Henning Grønbæk1, Sidsel Rødgaard-Hansen2, Niels Kristian Aagaard3, Vicente Arroyo4, Søren K Moestrup5, Elisabet Garcia4, Elsa Solà6, Marco Domenicali7, Salvatore Piano8, Hendrik Vilstrup3, Holger Jon Møller2. 1. Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: Henngroe@rm.dk. 2. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. 4. The EASL-CLIF Consortium, Barcelona, Spain. 5. Department of Biomedicine, Aarhus University, Aarhus & Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. 6. Liver Unit, Hospital Clinic de Barcelona, Unviersity of Barcelona, IDIBAPS, CIBEReHD, Barcelona, Spain. 7. Department of Medical and Surgical Sciences, University of Bologna, Italy. 8. Unit of Hepatic Emergencies and Liver Transplantation, Department of Medicine-DIMED, University of Padova, Padova, Italy.
Abstract
BACKGROUND & AIMS: Activation of liver macrophages plays a key role in liver and systemic inflammation and may be involved in development and prognosis of acute-on-chronic liver failure (ACLF). We therefore measured the circulating macrophage activation markers soluble sCD163 and mannose receptor (sMR) and related them to the short-(1-3 months) and long-term (6 months) mortality in the cirrhosis patients of the CANONIC study. METHODS: Eighty-six cirrhosis patients had no ascites and no ACLF, 580 had ascites but no ACLF; 100, 66, and 19 had ACLF-grade-I (ACLF-I), ACLF-II, and ACLF-III, respectively. The patients' clinical course was registered and their MELD, CLIF-C Acute Decompensation (AD), and CLIF-C ACLF-scores computed at inclusion. RESULTS: We found a stepwise increase (p<0.001) in median sCD163 (5.68 (IQR: 3.86-9.60); 8.26 (5.02-12.34); 9.50 (5.37-17.91); 15.68 (10.12-19.42); 20.18 (15.26-32.20) mg/L) and sMR (0.60 (0.40-0.84); 0.81 (0.57-1.12); 0.81 (0.61-1.26); 1.17 (0.89-1.62); 1.41 (1.14-1.79)mg/L) with increasing grades of ACLF. Both sCD163 and sMR were independently associated with short and long-term mortality and showed equal or higher predictive accuracy than MELD, CLIF-C ACLF and CLIF-C AD scores. Addition of the macrophage markers to the clinical scores improved the prognostic efficacy: In ACLF patients sCD163 improved prediction of short-term mortality (C-index: 0.74 (0.67-0.80)) and in patients without ACLF sMR improved prediction of long-term mortality (C-index: 0.80 (0.76-0.85)). CONCLUSIONS: The severity related increase in sCD163 and sMR and close association with mortality suggest a primary importance of inflammatory activation of liver macrophages in the emergence and course of ACLF. Accordingly, supplementation of the macrophage biomarkers to the platform of the clinical scores improved the prognostic performance beyond that of the original scores.
BACKGROUND & AIMS: Activation of liver macrophages plays a key role in liver and systemic inflammation and may be involved in development and prognosis of acute-on-chronic liver failure (ACLF). We therefore measured the circulating macrophage activation markers soluble sCD163 and mannose receptor (sMR) and related them to the short-(1-3 months) and long-term (6 months) mortality in the cirrhosispatients of the CANONIC study. METHODS: Eighty-six cirrhosispatients had no ascites and no ACLF, 580 had ascites but no ACLF; 100, 66, and 19 had ACLF-grade-I (ACLF-I), ACLF-II, and ACLF-III, respectively. The patients' clinical course was registered and their MELD, CLIF-C Acute Decompensation (AD), and CLIF-C ACLF-scores computed at inclusion. RESULTS: We found a stepwise increase (p<0.001) in median sCD163 (5.68 (IQR: 3.86-9.60); 8.26 (5.02-12.34); 9.50 (5.37-17.91); 15.68 (10.12-19.42); 20.18 (15.26-32.20) mg/L) and sMR (0.60 (0.40-0.84); 0.81 (0.57-1.12); 0.81 (0.61-1.26); 1.17 (0.89-1.62); 1.41 (1.14-1.79)mg/L) with increasing grades of ACLF. Both sCD163 and sMR were independently associated with short and long-term mortality and showed equal or higher predictive accuracy than MELD, CLIF-C ACLF and CLIF-C AD scores. Addition of the macrophage markers to the clinical scores improved the prognostic efficacy: In ACLF patients sCD163 improved prediction of short-term mortality (C-index: 0.74 (0.67-0.80)) and in patients without ACLF sMR improved prediction of long-term mortality (C-index: 0.80 (0.76-0.85)). CONCLUSIONS: The severity related increase in sCD163 and sMR and close association with mortality suggest a primary importance of inflammatory activation of liver macrophages in the emergence and course of ACLF. Accordingly, supplementation of the macrophage biomarkers to the platform of the clinical scores improved the prognostic performance beyond that of the original scores.
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: Detlef Schuppan; Henning Grønbæk; Konstantin Kazankov; Simon Mark Dahl Jørgensen; Karen Louise Thomsen; Holger Jon Møller; Hendrik Vilstrup; Jacob George Journal: Nat Rev Gastroenterol Hepatol Date: 2019-03 Impact factor: 46.802
Authors: F Rainer; A Horvath; T D Sandahl; B Leber; B Schmerboeck; A Blesl; A Groselj-Strele; R E Stauber; P Fickert; P Stiegler; H J Møller; H Grønbaek; V Stadlbauer Journal: Aliment Pharmacol Ther Date: 2017-12-21 Impact factor: 8.171
Authors: Nikolaj Worm Ørntoft; Michel Blé; Anna Baiges; Jose Ferrusquia; Virginia Hernández-Gea; Fanny Turon; Marta Magaz; Søren Møller; Holger Jon Møller; Juan Carlos Garcia-Pagan; Henning Gronbaek Journal: Front Physiol Date: 2021-06-11 Impact factor: 4.566