At the 2024 AASLD Annual Meeting, Dr. Qing Xie's team from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, presented findings on the efficacy and safety of a novel tenofovir derivative, tenofovir amibufenamide (TMF), in ALT-normal chronic HBV patients. The PROMOTE study, the first large-scale, multicenter, randomized controlled trial targeting this patient population, showed TMF significantly improved virological response rates, effectively reduced HBV DNA, HBsAg, and ALT levels, and demonstrated favorable safety. These findings offer new treatment options and high-quality evidence supporting the necessity of therapy for ALT-normal chronic HBV patients.The PROMOTE study (NCT05797714) is a prospective, multicenter, randomized, open-label, controlled trial involving 12 centers, including Ruijin Hospital. It assessed the efficacy and safety of TMF in ALT-normal chronic HBV patients (ALT <40 IU/L) compared to a control group without antiviral therapy. A total of 197 participants were enrolled, with 95 in the TMF group and 102 in the control group, followed for up to 144 weeks.
In the TMF group, patients received TMF, with the option to add entecavir after 96 weeks if HBV DNA remained above 20 IU/mL. The control group was monitored, and TMF was initiated if disease progression occurred. The primary endpoint was the proportion of patients achieving HBV DNA <20 IU/mL at 48 weeks.
Key results showed that the TMF group had a significantly higher proportion of patients achieving HBV DNA <20 IU/mL compared to controls (74.2% vs. 9.0%, P<0.001). The TMF group also demonstrated greater median reductions in HBV DNA and HBsAg levels compared to controls. Additionally, TMF reduced the proportion of patients with high-normal ALT levels, increasing the proportion with low-normal ALT levels. No significant differences in safety parameters were observed between the two groups.
These midterm findings suggest that TMF significantly enhances virological response in ALT-normal chronic HBV patients, effectively lowering HBV DNA, HBsAg, and ALT levels while maintaining good safety profiles for bone, kidney, and lipid health. The upcoming 96-week and 144-week results are expected to further confirm these benefits and provide evidence for the necessity of antiviral therapy in this patient population. The study highlights the potential of nucleos(t)ide analogs in revolutionizing the management of ALT-normal chronic HBV infection.
