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Thromb Haemost
DOI: 10.1055/a-2615-4682
Original Article

Association of fibrinogen variants with severity of obesity and metabolic liver disease: 2-year follow-up after bariatric surgery

Nadja Bødker Pedersen 
1   University of Southern Denmark Department of Regional Health Research, Odense, Denmark (Ringgold ID: RIN683580)
,
Anna-Marie B Münster
2   Unit for Thrombosis Research, Department of Clinical Biochemistry - University Hospital of Southern Denmark, Esbjerg, Esbjerg, Denmark
,
Mette Munk Lauridsen
3   Liver Research Group, Department of Gastroenterology and Hepatology - University Hospital of Southern Denmark, Esbjerg, Esbjerg, Denmark
,
Yaseelan Palarasah
4   Department of Cancer & Inflammation Research, University of Southern Denmark, Odense, Denmark (Ringgold ID: RIN6174)
,
Charlotte Wilhelmina Wernberg
5   Liver Research Group, Department of Gastroenterology and Hepatology - University of Southern Denmark, Esbjerg, Esbjerg, Denmark
,
Lea Ladegaard Grønkjær
3   Liver Research Group, Department of Gastroenterology and Hepatology - University Hospital of Southern Denmark, Esbjerg, Esbjerg, Denmark
,
Birgitte Gade Jacobsen
3   Liver Research Group, Department of Gastroenterology and Hepatology - University Hospital of Southern Denmark, Esbjerg, Esbjerg, Denmark
,
Elise Jonasson
3   Liver Research Group, Department of Gastroenterology and Hepatology - University Hospital of Southern Denmark, Esbjerg, Esbjerg, Denmark
,
Moniek de Maat 
6   Hematologie, Erasmus University Medical Center, Rotterdam, Netherlands
,
Else-Marie Bladbjerg 
7   Department of Regional Health Research, University of Southern Denmark, Odense, Denmark (Ringgold ID: RIN6174)
› Author AffiliationsSupported by: Department of Regional Health Research, University of Southern Denmark
Supported by: The Danish National Research Foundation
Supported by: The Region of Southern Denmark

Clinical Trial: Registration number (trial ID): NCT03535142, Trial registry: ClinicalTrials.gov (http://www.clinicaltrials.gov/), Type of Study: Prospective
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Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the hepatic manifestation of obesity. Studies in mice link fibrinogen variation to obesity and MASLD, but how naturally occurring fibrinogen variants associate with obesity and MASLD in humans is unknown. Objectives: To investigate associations of fibrinogen variants (fibrinogen γ’, fibrinogen αE, and sialylated fibrinogen) with obesity, MASLD, and fibrosis severity and examine changes in variants 2 years after bariatric surgery. Methods: We included 195 individuals with a BMI>35 kg/m2. A subgroup of 93 individuals, who underwent bariatric surgery (n=35) or served as non-surgical control group (n=58), were followed for 2 years. Hepatic tissue samples were scored for MASLD and fibrosis. Fibrinogen variants were measured using ELISA. Results: Absolute levels of fibrinogen variants tended to be higher in individuals with BMI>45 kg/m2 compared with BMI<40 kg/m2 (Δγ’: 70 (95% CI -19;160) µg/mL; ΔαE: 0.85 (-0.36;2.06) µg/mL; Δsialylated: 0.09 (-0.05;0.24) AU). Absolute and relative fibrinogen αE levels increased with MASLD (ΔαE: 2.04 (0.74;3.35) µg/mL; ΔαE ratio: 0.05 (0.02;0.08) %) and fibrosis (ΔαE: 1.79 (0.48;3.11) µg/mL; ΔαE ratio: 0.05 (0.02;0.07) %), while relative fibrinogen γ’ levels decreased with fibrosis (Δγ’ ratio: -2.52 (-4.70;-0.35) %). After bariatric surgery, sialylated fibrinogen levels were lower (Δsialylated: -0.22 (-0.32;-0.11) AU), but relative levels of the fibrinogen variants were higher (Δγ’: 1.7 (0.03;3.30) %; ΔαE: 0.03 (0.001;0.06) %; Δsialylated: 0.02 (0.002;0.04) AU/g/L) compared with the control group. Conclusion: Obesity, MASLD, and fibrosis alter fibrinogen variant profiles in plasma suggesting that fibrinogen variation plays a role in these inflammatory conditions.



Publication History

Received: 20 January 2025

Accepted after revision: 18 May 2025

Accepted Manuscript online:
19 May 2025

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