Lars Bossen1,2,3, Paola Rebora4, Francesca Bernuzzi2, Peter Jepsen1,3,5, Alessio Gerussi2,6, Pietro Andreone7,8, Andrea Galli9, Benedetta Terziroli10, Domenico Alvaro11,12, Giancarlo Labbadia13, Chiara Aloise2, Leonardo Baiocchi14, Edoardo Giannini15, Ludovico Abenavoli16, Pierluigi Toniutto17, Fabio Marra10, Marco Marzioni18, Grazia Niro19, Annarosa Floreani20,21, Holger J Møller22, Maria G Valsecchi4, Marco Carbone2,6, Henning Grønbaek1,3, Pietro Invernizzi2,6. 1. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. 2. Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy. 3. European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Aarhus University Hospital, Aarhus, Denmark. 4. Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milan Bicocca, Milan, Italy. 5. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. 6. European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy. 7. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. 8. European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Policlinico San Orsola - Universitaria di Bologna, Bologna, Italy. 9. Division of Gastroenterology, University of Florence, Florence, Italy. 10. Epatocentro, Lugano, Switzerland. 11. Division of Gastroenterology, University of Rome La Sapienza, Rome, Italy. 12. European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Sapenzia University of Rome, Rome, Italy. 13. Internal Medicine, University of Rome La Sapienza, Rome, Italy. 14. Division of Hepatology, University of Rome Tor Vergata, Rome, Italy. 15. Division of Gastroenterology, University of Genova, Genova, Italy. 16. Division of Gastroenterology, University of Catanzaro, Catanzaro, Italy. 17. Division of Hepatology, University of Udine, Udine, Italy. 18. Division of Gastroenterology, University of Ancona, Ancona, Italy. 19. Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Italy. 20. Division of Gastroenterology, University of Padova, Padova, Italy. 21. European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Azienda Ospedaliera - Universitaria di Padova, Padova, Italy. 22. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Abstract
INTRODUCTION: In primary biliary cholangitis (PBC), macrophages are involved in liver inflammation and fibrosis. The macrophage activation markers, soluble (s)CD163 and mannose receptor (sMR) are associated with liver disease severity and prognosis in other chronic liver diseases. We aimed to investigate sCD163 and sMR in patients with PBC. METHODS: We investigated PBC patients from the Italian PBC Study Group cohort and measured macrophage activation markers in serum at study enrolment. Patients were followed from enrolment until they experienced an event or were censored at their last visit. Events were defined as follows: (a) death from a liver-related cause; or (b) liver transplantation (LT) for PBC. We used Cox regression to investigate the association between sCD163 and sMR and long-term prognosis. RESULTS: In total, 202 PBC patients were included. Median age was 62 years (interquartile range (IQR), 53-71) at enrolment and 93% were women. Median sCD163 was 3.43 mg/L (IQR 2.48-5.35) and median sMR was 0.35 mg/L (IQR 0.28-0.45). There was an increase in sCD163 and sMR with increasing alkaline phosphatase. Two hundred and one patients were followed for a median of 8.6 years, and sCD163 and sMR predicted long-term risk of liver-related death or LT in univariate analyses, while sCD163 was also associated with outcome after confounder adjusting (adjusted HR = 1.14, 95% CI 1.00-1.30). Finally, we showed an increase in the prediction accuracy of poor outcome by adding sCD163 to the UK-PBC risk score. CONCLUSION: The macrophage activation markers sCD163 and sMR represent a non-invasive measure of PBC disease severity that provides useful long-term prognostic information.
INTRODUCTION: In primary biliary cholangitis (PBC), macrophages are involved in liver inflammation and fibrosis. The macrophage activation markers, soluble (s)CD163 and mannose receptor (sMR) are associated with liver disease severity and prognosis in other chronic liver diseases. We aimed to investigate sCD163 and sMR in patients with PBC. METHODS: We investigated PBCpatients from the Italian PBC Study Group cohort and measured macrophage activation markers in serum at study enrolment. Patients were followed from enrolment until they experienced an event or were censored at their last visit. Events were defined as follows: (a) death from a liver-related cause; or (b) liver transplantation (LT) for PBC. We used Cox regression to investigate the association between sCD163 and sMR and long-term prognosis. RESULTS: In total, 202 PBCpatients were included. Median age was 62 years (interquartile range (IQR), 53-71) at enrolment and 93% were women. Median sCD163 was 3.43 mg/L (IQR 2.48-5.35) and median sMR was 0.35 mg/L (IQR 0.28-0.45). There was an increase in sCD163 and sMR with increasing alkaline phosphatase. Two hundred and one patients were followed for a median of 8.6 years, and sCD163 and sMR predicted long-term risk of liver-related death or LT in univariate analyses, while sCD163 was also associated with outcome after confounder adjusting (adjusted HR = 1.14, 95% CI 1.00-1.30). Finally, we showed an increase in the prediction accuracy of poor outcome by adding sCD163 to the UK-PBC risk score. CONCLUSION: The macrophage activation markers sCD163 and sMR represent a non-invasive measure of PBC disease severity that provides useful long-term prognostic information.
Authors: David E J Jones; Aaron Wetten; Ben Barron-Millar; Laura Ogle; George Mells; Steven Flack; Richard Sandford; John Kirby; Jeremy Palmer; Sophie Brotherston; Laura Jopson; John Brain; Graham R Smith; Steve Rushton; Rebecca Jones; Simon Rushbrook; Douglas Thorburn; Stephen D Ryder; Gideon Hirschfield; Jessica K Dyson Journal: EBioMedicine Date: 2022-05-21 Impact factor: 11.205
Authors: Rasmus Hvidbjerg Gantzel; Mikkel Breinholt Kjær; Tea Lund Laursen; Konstantin Kazankov; Jacob George; Holger Jon Møller; Henning Grønbæk Journal: Front Med (Lausanne) Date: 2021-01-08
Authors: Lars Bossen; Mette Vesterhus; Johannes R Hov; Martti Färkkilä; William M Rosenberg; Holger J Møller; Kirsten M Boberg; Tom H Karlsen; Henning Grønbæk Journal: Clin Transl Gastroenterol Date: 2021-03-01 Impact factor: 4.396
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