Tenofovir-based combination therapy or monotherapy for multi-drug resistant chronic hepatitis B: Long-term data from a multicenter cohort study.

The treatment of multidrug resistant (MDR) chronic hepatitis B (CHB) is challenging. Herein, we report a multicenter prospective cohort study for the evaluation of tenofovir disoproxil fumarate (TDF)-based therapy for MDR CHB in a real-life setting. The inclusion criteria comprised patients with resistance to more than two nucleos(t)ide analogue (NA) classes and hepatitis B virus (HBV) DNA level of ≥200 IU/mL. The primary end-point was virologic response (VR), defined as undetectable HBV DNA (<20 IU/mL) after 60 months. A total of 236 patients met the inclusion criteria. The mean HBV DNA level was 4.16±1.44 log IU/mL; 26.7% of patients had liver cirrhosis. Before the initiation of TDF, 33.5%, 44.9%, and 21.6% of patients had mutations resistant to L-NA+adefovir, L-NA+entecavir (ETV), and L-NA+adefovir+ETV, respectively. A total of 184 patients received TDF-based combination therapy [TDF+ETV (n=178) or TDF+L-NA (n=6)], and 52 patients received TDF monotherapy. In the entire cohort, the VR rates were 77.2%, 89.9%, and 92.2% at 12, 36, and 60 months, respectively. The VR rates were not significantly different between the combination therapy and the monotherapy group after 12 (76.2% vs. 80.4%, P=0.533), 36 (89.8% vs. 90.3%, P=1.000), or 60 (92.9% vs. 87.5%, P=0.499) months. Also there was no significant difference in the cumulative VR rates for 5 years between the treatment groups (P=0.910). Newly developed antiviral resistance was not observed.TDF-based therapy was effective for the treatment of MDR CHB. The efficacy of TDF monotherapy was not different from that of the TDF-based combination therapy.