BACKGROUND:Chronic hepatitis B virus (HBV) infection is a major cause of liver ifbrosis, but the mechanisms underlying HBV-related ifbrogenesis are still unknown. Although the roles of HBV X protein (HBx) remain poorly understood, it is thought to play an important role in the regulation of cellular growth and hepatocarcinogenesis. The aim of this study was to determine the role of HBx in liver ifbrogenesis by studying the effect of HBx on the proliferation and expression of ifbrosis-related molecules in the human hepatic stellate cell line, LX-2. METHODS:We established anin vitro co-culture system with LX-2 cells and a stable QSG7701-HBx cell line which had been transfected with the HBx gene.3H-TdR incorporation and lfow cytometry were used to determine the effects of HBx on the proliferation of LX-2 cells.α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), transforming growth factor-β receptorⅡ (TGF-βRⅡ), and connective tissue growth factor (CTGF) in LX-2 cells were analyzed by Western blotting. In addition, the expression levels of collagen typeⅠ (ColⅠ) from the co-cultured media were measured by ELISA. RESULTS:3H-TdR incorporation increased signiifcantly in LX-2 cells co-cultured with QSG7701-HBx cells compared to those cultured with QSG7701-pcDNA3 and QSG7701 (non-tumorigenic human liver cell line). Cell cycle results revealed that HBx accelerated the progression of G1 to S in LX-2 cells. The expressions ofα-SMA, TGF-β1, TGF-βRⅡ, CTGF and ColⅠ were signiifcantly increased in the co-cultures of LX-2 cells with stable QSG7701-HBx cells.CONCLUSION:These results suggest that HBx may facilitate liver ifbrosis by promoting hepatic stellate cell proliferation and upregulating the expression of ifbrosis-related molecules.