Dalila Costa1, Benedikt Simbrunner2, Mathias Jachs3, Lukas Hartl3, David Bauer2, Rafael Paternostro4, Philipp Schwabl3, Bernhard Scheiner4, Albert Friedrich Stättermayer5, Matthias Pinter5, Michael Trauner5, Mattias Mandorfer3, Thomas Reiberger6. 1. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; Gastroenterology Department, Braga Hospital, Braga, Portugal; Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria. 2. Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. 3. Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria. 4. Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria. 5. Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. 6. Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. Electronic address: thomas.reiberger@meduniwien.ac.at.
Abstract
BACKGROUND & AIMS: Distinct prognostic stages of advanced chronic liver disease (ACLD) are defined by severity of portal hypertension (PH) and the presence/absence of clinical complications. We characterised the degree of liver dysfunction, PH, and systemic inflammation across the distinct prognostic stages and assessed their relative impact on decompensation and mortality. METHODS: A single-centre, prospective cohort of ACLD patients undergoing hepatic venous pressure gradient (HVPG) measurement between 01/2017 and 08/2019 were classified into 6 prognostic stages: mild PH (HVPG 6-9 mmHg, S0), clinically significant PH (HVPG ≥10 mmHg without varices, S1), presence of varices (S2), history of variceal bleeding (S3), first non-bleeding decompensation (S4), and further decompensation (S5). The model for end-stage liver disease (MELD), C-reactive protein (CRP), and IL-6 levels were assessed in relation to their predictive value for decompensation and death. RESULTS: Among 168 ACLD patients 78 had compensated (cACLD, S0 = 13; S1 = 21; S2 = 44) and 90 had decompensated (dACLD, S3 = 10; S4 = 58; S5 = 22) disease. MELD increased across all stages (p <0.001), whereas HVPG mostly increased within cACLD substages. Significant increases in CRP and IL-6 levels were only noted across dACLD substages. IL-6 was an independent predictor of decompensation at 1-year follow-up in cACLD (hazard ratio [HR] 1.06, 95% CI 1.01-1.10; p = 0.013). In dACLD patients, IL-6 levels predicted death/transplantation after 1-year of follow-up (HR 1.02, 95% CI 1.01-1.03; p = 0.004). CONCLUSION: HVPG progression occurs mostly in cACLD patients, whereas systemic inflammation, as reflected by IL-6 levels, only increases substantially across dACLD stages. IL-6 levels correlate with the risk of first decompensation in cACLD and of death/transplantation in dACLD patients. LAY SUMMARY: Patients with advanced chronic liver disease (ACLD; i.e. liver cirrhosis) have a certain risk of mortality according to their stage of disease. Progression of disease is greatly influenced by increased pressure in the portal venous system (i.e. portal hypertension) and occurrence of clinical complications (i.e. decompensation). Our study demonstrates that systemic inflammation markedly increases across highest disease stages, and the inflammation biomarker IL-6 in blood may specifically indicate risk of disease progression in patients with ACLD. CLINICAL TRIALS REGISTRATION: The study is registered at ClinicalTrials.gov (NCT03267615).
BACKGROUND & AIMS: Distinct prognostic stages of advanced chronic liver disease (ACLD) are defined by severity of portal hypertension (PH) and the presence/absence of clinical complications. We characterised the degree of liver dysfunction, PH, and systemic inflammation across the distinct prognostic stages and assessed their relative impact on decompensation and mortality. METHODS: A single-centre, prospective cohort of ACLD patients undergoing hepatic venous pressure gradient (HVPG) measurement between 01/2017 and 08/2019 were classified into 6 prognostic stages: mild PH (HVPG 6-9 mmHg, S0), clinically significant PH (HVPG ≥10 mmHg without varices, S1), presence of varices (S2), history of variceal bleeding (S3), first non-bleeding decompensation (S4), and further decompensation (S5). The model for end-stage liver disease (MELD), C-reactive protein (CRP), and IL-6 levels were assessed in relation to their predictive value for decompensation and death. RESULTS: Among 168 ACLD patients 78 had compensated (cACLD, S0 = 13; S1 = 21; S2 = 44) and 90 had decompensated (dACLD, S3 = 10; S4 = 58; S5 = 22) disease. MELD increased across all stages (p <0.001), whereas HVPG mostly increased within cACLD substages. Significant increases in CRP and IL-6 levels were only noted across dACLD substages. IL-6 was an independent predictor of decompensation at 1-year follow-up in cACLD (hazard ratio [HR] 1.06, 95% CI 1.01-1.10; p = 0.013). In dACLD patients, IL-6 levels predicted death/transplantation after 1-year of follow-up (HR 1.02, 95% CI 1.01-1.03; p = 0.004). CONCLUSION: HVPG progression occurs mostly in cACLD patients, whereas systemic inflammation, as reflected by IL-6 levels, only increases substantially across dACLD stages. IL-6 levels correlate with the risk of first decompensation in cACLD and of death/transplantation in dACLD patients. LAY SUMMARY: Patients with advanced chronic liver disease (ACLD; i.e. liver cirrhosis) have a certain risk of mortality according to their stage of disease. Progression of disease is greatly influenced by increased pressure in the portal venous system (i.e. portal hypertension) and occurrence of clinical complications (i.e. decompensation). Our study demonstrates that systemic inflammation markedly increases across highest disease stages, and the inflammation biomarker IL-6 in blood may specifically indicate risk of disease progression in patients with ACLD. CLINICAL TRIALS REGISTRATION: The study is registered at ClinicalTrials.gov (NCT03267615).
Authors: Theresa Bucsics; Katharina Lampichler; Constantin Vierziger; Maria Schoder; Florian Wolf; David Bauer; Benedikt Simbrunner; Lukas Hartl; Mathias Jachs; Bernhard Scheiner; Michael Trauner; Thomas Gruenberger; Franz Karnel; Mattias Mandorfer; Thomas Reiberger Journal: Dig Dis Sci Date: 2022-03-17 Impact factor: 3.199
Authors: Osman Öcal; Juozas Kupčinskas; Egidijus Morkunas; Holger Amthauer; Kerstin Schütte; Peter Malfertheiner; Heinz Josef Klümpen; Christian Sengel; Julia Benckert; Ricarda Seidensticker; Bruno Sangro; Moritz Wildgruber; Maciej Pech; Peter Bartenstein; Jens Ricke; Max Seidensticker Journal: EJNMMI Res Date: 2021-06-02 Impact factor: 3.138
Authors: Philipp Königshofer; Benedikt Silvester Hofer; Ksenia Brusilovskaya; Benedikt Simbrunner; Oleksandr Petrenko; Katharina Wöran; Merima Herac; Judith Stift; Katharina Lampichler; Gerald Timelthaler; David Bauer; Lukas Hartl; Bernhard Robl; Maria Sibila; Bruno K Podesser; Georg Oberhuber; Philipp Schwabl; Mattias Mandorfer; Michael Trauner; Thomas Reiberger Journal: Hepatology Date: 2021-12-20 Impact factor: 17.298
Authors: Lorenz Balcar; Georg Semmler; Katharina Pomej; Benedikt Simbrunner; David Bauer; Lukas Hartl; Mathias Jachs; Rafael Paternostro; Theresa Bucsics; Matthias Pinter; Michael Trauner; Mattias Mandorfer; Thomas Reiberger; Bernhard Scheiner Journal: United European Gastroenterol J Date: 2021-05 Impact factor: 4.623