Insertion of a transjugular intrahepatic portosystemic shunt leads to sustained reversal of systemic inflammation in patients with decompensated liver cirrhosis

Tiede, Anja; Stockhoff, Lena; Liu, Zhaoli; Rieland, Hannah; Mauz, Jim B.; Ohlendorf, Valerie; Bremer, Birgit; Witt, Jennifer; Kraft, Anke; Cornberg, Markus; Hinrichs, Jan B.; Meyer, Bernhard C.; Wedemeyer, Heiner; Xu, Cheng-Jian; Falk, Christine S.; Maasoumy, Benjamin

doi:2025.31.1.240

Clin Mol Hepatol > Volume 31(1); 2025 > Article

Original Article

Clinical and Molecular Hepatology 2025;31(1): 240-255.
doi: https://doi.org/10.3350/cmh.2024.0587

Insertion of a transjugular intrahepatic portosystemic shunt leads to sustained reversal of systemic inflammation in patients with decompensated liver cirrhosis

Anja Tiede^1,2, Lena Stockhoff^1,3, Zhaoli Liu^4,5, Hannah Rieland¹, Jim B. Mauz¹, Valerie Ohlendorf¹, Birgit Bremer¹, Jennifer Witt¹, Anke Kraft^1,2,4,5, Markus Cornberg^1,2,4,5,6, Jan B. Hinrichs^7,8, Bernhard C. Meyer⁸, Heiner Wedemeyer^1,2,6, Cheng-Jian Xu^4,5, Christine S. Falk^6,9, Benjamin Maasoumy^1,2,6

¹Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
²German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
³Niels-Stensen-Kliniken Marienhospital, Osnabrück, Germany
⁴Center for Individualized Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
⁵TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
⁶Cluster of Excellence RESIST (EXC2155), Hannover Medical School, Hannover, Germany
⁷St. Bernward Hospital, Radiology, Hildesheim, Germany
⁸Hannover Medical School, Department of Diagnostic and Interventional Radiology, Hannover, Germany
⁹Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany

Correspondence :

Benjamin Maasoumy ,
Tel: +49 511 532-6529, Fax: +49-511 532-4896, Email: Maasoumy.benjamin@mh-hannover.de

Received: July 22, 2024 Revised: November 4, 2024 Accepted: November 18, 2024
*Anja Tiede and Lena Stockhoff contributed equally to this work.

ABSTRACT

Background/Aims
Systemic Inflammation (SI) is considered a key mechanism in disease progression and development of complications in decompensated liver cirrhosis. SI is mainly driven by portal hypertension and bacterial translocation. Transjugular intrahepatic portosystemic shunt (TIPS) insertion represents an effective treatment for portal hypertension. This study aims to investigate the impact of TIPS insertion on SI and bacterial translocation.
Methods
We prospectively included 59 cirrhotic patients undergoing TIPS insertion. Blood samples were collected at TIPS insertion and follow-up (FU) 1, 3, 6, and 12 months thereafter. At all time points, we performed a comprehensive analysis of SI including 43 soluble inflammatory markers (SIMs), and surrogates of bacterial translocation (sCD14, sCD163). To investigate long-term kinetics of SI, C-reactive protein (CRP) and white blood cells (WBC) were retrospectively analyzed in a cohort of 177 patients up to 3 years after TIPS insertion.
Results
At TIPS insertion, 30/43 SIMs, sCD14, and sCD163 measured significantly higher in cirrhotic patients compared to healthy controls. By FU6 25 SIMs and sCD14 measured at significantly lower levels compared to baseline. Interestingly, in patients with TIPS indication of refractory ascites, IL-6 decreased to levels documented in earlier stages of cirrhosis. In long-term follow-up, CRP levels significantly decreased after TIPS insertion, which translated into lower mortality in Cox regression analysis (HR 0.968, p=0.042). Notably, patients with residual ascites post-TIPS showed significantly higher CRP and IL-6 levels across all follow-ups compared to patients with resolved ascites.
Conclusions
Decreasing portal hypertension via TIPS insertion leads to a significant attenuation of SI and bacterial translocation over time.

KeyWords: Transjugular intrahepatic portosystemic shunt insertion; Systemic inflammation; Liver cirrhosis; Portal hypertension; Bacterial translocation