Association of LVV-Hemorphin-7 with Sepsis and Shock: Roles of Cathepsin D and G in Hemoglobin Metabolism in a Prospective ICU Cohort Study

Background: Sepsis is a leading cause of mortality in intensive care units (ICUs). Cell-free hemoglobin (CFH) released during sepsis interacts with lysosomal enzymes from neutrophils and macrophages. This study aims to examine the association of LVV-hemorphin-7 (LVV-H7), cathepsin D, and cathepsin G with sepsis and shock in ICU patients. Methods: A prospective observational cohort study was conducted in the medical ICU of a tertiary referral hospital in Taiwan. The patients with an acute increasing sequential organ failure assessment (SOFA) score ≥ 2 between 2022 and 2023. Blood samples from 40 healthy controls were obtained from the hospital biobank. CFH metabolites, including LVV-H7 and lysosomal enzyme cathepsin D and cathepsin G, were compared between the sepsis (definite and probable) and non-sepsis (possible sepsis) groups. Multivariate logistic regression analyzed factors associated with sepsis and shock. Results: Among 120 patients, 75 were classified as septic and 45 as non-septic. Significant differences were observed in CFH, cathepsin D, cathepsin G, and LVV-H7 levels between sepsis and non-sepsis groups. LVV-H7 was a significant predictor for sepsis (adjusted OR [aOR] 1.009, 95% CI 1.005–1.013; p < 0.001) and shock (aOR 1.005, 95% CI 1.002–1.008; p < 0.05). Cathepsin G predicted non-shock (aOR 0.917, 95% CI 0.848–0.991; p < 0.05), while cathepsin D predicted septic shock (aOR 1.001, 95% CI 1.000–1.002; p < 0.05). Conclusions: LVV-H7, cathepsin D, and cathepsin G are associated with the classification of sepsis and shock episodes in critically ill patients with elevated SOFA scores.