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Background and Aims:Recent accumulating evidence indi-cates the biological actions of autotaxin (ATX) in liver disease. However, the relationship between ATX and liver failure has not been reported. The present study aimed to examine altera-tions of serum ATX in acute-on-chronic liver failure (ACLF) and evaluate whether serum ATX could be useful as an early wing biomarker of ACLF. Methods:Serum ATX was meas-ured in 50 patients with hepatitis B-related ACLF, 14 patients with alcohol-related ACLF, 11 patients with hepatitis B-related pre-ACLF, 11 patients with alcohol-related Child-Pugh A cirrho-sis, 39 patients with hepatitis B-related Child-Pugh A cirrhosis, 26 patients with chronic hepatitis B, and 38 healthy volunteers by enzyme-linked immunosorbent assay. Results:Serum ATX level was significantly higher in the pre-ACLF group than in the Child-Pugh A cirrhosis and chronic hepatitis B groups but lower than in the ACLF group; furthermore, patients with pre-ACLF deteriorated to ACLF had significantly higher serum ATX levels than pre-ACLF patients that did not progress to ACLF. Serum ATX levels were significantly higher among male ACLF patients with preclinical infection, spontaneous bacterial peritonitis or pneumonia, as compared to patients with ACLF but no sponta-neous bacterial peritonitis or pneumonia. Serum ATX levels were well correlated with serum biochemical parameters of liver function and model for end-stage liver disease score. Se-rum ATX$584.1 ng/mL was a poor prognostic factor for ACLF (hazard ratio of 4.750, 95％ confidence interval of 1.106-20.392, p=0.036). Conclusions: Serum ATX level may be a useful early wing biomarker for ACLF.