Moana Witte, Carlos Oltmanns, Jan Tauwaldt, Hagen Schmaus, Jasmin Mischke, Gordon Grabert, Mara Bretthauer, Lennart M. Roesner, Thomas Werfel, Katja Deterding, Benjamin Maasoumy, Heiner Wedemeyer, Tim Kacprowski, Anke R.M. Kraft, Markus Cornberg
Clin Mol Hepatol 2025;31(4):1269-1284. Published online June 4, 2025
Background/Aims Hepatitis C virus (HCV) infection remains a global health challenge, leading to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Despite the high efficacy of direct-acting antiviral therapy in achieving sustained virologic response (SVR), concerns persist regarding long-term immune alterations and residual risks, particularly in cirrhotic patients.
Methods This study investigates 75 soluble immune mediator (SIM) profiles in 102 chronic HCV patients, stratified by cirrhosis status, at therapy initiation, end of treatment, and long-term follow-up (median 96 weeks). Findings were compared with 51 matched healthy controls and validated in an independent cohort of 47 cirrhotic patients, 17 of whom developed HCC.
Results We observed significant SIM alterations at baseline, with cirrhotic patients displaying a more profoundly dysregulated inflammatory milieu. Despite an overall decline in inflammatory markers following SVR, persistent alterations were evident, particularly in cirrhotic patients. Notably, those with liver stiffness exceeding 14 kPa exhibited sustained inflammatory dysregulation, correlating with liver elastography values. Key SIM such as interleukin (IL)-6, IL-8, urokinase plasminogen activator, and hepatocellular growth factor remained elevated and were associated with HCC development. Network analysis highlighted their roles in liver fibrosis, regeneration, and carcinogenesis.
Conclusions These findings underscore the importance of early antiviral intervention to prevent cirrhosis-related sequelae. Future studies should explore the mechanistic pathways linking chronic inflammation, fibrosis, and oncogenesis to identify predictive biomarkers and novel therapeutic targets. Addressing persistent immune alterations post-HCV clearance may improve long-term outcomes, particularly in patients with advanced liver disease.
Citations
Citations to this article as recorded by
HBV Dominance Is Associated With a Distinct Inflammatory Milieu in HBV/HCV Coinfection Carlos Oltmanns, Moana Witte, Anika Wranke, Katja Deterding, Heiner Wedemeyer, Christine S. Falk, Anke R. M. Kraft, Steffen B. Wiegand, Markus Cornberg Journal of Viral Hepatitis.2025;[Epub] CrossRef
2,469
View
114
Download
Crossref
Correspondence
Liver fibrosis, cirrhosis, and portal hypertension
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 cirrh Georg Semmler, Lorenz Balcar, Mattias Mandorfer Clinical and Molecular Hepatology.2025; 31(2): e224. CrossRef
Advancing our understanding of recompensated cirrhosis - the new “holy grail” of decompensated cirrhosis Thomas Reiberger, Benjamin Maasoumy Journal of Hepatology.2025; 83(3): 615. CrossRef
TIPS Outcomes in Cirrhosis with Sarcopenia: Overt Hepatic Encephalopathy, Improvement in Sarcopenia and Mortality— Systematic Review and Meta-analysis Maria de Brito Nunes, Maria Gabriela Delgado, Jaume Bosch, Annalisa Berzigotti JHEP Reports.2025; : 101699. CrossRef
Anja Tiede, Lena Stockhoff, Zhaoli Liu, Hannah Rieland, Jim B. Mauz, Valerie Ohlendorf, Birgit Bremer, Jennifer Witt, Anke Kraft, Markus Cornberg, Jan B. Hinrichs, Bernhard C. Meyer, Heiner Wedemeyer, Cheng-Jian Xu, Christine S. Falk, Benjamin Maasoumy
Clin Mol Hepatol 2025;31(1):240-255. Published online November 21, 2024
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.
