Late entecavir resistance after more than 10 years of therapy in a treatment-na�ve patient with chronic hepatitis B genotype D3

Entecavir resistance in nucleos(t)ide-naïve patients with chronic hepatitis B is exceptional because of its high genetic barrier. We report a case of progressive virological breakthrough after more than 10 years of effective entecavir therapy in an apparently treatment-naïve patient with genotype D3 infection. Resistance testing identified classical entecavir resistance mutations (rtL180M/rtM204V/rtT184A) together with concomitant HBsAg escape mutation s132F. Increasing HBV-DNA and qHBsAg levels suggested expansion of resistant viral populations under prolonged antiviral selective pressure. Antiviral therapy was switched to tenofovir.