HBE1 and infection: In particular, there are some clinical and virological points which deserve consideration: 1) a non-protective HBsAb titer in high-viremic HBV infection; 2) a difficult-to-treat infection, both with IFN therapy and with NAs (ADV and ADV plus ETV); 3) a strong response to second-generation NAs combination (ETV plus TDV), finally with seroconversion to anti-HBe and HBsAg loss.