Background: The pathogenesis of HBV-related acute-on-chronic liver failure (HBV-ACLF) is mainly based on a heightened immune-inflammatory reaction; however, the intimate underlying mechanism remains unclear.Objectives: The aim of the study was to explore potential key immune molecular targets that could serve as early predictive markers for HBV-ACLF.Patients and Methods: Twenty-seven patients with acute exacerbation of chronic hepatitis B (CHB) (defined by: alanine transaminase ³20 ULN, total bilirubin ³5 ULN, 40%< prothrombin time activity £ 60%) and without cirrhosis were divided into 18 cases which did not progress to HBV-ACLF (defined by: prothrombin time activity < 40% and development within four weeks of hepatic encephalopathy and/or ASCITES) and nine cases that developed HBV-ACLF. Nine healthy people defined the normal control group (NC). Interleukin-1b (IL-1b), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, TNF-a and IFN-g protein levels were assayed by Cytometric Bead Array (CBA) in blood plasma. The ELISA method was applied to confirm IL-10 detection using the CBA method.Results: IL-4, IL-12p70 and IFN-g were undetectable; IL-1b, IL-6, IL-8, IL-10 and TNF-a levels were significantly higher than in NC. Moreover, cytokines reached the highest levels in acute exacerbation of CHB, with the exception of IL-2 and IL-8. When comparing the HBV-ACLF patients prior to and at the time of ACLF diagnosis, IL-10 was the only cytokine that exhibited a significant decrease (P=0.008). IL-10 concentrations were positively correlated to ALT levels (r=0.711, P<0.001).Conclusions: The assessment of plasma IL-10 levels in chronic hepatitis B acute exacerbation may provide an early predictive marker for progression to HBV-ACLF.