Nucleos(t)ide analogues (NUC) treatment can reduce the extent of HBV DNA integration in chronic hepatitis B (CHB) patients. However, the mechanism by which NUC reduces HBV integration is unclear. This study investigated the effects of entecavir (ETV), one of the commonly used NUC, on cells with HBV integration. Full genome-length HBV DNA was inserted into HepG2 cell genome using the sleeping beauty transposon system. The resulting cells, named HepG2/SB/HBV, was subjected to ETV treatment. In ETV-treated HepG2/SB/HBV, intracellular HBV DNA was reduced by 2-fold. When treated with ETV, HepG2/SB/HBV had an impaired cell survival (25% reduction in cell proliferation rate when compared with untreated cells
p = 0.043). The median integration frequency in untreated HepG2/SB/HBV was 16 integration sites per 10