BACKGROUND & AIMS: CXCR% ligands play an important role in hepatic injury, inflammation and fibrosis. While CXCL9 and CXCL11 are associated with survival in patients receiving transjugular intrahepatic portosystemic shunt (TIPS), the role of CXCL10 in severe portal hypertension remains unknown. METHODS: A total of 89 cirrhotic patients were analysed. CXCL10 protein levels were measured in portal and hepatic blood at TIPS insertion and 2 weeks later in 24 patients. CXCL10 and IL8 levels were assessed in portal, hepatic, cubital vein and right atrium blood in a further 25 patients at TIPS insertion. Furthermore, real-time PCR determined hepatic CXCL10-mRNA in 40 cirrhotic patients. RESULTS: Hepatic CXCL10 showed no association with decompensation. By contrast, circulating CXCL10-levels were higher in portal than in hepatic vein blood, suggesting an extrahepatic source of CXCL10 in cirrhosis. However, CXCL10 protein in blood samples from portal, hepatic, cubital veins and right atrium correlated excellently with each other and with IL-8 levels. Higher CXCL10 circulating levels were associated with presence of ascites and higher Child scores. Higher CXCL10 circulating protein levels were associated with acute decompensation, acute-on-chronic liver failure (ACLF) and independently with mortality. Moreover, a decrease in CXCL10 protein levels after TIPS insertion was associated with better survival in each cohort and analysed together. DISCUSSION: Circulating CXCL10 possibly reflects systemic inflammation and it is correlated with acute decompensation, ACLF and complications in patients with severe portal hypertension receiving TIPS. CXCL10 predicts survival in these patients and a decrease in CXCL10 after TIPS may be considered a good prognostic factor.
BACKGROUND & AIMS: CXCR% ligands play an important role in hepatic injury, inflammation and fibrosis. While CXCL9 and CXCL11 are associated with survival in patients receiving transjugular intrahepatic portosystemic shunt (TIPS), the role of CXCL10 in severe portal hypertension remains unknown. METHODS: A total of 89 cirrhotic patients were analysed. CXCL10 protein levels were measured in portal and hepatic blood at TIPS insertion and 2 weeks later in 24 patients. CXCL10 and IL8 levels were assessed in portal, hepatic, cubital vein and right atrium blood in a further 25 patients at TIPS insertion. Furthermore, real-time PCR determined hepatic CXCL10-mRNA in 40 cirrhotic patients. RESULTS: Hepatic CXCL10 showed no association with decompensation. By contrast, circulating CXCL10-levels were higher in portal than in hepatic vein blood, suggesting an extrahepatic source of CXCL10 in cirrhosis. However, CXCL10 protein in blood samples from portal, hepatic, cubital veins and right atrium correlated excellently with each other and with IL-8 levels. Higher CXCL10 circulating levels were associated with presence of ascites and higher Child scores. Higher CXCL10 circulating protein levels were associated with acute decompensation, acute-on-chronic liver failure (ACLF) and independently with mortality. Moreover, a decrease in CXCL10 protein levels after TIPS insertion was associated with better survival in each cohort and analysed together. DISCUSSION: Circulating CXCL10 possibly reflects systemic inflammation and it is correlated with acute decompensation, ACLF and complications in patients with severe portal hypertension receiving TIPS. CXCL10 predicts survival in these patients and a decrease in CXCL10 after TIPS may be considered a good prognostic factor.
Authors: Delia Blaya; Elisa Pose; Mar Coll; Juan José Lozano; Isabel Graupera; Robert Schierwagen; Christian Jansen; Pedro Castro; Sara Fernandez; Julia Sidorova; Mariuca Vasa-Nicotera; Elsa Solà; Joan Caballería; Jonel Trebicka; Pere Ginès; Pau Sancho-Bru Journal: JHEP Rep Date: 2021-01-19
Authors: Jonel Trebicka; Alex Amoros; Carla Pitarch; Esther Titos; José Alcaraz-Quiles; Robert Schierwagen; Carmen Deulofeu; Javier Fernandez-Gomez; Salvatore Piano; Paolo Caraceni; Karl Oettl; Elsa Sola; Wim Laleman; Jane McNaughtan; Rajeshwar P Mookerjee; Minneke J Coenraad; Tania Welzel; Christian Steib; Rita Garcia; Thierry Gustot; Miguel A Rodriguez Gandia; Rafael Bañares; Agustin Albillos; Stefan Zeuzem; Victor Vargas; Faouzi Saliba; Frederic Nevens; Carlo Alessandria; Andrea de Gottardi; Heinz Zoller; Pere Ginès; Tilman Sauerbruch; Alexander Gerbes; Rudolf E Stauber; Mauro Bernardi; Paolo Angeli; Marco Pavesi; Richard Moreau; Joan Clària; Rajiv Jalan; Vicente Arroyo Journal: Front Immunol Date: 2019-03-19 Impact factor: 7.561
Authors: Jennifer Lehmann; Michael Praktiknjo; Mette Juul Nielsen; Robert Schierwagen; Carsten Meyer; Daniel Thomas; Francesco Violi; Christian P Strassburg; Flemming Bendtsen; Søren Møller; Aleksander Krag; Morten Asser Karsdal; Diana Julie Leeming; Jonel Trebicka Journal: Liver Int Date: 2019-03-07 Impact factor: 5.828
Authors: Robert Schierwagen; Frank E Uschner; Cristina Ortiz; Sandra Torres; Max J Brol; Olaf Tyc; Wenyi Gu; Christian Grimm; Stefan Zeuzem; Andreas Plamper; Philipp Pfeifer; Sebastian Zimmer; Christoph Welsch; Liliana Schaefer; Karl P Rheinwalt; Joan Clària; Vicente Arroyo; Jonel Trebicka; Sabine Klein Journal: Front Immunol Date: 2020-07-07 Impact factor: 7.561