Efficacy of TDF, TAF, TMF, and TDF-to-TAF switch in chronic hepatitis B: a network meta-analysis

Abstract

Objective: We compared the efficacy of four treatment strategies for chronic hepatitis B (CHB): tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), tenofovir amibufenamide (TMF), and TDF-to-TAF switch strategies strategy. We conducted a network meta-analysis to provide evidence-based clinical guidance. Methods: We systematically retrieved PubMed, Web of Science, Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) databases up to April 2025 for randomized controlled trials (RCTs) and cohort studies. We assessed literature quality using the Cochrane Risk of Bias (ROB) tool and Newcastle-Ottawa Scale (NOS). Stata 17 was employed for network meta-analysis, focusing on virological response rate, hepatitis B surface antigen (HBsAg) clearance rate, hepatitis B e antigen (HBeAg) clearance rate, and alanine aminotransferase (ALT) normalization rate. Results: Virological response did not differ between TMF monotherapy and TDF-to-TAF switch (OR = -0.03; 95% CI -0.42 to 0.36). HBsAg clearance was similar between TAF and TMF (95% CI: -1.17-1.14). For the rate of HBeAg loss, both TAF and TMF exhibited favorable therapeutic effects. For ALT normalization rate, TMF monotherapy was the most effective, with an average effect size of 0.11 (95% CI: -0.14-0.37), while TDF monotherapy was generally inferior to the other three treatment strategies. Conclusion: Our findings may help guide the selection of individualized CHB treatment strategies. However, given the limited evidence and potential bias, these results are preliminary and must be interpreted with caution. For regimens such as TMF that lack robust data, well-established alternatives should be preferred. Long-term, multi-endpoint studies are required to confirm both efficacy and safety before routine clinical adoption.