PB0179 - The association of metabolic dysfunction-associated steatotic liver disease with fibrinogen splice variants in patients with severe obesity: effects of weight-loss surgery

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the hepatic manifestation of obesity with a disease spectrum ranging from simple hepatic steatosis to metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis and cirrhosis, and hepatocellular carcinoma. The central protein in the coagulation cascade, fibrinogen, has a well-documented association with risk of inflammatory disease and is increased in individuals with obesity. In humans, there is a large number of post-translational modifications and genetic variations of fibrinogen. Two common, naturally occurring splice variants are fibrinogen γ’ with a 20 amino acid extension of the γ-chain and fibrinogen αE with a 236 amino acid extension of the α-chain constituting 10-15% and 1-2% of total fibrinogen in blood, respectively. The biochemical properties of both splice variants vary from the common isoforms, resulting in clots with thinner fibrin fibers and denser fibrin networks. A study in mice links the fibrinogen variant, Fibγ390-396A with obesity based on its ability to bind leucocytes, but how fibrinogen variants are associated with obesity and MASLD in humans are unknown.

Aims: To determine fibrinogen γ’ and fibrinogen αE levels in plasma in a Danish obese population and to investigate how fibrinogen variant concentrations are associated with body mass index (BMI) and MASLD before and two years after weight-loss surgery.

Methods: 120 men and women (BMI >35 kg/m2) who gave informed consent underwent blood sampling and liver biopsy before and two years after weight-loss surgery. MASLD and levels of fibrinogen γ’ and fibrinogen αE are measured in the samples. Fibrinogen isoforms are measured using in-house Enzyme-linked immunosorbent assay (ELISA). MASLD severity is determined by a standardized histological score (Nonalcoholic fatty liver disease (NAFLD) activity score) based on severity of steatosis, hepatocellular ballooning, and lobular inflammation in liver biopsies.

Results: Results will be presented at the ISTH congress.

Conclusion(s): The Danish Research Ethics Committee approved the study.