Citations
Citations to this article as recorded by
Systemic inflammatory indexes as predictors of 18-month mortality among cirrhotic patients receiving transjugular intrahepatic portosystemic shunt Jie Cheng, Xiaobing Wang, Lihua Zhou, Xiaojia Chen, Nuer Tang, Feng Zhou, Feng Ding, Yuan Yang, Jun Lin, Liping Chen Annals of Medicine.2025;[Epub] CrossRef
Advancing our understanding of recompensated cirrhosis - the new “holy grail” of decompensated cirrhosis Thomas Reiberger, Benjamin Maasoumy Journal of Hepatology.2025; 83(3): 615. CrossRef
Transjugular Intrahepatic Portosystemic Shunt (TIPS) Promotes Wound Healing in Cirrhotic Patients With Post‐Splenectomy Complications Na Han, Xulong Yuan, Zhengcai Liu, Yuanping Xu, Shuqiang Yue, Yongquan Shi, Jun Tie Portal Hypertension & Cirrhosis.2025; 4(3): 189. CrossRef
TIPSEMS‐VB Trial Reappraised: Infection Control, HE Prophylaxis, and Ischemic Hepatitis Considerations Kaiyu Bian, Yujie Zhang, Xiang Ma Liver International.2025;[Epub] CrossRef
Refining Prognosis in Cirrhosis Patients With Ascites: Impact of Acute vs. Non‐Acute Decompensation Lucie Simonis, Lorenz Balcar, Anna Schedlbauer, Marta Tonon, Nikolaj Torp, Valeria Santori, Katharina Stopfer, Jan Embacher, Christian Sebesta, Leonie Hafner, Benedikt Silvester Hofer, Nina Dominik, Georg Kramer, Paul Thöne, Michael Trauner, Aleksander Kr Alimentary Pharmacology & Therapeutics.2025; 62(11-12): 1202. CrossRef
Reply Martin A. Kabelitz, Lisa Sandmann, Benjamin Maasoumy Clinical Gastroenterology and Hepatology.2025;[Epub] CrossRef
Editorial: Redefining Decompensation in Cirrhosis—More Than an Academic Playground? Anja Tiede, Benjamin Maasoumy Alimentary Pharmacology & Therapeutics.2025; 62(11-12): 1230. CrossRef
Editorial: Redefining Decompensation in Cirrhosis—More Than an Academic Playground? Authors' Reply Lucie Simonis, Lorenz Balcar, Georg Kramer, Thomas Reiberger, Georg Semmler Alimentary Pharmacology & Therapeutics.2025; 62(11-12): 1233. CrossRef
Effectiveness of controlled-expansion transjugular intrahepatic portosystemic shunt (CX-TIPS) in an interdisciplinary setting at a large tertiary center Marlene Hintersteininger, Julia Kappel, Theresa Müllner-Buscics, Susanna Riegler, Nina Dominik, Georg Kramer, Christian Sebesta, Paul Thöne, Albert Friedrich Stättermayer, Lukas Reider, Maria Schoder, Catharina Klausenitz, Raoul Varga, Fredrik Waneck, Mic Wiener klinische Wochenschrift.2025;[Epub] CrossRef
Prävention der Dekompensation bei einer fortgeschrittenen Lebererkrankung Marlene Reincke, Lukas Sturm, Robert Thimme, Dominik Bettinger DMW - Deutsche Medizinische Wochenschrift.2025; 150(21): 1267. CrossRef
Treatment response to bulevirtide is linked to amelioration of portal hypertension in patients with chronic hepatitis D☆ Lisa Sandmann, Mathias Jachs, Tammo L. Tergast, Lukas Hartl, Birgit Bremer, Martin A. Kabelitz, Michael Schwarz, Julius F.M. Egge, Lorenz Balcar, Benedikt Silvester Hofer, Christine S. Falk, Albert Friedrich Stättermayer, Markus Cornberg, Michael Trauner, JHEP Reports.2025; : 101643. CrossRef
Neurofilament Light Chains in Serum Predict Post—Transjugular Intrahepatic Portosystemic Shunt Hepatic Encephalopathy Christian Labenz, Eva Maria Schleicher, Myriam Meineck, Martin A. Kabelitz, Alena F. Ehrenbauer, Anja Tiede, Jim B. Mauz, Sven Danneberg, Michael Bernhard Pitton, Falk Steffen, Julia Weinmann‐Menke, Peter Robert Galle, Stefan Bittner, Felix Lüssi, Jens Uw MedComm.2025;[Epub] CrossRef
Decreasing interleukin-6 levels after TIPS predict outcomes in decompensated cirrhosis Andrea Kornfehl, Anja Tiede, Paul Hemetsberger, Julia Kappel, Theresa Müllner-Bucsics, Lena Stockhoff, Hannah Rieland, Lukas Reider, Nina Dominik, Georg Kramer, Michael Trauner, Mattias Mandorfer, Christine Falk, Benjamin Maasoumy, Thomas Reiberger, Lukas JHEP Reports.2024; : 101308. CrossRef
First
Prev
