METABOLIC dysfunction-associated steatotic liver disease (MASLD) is a liver condition closely linked to obesity, representing its hepatic manifestation. While animal studies have previously suggested a connection between variations in fibrinogen, a key blood protein involved in clotting and inflammation, and obesity-related liver disease, its role in humans remains unclear.
A recent study involving 195 individuals with a body mass index (BMI) over 35 kg/m² investigated how different naturally occurring fibrinogen variants relate to obesity, MASLD, and liver fibrosis severity. The study focused on three fibrinogen variants: fibrinogen γ’, fibrinogen αE, and sialylated fibrinogen. A subgroup of 93 participants was followed for two years, including those who underwent bariatric surgery and others who did not.
The findings showed that individuals with higher BMI (>45 kg/m²) tended to have increased levels of fibrinogen variants compared to those with BMI under 40 kg/m². Specifically, fibrinogen αE levels, both absolute and relative, were higher in patients with MASLD and those with more severe liver fibrosis. Conversely, relative levels of fibrinogen γ’ decreased with worsening fibrosis.
Following bariatric surgery, patients exhibited a notable decrease in sialylated fibrinogen levels, while the relative levels of all three fibrinogen variants increased compared to non-surgical controls. These changes indicate a complex relationship between fibrinogen variants and metabolic and inflammatory processes in obesity-related liver disease.
This study highlights the potential role of fibrinogen variation in the pathophysiology of MASLD and liver fibrosis. Understanding these associations could open avenues for better biomarkers and targeted therapies for liver disease in obese patients, especially in the context of surgical interventions like bariatric surgery.
Reference
Bødker Pedersen N et al. Association of fibrinogen variants with severity of obesity and metabolic liver disease: 2-year follow-up after bariatric surgery. Thromb Haemost. Published online May 19, 2025. doi:10.1055/a-2615-4682
