CD163 as a valuable diagnostic and prognostic biomarker of sepsis-associated hemophagocytic lymphohistiocytosis in critically ill children

Objective To investigate CD163 as an effective biomarker for identifying and predicting the outcomes of sepsis-associated hemophagocytic lymphohistiocytosis (SAHS) in children. Methods We prospectively enrolled presumed sepsis patients who had developed prolonged fever (>7 days), hepatosplenomegaly, cytopenias, and hyperferritinemia (>500 ng/mL) despite antibiotic therapy. Blood samples were collected within 24 hours after enrolment. A nested case-control study was performed. The number of patients who fulfilled the HLH-2004 criteria, 28-day mortality outcomes, and 90-day mortality outcomes were recorded. Results Sixty-nine patients were enrolled in the study. Significant increases in the levels of ferritin and soluble CD163 (sCD163) and the percentage of CD163-positive peripheral blood mononuclear cells (mCD163) and decreases in fibrinogen levels and the percentage of natural killer cells (NK %) were observed in patients with SAHS (n = 23) compared with those of patients with sepsis (n = 46). The area under the ROC curve (AUC) for ferritin combined with sCD163 was superior to the AUC for either ferritin or sCD163 for distinguishing SAHS from sepsis. Moreover, sCD163 was a prognostic factor for 28-day mortality (0.857 [0.659-1.000]). Conclusions sCD163 is a valuable biomarker for the differential diagnosis of SAHS from sepsis and effectively predicts 28-day mortality in children with SAHS.