Y. Wakui 1 , J. Inoue 1 , Y. Ueno 1 , T. Shimosegawa 1 1 Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan Background/aim: Chronic hepatitis B patients are clinically treated with nucleot(s)ide analogues and IFN-. Nucleot(s)ide analogues have problems including drug resistance in continuous treatment, and IFN-has disadvantages of limited effectiveness and side effects. Therefore, novel antiviral drugs are still needed. In this study, the suppressive effect to the replication of HBV was examined in vitro by using bezafibrate and rosiglitazone, which are ligands of peroxisome proliferator activated receptor (PPAR) and , respectively. Methods: The cytotoxicity of bezafibrate and rosiglitazone to HepG2 cells was examined with MTS assay, and the concentration of 50% cytotoxicity (CC50) was calculated. HepG2 cells were transiently transfected with the plasmid containing 1.3-fold HBV genome of a genotype B strain. After 24 hours of transfection, rosiglitazone and bezafibrate was added to the cells. Using the medium at day 3 after the addition of drugs, HBV DNA was quantified with real-time PCR. Results: The CC50 of bezafibrate and rosiglitazone in HepG2 cells were 250 M and 150 M, respectively. The amount of HBV-DNA in the medium was decreased when the density of bezafibrate was over 200 M, but the density demonstrated considerable cytotoxicity. In contrast, rosiglitazone of 5 M, which showed no cytotoxicit, decreased the amount of HBV DNA. The 50% effective concentration (EC50) was calculated to be 9.8 M.