Comparison of rescue strategies in lamivudine-resistant patients with chronic hepatitis B

Lamivudine (LAM) resistance now poses a major problem in the management of patients with chronic hepatitis B virus (HBV) infection. We retrospectively collected clinical data on chronic HBV-infected patients who had developed LAM resistance under de novo LAM monotherapy and subsequently took nucleos(t)ide analogs as rescue strategy in our hospital. From initiation of rescue therapies to January 2012, incidence of antiviral drug resistance was 23.67%, 18%, 6.94% and 0% (P = 0.007) in the group of switching to adefovir dipivoxil (ADV) monotherapy, switching to entecavir (ETV) monotherapy, adding on ADV and switching to combination of ADV and ETV. At month 12, the median levels of serum HBV DNA were respectively 9300 IU/mL, 4648 IU/mL, 2054 IU/mL and 100 IU/mL (P < 0.001), and the cumulative rates of serum ALT normalization were respectively 75%, 84%, 93% and 100% (P = 0.003). Additionally, the strategy of switching to ADV monotherapy induced more single rtA181T mutations. In conclusion, switching to ADV monotherapy has been widely used in real-world clinical practice in China, however, due to the high incidence of drug resistance, switching to neither ADV nor ETV monotherapy is optimal when LAM resistance occurs; combination of ADV and ETV is most effective, whereas the strategy of adding on ADV is rational for most of LAM-resistant Chinese patients with chronic hepatitis B.

► We simultaneously compare the efficacy among four rescue strategies for lamivudine-resistant chronic hepatitis B. ► Combination of adefovir and entecavir is effective in lamivudine-resistant patients. ► Switching to adefovir monotherapy is widely used in real-world clinical practice in China, in spite of its low efficacy. ► Switching to entecavir monotherapy is not optimal in lamivudine-resistant patients due to the high incidence of resistance.