A different inhibitor is required for overcoming entecavir resistance: a comparison of four rescue therapies in a retrospective study

Aims

Little clinical data are available regarding re‐establishing the effective inhibition of entecavir (ETV)‐resistant mutants. In this retrospective study, we aimed to compare the efficacies of four treatment regimens as rescue therapy for those chronic hepatitis B (CHB) patients with ETV resistance.

Methods

A total of 65 patients with ETV resistance were assigned either with tenofovir disoproxil fumarate (TDF) monotherapy (n = 21), ETV (0.5 mg) plus adefovir (ADV) combination therapy (n = 19), ETV (1.0 mg) monotherapy (n = 11) or ETV (0.5 mg) plus TDF combination therapy (n = 14). The efficacy and safety of four treatment regimens were compared.

Results

There were no significant differences among the four study groups in baseline characteristics, including HBV DNA levels (χ² = 0.749, P = 0.862) and hepatitis B e antigen‐positivity (χ² = 0.099, P = 0.992). The median reduction in serum HBV DNA level from baseline at week 48 was −2.37 ± 1.07 log₁₀ IU ml⁻¹, −2.16 ± 0.81 log₁₀ IU ml⁻¹, −1.17 ± 1.23 log₁₀ IU ml⁻¹ and −2.49 ± 1.10 log₁₀ IU ml⁻¹, respectively (F = 4.078, P = 0.011). The TDF group and ETV (0.5 mg) + TDF group have the highest undetectable HBV DNA rate (76.19% vs. 78.57%) compared to the ETV (0.5 mg) + ADV group and the ETV (1.0 mg) group (63.16% vs. 18.18%, respectively). Two patients in the ETV (1.0 mg) group experienced virological breakthrough at week 48 and was attributed to poor drug adherence.

Conclusions

TDF monotherapy appeared to deliver the highest undetectable HBV DNA rate in patients with ETV resistance, and ADV plus ETV combination therapy could be another choice for patients with financial restraint.

DOI: 10.1111/bcp.13330

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