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Thromb Haemost
DOI: 10.1055/a-2615-4682
Coagulation and Fibrinolysis

Association of Fibrinogen Variants with Severity of Obesity and Metabolic Liver Disease: 2-Year Follow-up after Bariatric Surgery

Nadja B. Pedersen 
1   Unit for Thrombosis Research, Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark
2   Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
,
Anna-Marie Bloch Münster
1   Unit for Thrombosis Research, Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark
2   Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
,
Mette Munk Lauridsen
2   Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
3   Department of Gastroenterology and Hepatology, Liver Research Group, University Hospital of Southern Denmark, Esbjerg, Denmark
,
Yaseelan Palarasah
1   Unit for Thrombosis Research, Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark
4   Department of Cancer and Inflammation Research, University of Southern Denmark, Odense, Denmark
,
Charlotte W. Wernberg
2   Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
3   Department of Gastroenterology and Hepatology, Liver Research Group, University Hospital of Southern Denmark, Esbjerg, Denmark
,
Lea Ladegaard Grønkjær
2   Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
3   Department of Gastroenterology and Hepatology, Liver Research Group, University Hospital of Southern Denmark, Esbjerg, Denmark
,
Birgitte G. Jacobsen
3   Department of Gastroenterology and Hepatology, Liver Research Group, University Hospital of Southern Denmark, Esbjerg, Denmark
,
Elise Jonasson
2   Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
3   Department of Gastroenterology and Hepatology, Liver Research Group, University Hospital of Southern Denmark, Esbjerg, Denmark
,
Moniek P.M. de Maat 
1   Unit for Thrombosis Research, Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark
2   Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
5   Department of Hematology, Cardiovascular Institute, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
,
Else-Marie Bladbjerg 
1   Unit for Thrombosis Research, Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark
2   Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
› Author Affiliations
Funding This research was supported by the Department of Regional Health Research, the University of Southern Denmark, the Region of Southern Denmark, and the Danish National Research Foundation. The funding sources were not involved in the study.
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Abstract

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 body mass index (BMI) > 35 kg/m2. A subgroup of 93 individuals, who underwent bariatric surgery (n = 35) or served as nonsurgical control group (n = 58), were followed for 2 years. Hepatic tissue samples were scored for MASLD and fibrosis. Fibrinogen variants were measured using enzyme-linked immunosorbent assay.

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% confidence interval: −19, 160] µg/mL; ΔαE: 0.85 [−0.36, 2.06] µg/mL; Δsialylated: 0.09 [−0.05, 0.24] arbitrary units [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] %), whereas 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.

Keywords

steatotic liver - fibrin - fibrosis - inflammation

Supplementary Material



Publication History

Received: 20 January 2025

Accepted: 18 May 2025

Accepted Manuscript online:
19 May 2025

Article published online:
05 June 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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