Konstantin Kazankov1, Francisco Barrera2,3, Holger Jon Møller4, Chiara Rosso5, Elisabetta Bugianesi5, Ezio David6, Ramy Younes5, Saeed Esmaili2, Mohammed Eslam2, Duncan McLeod7, Bo Martin Bibby8, Hendrik Vilstrup9, Jacob George2, Henning Grønbaek9. 1. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. konskaza@rm.dk. 2. The Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, Australia. 3. Department of Gastroenterology, Pontificia Universidad Católica, Santiago, Chile. 4. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. 5. Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Torino, Torino, Italy. 6. Division of Pathology, Department of Medical Sciences, University of Torino, Torino, Italy. 7. Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, NSW, Australia. 8. Department of Biostatistics, Aarhus University, Aarhus, Denmark. 9. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Abstract
BACKGROUND & AIMS: Macrophage activation plays a key pathogenic role in experimental non-alcoholic fatty liver disease (NAFLD) and contributes to the progression of steatohepatitis (NASH) and fibrosis. We studied macrophage activation in human NAFLD by measuring soluble (s)CD163, a specific macrophage activation marker, hypothesizing that sCD163 would be associated with the patients' morphological disease grade. Furthermore, we investigated an association between sCD163 and the apoptosis marker cytokeratin-18 (CK-18) to explore a link between macrophage activation and apoptosis. METHODS: sCD163 associations with biochemical and histological measures of NAFLD were investigated in two independent cohorts of 157 Australian and 174 Italian NAFLD patients, with liver biopsies graded for NAFLD severity, steatosis and fibrosis. sCD163 and CK-18 were measured by enzyme-linked immunosorbent assay. RESULTS: In both cohorts sCD163 increased in parallel with the patients' morphological disease grading, being independently associated with the Kleiner fibrosis score (P < 0.001). A high sCD163 predicted advanced fibrosis {F ≥ 3; Australian cohort: area under receiver-operating characteristics curve 0.77 [95% confidence interval (CI): 0.76-0.87], Italian cohort: 0.80 (95% CI: 0.72-0.88)}. In both groups, sCD163 was independently associated with CK-18 (P < 0.001). CONCLUSION: Soluble CD163 reflecting macrophage activation is associated with morphological features of NAFLD suggesting their involvement in the pathogenesis of NAFLD, NASH and particularly fibrosis. An independent association between sCD163 and cytokeratin-18 suggests that apoptosis may contribute to macrophage activation in NAFLD/NASH.
BACKGROUND & AIMS: Macrophage activation plays a key pathogenic role in experimental non-alcoholic fatty liver disease (NAFLD) and contributes to the progression of steatohepatitis (NASH) and fibrosis. We studied macrophage activation in human NAFLD by measuring soluble (s)CD163, a specific macrophage activation marker, hypothesizing that sCD163 would be associated with the patients' morphological disease grade. Furthermore, we investigated an association between sCD163 and the apoptosis marker cytokeratin-18 (CK-18) to explore a link between macrophage activation and apoptosis. METHODS: sCD163 associations with biochemical and histological measures of NAFLD were investigated in two independent cohorts of 157 Australian and 174 Italian NAFLD patients, with liver biopsies graded for NAFLD severity, steatosis and fibrosis. sCD163 and CK-18 were measured by enzyme-linked immunosorbent assay. RESULTS: In both cohorts sCD163 increased in parallel with the patients' morphological disease grading, being independently associated with the Kleiner fibrosis score (P < 0.001). A high sCD163 predicted advanced fibrosis {F ≥ 3; Australian cohort: area under receiver-operating characteristics curve 0.77 [95% confidence interval (CI): 0.76-0.87], Italian cohort: 0.80 (95% CI: 0.72-0.88)}. In both groups, sCD163 was independently associated with CK-18 (P < 0.001). CONCLUSION: Soluble CD163 reflecting macrophage activation is associated with morphological features of NAFLD suggesting their involvement in the pathogenesis of NAFLD, NASH and particularly fibrosis. An independent association between sCD163 and cytokeratin-18 suggests that apoptosis may contribute to macrophage activation in NAFLD/NASH.
Authors: Victoria Cairoli; Elena De Matteo; Paola Casciato; Beatriz Ameigeiras; María Victoria Preciado; Pamela Valva Journal: PLoS One Date: 2022-07-07 Impact factor: 3.752
Authors: Vanessa El Kamari; Corrilynn O Hileman; Pierre M Gholam; Manjusha Kulkarni; Nicholas Funderburg; Grace A McComsey Journal: Clin Gastroenterol Hepatol Date: 2018-06-14 Impact factor: 11.382
Authors: Karen L Thomsen; Francis P Robertson; Peter Holland-Fischer; Brian R Davidson; Rajeshwar P Mookerjee; Holger J Møller; Rajiv Jalan; Henning Grønbæk Journal: J Clin Exp Hepatol Date: 2018-10-05
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: 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