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Objective: To evaluate the serum Prostaglandin E2 (PGE2) level in Acute-on-chronic liver failure (ACLF) and determine its predicative value for infection. Methods: From April 2014 to April 2015, ninety-one patients with hepatitis B virus and ACLF but without infection were enrolled into this prospective study that was carried out at our Hospital. Twenty patients with stable chronic hepatitis B were enrolled from the outpatient department and twenty healthy control subjects without any disease were enrolled from hospital staff. Serum PGE2 levels were determined using ELISA at enrollment. Clinical and laboratory parameters were collected. Receiver operating char-acteristic (ROC) curves were used to determine optimal cut-off values to predict infection. Results: Significantly higher PGE2 levels were found in patients with ACLF in com-parison with healthy controls and patients with stable CHB (P < 0.0001). In ACLF patients, PGE2 levels were significantly higher in patients that eventually developed infection than those without this complication (P < 0.0001). ROC analysis showed that serum PGE2 (area under the ROC curve, 0.83) could predict infection in patients with ACLF with sensitivity of 78.4% and specificity of 81.5% using a threshold of 141 pg/mL. Conclusions: Serum PGE2 is associated with the susceptibility to secondary infections for patients with ACLF. Increased PGE2 serum levels may serve as a potential biomarker for developing infections in ACLF patients.