Dengue with liver involvement is associated with serum soluble thrombomodulin and P-selectin levels.

Background: The pathogenesis of liver damage in dengue patients has not been clarified. In this study, we sought to identify the factors that are associated with dengue-induced liver damage and evaluate the associations of cytokines/chemokines, including platelets, neutrophils, activated endothelial cells and other inflammatory factors, with liver damage.

Methods: We collected and analysed clinical data from 106 hospitalized dengue patients and evaluated the serum levels of platelet (soluble P-selectin [sP-selectin] and soluble CD40 ligand [sCD40L]), neutrophil (neutrophil elastase [NE] and neutrophil myeloperoxidase [MPO]) and endothelial cell (soluble thrombomodulin [sTM]) activation markers, as well as inflammatory mediators, including C-X-C motif chemokine ligand 2 (CXCL2), interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor-α and interferon-γ (which are associated with liver damage), in 32 patients.

Results: In total, 106 dengue patients were included in this study. The patients were categorized into dengue with warning signs (DwWS), dengue without warning signs (DwoWS) and severe dengue (SD). Twenty-four patients (22%) had DwWS and 1 patient (1%) had SD. Compared with the DwoWS group, the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase levels in the DwWS/SD group were significantly greater (p<0.001, p<0.001 and p=0.001, respectively). A long time to onset (odds ratio [OR] 1.495 [95% confidence interval {CI} 1.063 to 2.101], p=0.021), thrombocytopenia (OR 4.166 [95% CI 1.11 to 15.629], p=0.034) and concomitant fatty liver (OR 6.326 [95% CI 1.57 to 25.493], p=0.009) were risk factors for dengue-related liver dysfunction. Compared with patients with normal liver enzyme levels, serum sP-selectin levels were significantly lower (p=0.012), sTM levels were higher (p=0.047), serum ALT and AST levels were positively correlated with sTM (r=0.411, p=0.02 and r=0.419, p=0.039; respectively) and AST levels were negatively correlated with sP-selectin levels (r=-0.441, p=0.011) in dengue patients.

Conclusions: Dengue fever with hepatic involvement is related to serum sTM and sP-selectin levels, thus suggesting that platelet and endothelial cell activation may be involved in the pathogenesis of liver damage and can be used as early predictors of dengue liver damage.