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

Abstract

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 ≥200IU/mL. The primary end-point was virologic response (VR), defined as undetectable HBV DNA (<20IU/mL) after 60months. 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 60months, respectively. The VR rates were not significantly different between the combination therapy and the monotherapy group after 12 (76.2% vs 80.4%, P=.533), 36 (89.8% vs 90.3%, P=1.000) or 60 (92.9% vs 87.5%, P=.499) months. Also, there was no significant difference in the cumulative VR rates for 5years between the treatment groups (P=.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.