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

Abstract

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.To investigate associations of fibrinogen variants (fibrinogen γ', fibrinogen α_E, and sialylated fibrinogen) with obesity, MASLD, and fibrosis severity and examine changes in variants 2 years after bariatric surgery.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.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; Δα_E: 0.85 [-0.36, 2.06] µg/mL; Δsialylated: 0.09 [-0.05, 0.24] arbitrary units [AU]). Absolute and relative fibrinogen α_E levels increased with MASLD (Δα_E: 2.04 [0.74, 3.35] µg/mL; Δα_E ratio: 0.05 [0.02, 0.08] %) and fibrosis (Δα_E: 1.79 [0.48, 3.11] µg/mL; Δα_E 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] %; Δα_E: 0.03 [0.001, 0.06] %; Δsialylated: 0.02 [0.002, 0.04] AU/g/L) compared with the control group.Obesity, MASLD, and fibrosis alter fibrinogen variant profiles in plasma suggesting that fibrinogen variation plays a role in these inflammatory conditions.