Impact of Tenofovir Alafenamide on Lipid Profiles in Chronic Hepatitis B Patients: Systematic Review and Meta‐Analysis

ABSTRACT Tenofovir alafenamide (TAF) is widely used for chronic hepatitis B (CHB) treatment due to its improved renal and bone safety compared to tenofovir disoproxil fumarate (TDF). However, emerging evidence suggests that TAF may adversely affect lipid metabolism, raising concerns about potential cardiovascular risks. A systematic review and meta‐analysis following PRISMA guidelines was conducted. Studies comparing lipid profile changes in CHB patients receiving TAF, TDF, or entecavir (ETV) were retrieved from PubMed, Cochrane, and Embase. Primary outcomes included changes in total cholesterol (TC), triglycerides (TG), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL). Sensitivity analyses were performed to assess potential confounders, including lipid‐lowering therapy. Trial sequential analysis (TSA) was used to evaluate the sufficiency of evidence. A total of 23 studies (5 RCTs, 18 observational) were included. Observational data showed significant increases in TC (MD = 10.74 mg/dL), TG (MD = 11.56 mg/dL), LDL (MD = 3.08 mg/dL), and HDL (MD = 7.51 mg/dL) with TAF versus TDF. Meta‐analysis of RCTs confirmed these findings, showing TC (MD = 18.28 mg/dL), LDL (MD = 13.09 mg/dL), and HDL (MD = 4.95 mg/dL) elevations. TAF is associated with increased lipid levels, likely due to the loss of TDF's lipid‐lowering effect. While its cardiovascular risk remains uncertain, clinicians should monitor lipid profiles in CHB patients on TAF, particularly those at high cardiovascular risk.