Published online Dec 6, 2023. doi: 10.12998/wjcc.v11.i34.8139
Peer-review started: November 10, 2023
First decision: November 22, 2023
Revised: November 23, 2023
Accepted: November 28, 2023
Article in press: November 28, 2023
Published online: December 6, 2023
Processing time: 26 Days and 4.1 Hours
Entecavir (ETV) is a potent and safe antiviral agent for patients with chronic hepatitis B (CHB); however, some patients may exhibit suboptimal response or resistance to ETV. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate.
To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV.
A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia [Hepatitis B virus (HBV) DNA ≥ 20 IU/mL] or partial virologic response (HBV DNA < 20 IU/mL, but detectable) were enrolled in the study. The patients were randomly assigned to either continue ETV (0.5 mg) daily or switch to TAF (25 mg) daily for 48 wk. The primary endpoint was the proportion of patients who achieved a virologic response (HBV DNA level < 20 IU/mL) at week 48. Secondary endpoints included changes in serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-HBe levels, and renal and bone safety parameters.
At week 48, the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group (93.3% vs 66.7%, P = 0.012). The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group (-3.8 vs -2.4 Log10 IU/mL, P < 0.001). The rates of ALT normalization, HBeAg loss, HBeAg seroconversion, and HBsAg loss were not found to significantly differ between the two groups. None of the patients developed genotypic resistance to ETV or TAF. Both drugs were well tolerated, with no serious adverse events or discontinuations caused by adverse events. No significant changes were observed in the estimated glomerular filtration rate, serum creatinine level, or urine protein-to-creatinine ratio in either group. The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group (-0.8% vs -2.1%, P = 0.004; -0.6% vs -1.8%, P = 0.007, respectively).
Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.
Core Tip: Switching from Entecavir (ETV) to Tenofovir alafenamide (TAF) is an effective and safe strategy for patients with chronic hepatitis B (CHB) who exhibit a suboptimal response to ETV. This switch improves virologic response rates and reduces the risk of viral resistance. TAF also demonstrates reduced renal and bone toxicity compared to Tenofovir disoproxil fumarate. This finding highlights the potential benefits of switching to TAF in managing CHB patients with suboptimal response to ETV, providing improved treatment outcomes and minimizing long-term safety concerns.