e225

Publication date (electronic) : 2025 February 17

doi : https://doi.org/10.3350/cmh.2025.0149

Georg Semmler^,¹^,²^,³^,⁴

, Lorenz Balcar ¹^,²

, Mattias Mandorfer ¹^,²

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 2025 February 8; Accepted 2025 February 14.

See the Original "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.

Notes

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.

Abbreviations

CRP

C-reactive protein

systemic inflammation

TIPS

transjugular intrahepatic portosystemic shunt

References

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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