Platelet-Activating Factor Pathway in Women With Metabolic Dysfunction-Associated Steatotic Liver Disease and Obesity

This study aimed to investigate the platelet-activating factor (PAF) pathway in obesity-associated metabolic dysfunction-associated steatotic liver disease (MASLD) by evaluating hepatic expression of the PAF receptor (PAFR) and circulating levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) across different stages of disease severity.

Liver biopsies and blood samples were collected from 64 women with severe obesity undergoing bariatric surgery. Hepatic PAFR mRNA expression was quantified by qRT-PCR, and plasma Lp-PLA2 concentrations were measured using ELISA. Histological evaluation of MASLD and metabolic dysfunction-associated steatohepatitis (MASH) was performed according to established criteria. Associations between biochemical, histological, and molecular parameters were analyzed using appropriate statistical tests.

Hepatic PAFR expression was significantly upregulated in MASLD, with the highest levels observed in patients with MASH. PAFR expression correlated positively with key histological features, including steatosis, lobular inflammation, and hepatocyte ballooning. In contrast, circulating Lp-PLA2 levels did not differ across MASLD stages and showed no correlation with hepatic PAFR expression or with liver injury markers.

The PAF-PAFR axis is upregulated in obesity-associated MASLD and is strongly linked to inflammatory and injury-related histological features, supporting PAFR as a potential therapeutic target. Conversely, plasma Lp-PLA2 does not appear to be a reliable noninvasive biomarker of MASLD severity in women with obesity.