Abstract
BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV)-infected patients may exhibit liver fibrosis and other pathological changes despite normal alanine aminotransferase (ALT). This study aimed to assess the efficacy and safety of tenofovir amibufenamide (TMF) in chronic HBV-infected patients with normal ALT levels. METHODS: The ongoing PROMOTE study (NCT05797714) is the first prospective, multicenter, randomized, open-label, blank-controlled clinical trial involving chronic HBV-infected patients with normal ALT levels. Participants were randomized in a 1:1 ratio to receive either TMF (TMF group) or no treatment (blank control group). The primary efficacy endpoint was the proportion of participants achieving HBV DNA levels <20 IU/mL at 48 weeks. RESULTS: A total of 197 participants were enrolled, with 95 in the TMF group and 102 in the blank control group. At 48 weeks, a significantly greater proportion of participants in the TMF group achieved HBV DNA levels <20 IU/mL compared with the control group (74.2% vs. 9.0%, P < 0.001). The TMF group demonstrated more pronounced reductions in HBV DNA (-2.63 vs. -0.22 log(10) IU/mL, P < 0.001), HBsAg (-0.07 vs. -0.04 log(10) IU/mL, P = 0.02), and ALT levels (-14.09% vs. 0%, P = 0.003) compared with the blank control. In the TMF group, the proportion of participants with high-normal ALT levels (20-40 IU/L) was reduced. No significant differences were observed between the groups in creatinine, glomerular filtration rate, bone turnover biomarkers, lipid profiles, or phosphorus levels. CONCLUSIONS: TMF treatment demonstrates significant efficacy in chronic HBV-infected patients with normal ALT levels and shows a favorable safety profile regarding bone, renal, and lipid parameters. The PROMOTE study is ongoing, and further results at 96 and 144 weeks are expected to provide additional insights.