Abstract: Objective To analyze the HBV biological changes pre- and post-clinical exacerbation in an acute-on-chronic liver failure patient caused by HBV YMDD mutation. Methods Two HBV replication competent clones were constructed which contained 1.3 copies of HBV genome and represented the dominant quasispecies before and after clinical exacerbation. Then，they were transfected into Huh-7 cells，and HBsAg and HBeAg in culture supernant were examinanted by ELISA. HBV transcripts in transfected cells was semi-quantified by reverse transcriptional quantified PCR. At the same time，they were employed by hydrodynamic injection into BALB/c mice to establish HBV acute infected model，and the viremia were checked by real-time quantified PCR. Results A series of mutations were observed in all four open reading frames of HBV besides YVDD mutation in YMDD motif after clinical exacerbation. The levels of HBsAg in the supernant of wild and mutant HBV replication competent clones transfected Huh-7 cells were not significantly different（P＞0.05），while HbeAg secretion stopped（P＜0.01）；The HBV transcripts in transfected cells were unchanged（P＞0.05）；The HBV viremia titer（7.24±0.63 and 6.86±0.62lg copies/ml）were comparable between the two clones（P＞0.05）. Conclusion There is no significant change in biological characteristics between the HBV clones pre-and post-clinical exacerbation caused by YMDD mutation，except for the defect of HBeAg secretion competence. The mutations locates in the non-reverse transcriptase domain may play some important roles in compensating the viral replication competence.

Key words: Hepatitis B virus, Liver failure, YMDD Mutation