Regulation of hepatitis B virus (HBV) transcription-related factors and HBV replication. A, Overexpression of HBV proteins (precore/core [pre-C/C], pre-S/S, pol, and HBV x [HBx]) and HBV transcription-related factors (LRH1, PPARA, and HNF4A) in HepG2 cells. B, Establishment of HepAD38 cells overexpressing LRH1 (ie, HepAD38-LRH1 cells). C, Time course (until 18 days) of HBV DNA, pregenomic RNA, and cccDNA levels in HepAD38-LRH1 cells and HepAD38 cells with or without entecavir (ETV). D, Effect of metformin (Met) on HBV transcription-related factors (LRH1, PPARA, and HNF4A) in HepAD38 cells and primary human hepatocytes (PHHs). The experiments were repeated 3 times (A, B and D) or performed in triplicate and repeated 3 times. *P < .05, **P < .01, and ***P < .001.