Objective: Natural killer cells (NK)-expressing TRAIL have capacityto mediate hepatocyte apoptosis in HBeAg-negative chronic hepatitisB (CHB) patients with liver flare; however,it remains unknown thatthe characteristics of NK TRAIL in HBeAg-positive CHB patients.Methods: Peripheral blood was obtained from 18 HBeAg+ CHBpatients with high levels of ALT (IA),16 of immune tolerant (IT)subjects and 18 healthy controls (HC).TRAIL expression by NKcells was examined by using flow cytometry.We also analyzed thecorrelation between TRAIL expression and NK cytolytic activity inthese patients.Finally,the influence of IFN-α on TRAIL expressionwas detected both in vitro and in vivo.Results: TRAIL expression by peripheral NK cells,especiallyCD56bright NK subsets,was significantly increased in IA patientsas compared with IT and HC subjects.More importantly,increasedTRAIL expression on CD56bright population was found to bepositively correlated with increased ALT level.The cytolyticactivity of NK cells against HepG2 or HepG2.2.15 cells was moresignificantly in IA patients than IT or HC groups; blocking TRAILpathway can reduce target cell death.Finally,IFN-α treatment canincrease TRAIL expression on NK cells both in vitro and in vivo.Conclusions: These data indicated that TRAIL up-regulation on NKcells may be associated with liver injury in HBeAg+ CHB patients.IFN-α treatment can increase TRAIL expressing NK cells in vivo,thus boosting the immune function of NK cells.