Sepsis-associated liver dysfunction confounds the association between circulating PCSK9 concentration and mortality...

Pro-protein convertase subtilisin/kexin 9 (PCSK9) is a potential therapeutic target in sepsis. However, its role as a prognostic biomarker remains unclear. This study investigated the relationship between plasma PCSK9 concentration and mortality in septic patients, focusing on the impact of sepsis-associated liver dysfunction (SALD).

Patients meeting the Sepsis-3 criteria were enrolled. Plasma samples were collected within 24 h of admission. Patients were grouped into tertiles based on PCSK9 concentration and followed up for survival analysis. Further analyses were performed using Cox proportional hazard models and restricted cubic spline curves.

A total 415 of patients were enrolled. Low PCSK9 group exhibited higher 28-day mortality. Among patients with liver sequential organ failure score (SOFA) ≥ 1, PCSK9 concentration displayed an inverse linear correlation with mortality, in contrast to a U-shaped pattern among those with liver SOFA = 0. Adjustment for international normalized ratio and liver SOFA diminished the significance of the association between PCSK9 concentration and mortality in the entire cohort.

The association between low plasma PCSK9 concentration and mortality in sepsis may be influenced by SALD. Further investigations into the role of PCSK9 in sepsis should consider the impact of liver dysfunction on PCSK9 synthesis and prognosis.