Elevated serum level of human epididymal protein 4 (HE4) predicts poor prognosis in the critically ill with sepsis: A prospective observational cohort study

Human epididymal protein 4 (HE4) has been widely used as an important clinical tumor biomarker for epithelial ovarian cancer. HE4 has recently been suggested to be an inflammatory biomarker and we hypothesized that the serum HE4 level upon intensive care unit (ICU) admission might predict prognosis in septic patients. We hypothesized that serum HE4 level upon intensive care unit (ICU) admission could predict prognosis in septic patients.Serum levels of HE4, procalcitonin (PCT), C-reactive protein (CRP), IL-6 and IL-8 were quantified, and sequential organ failure assessment (SOFA) scores were recorded on day one of admission to ICU. The area under the receiver operating characteristic (ROC) curve (AUC) analysis of HE4, IL-6, PCT and SOFA at ICU admission for 28-day mortality was used to evaluate the ability of HE4 in predicting 28-day mortality of sepsis. Multivariate regression analysis was used to identify the independent risk factors for 28-day mortality.A total of 1289 patients were recruited, and 117 patients were included for final analysis. On day of ICU admission, septic patients had significantly higher levels of serum HE4 than those with infection without sepsis, those with ovarian cancer, or healthy controls. Compared with septic survivors, septic non-survivors presented with significantly higher serum HE4 concentrations. Serum levels of HE4 correlated with disease severity scores and cytokine levels (IL-6 and IL-8). Upon ICU admission, the AUC for HE4 level association with 28-day mortality was 0.881, higher than the AUC for SOFA (0.713), IL-6 (0.589), and PCT (0.567). A regression analysis showed that HE4 was an independent mortality predictor.HE4 can predict poor prognosis in septic patients, which may help to identify a group of septic patients at high risk of death.