Superior Efficacy of Tenofovir Alafenamide Compared With Entecavir in Reducing Hepatitis B Surface Antigen: A Multicentre Propensity Score‐Matched Study Using Linear Mixed‐Effects Models

BACKGROUND AND AIMS: Entecavir and tenofovir alafenamide fumarate are potent nucleos(t)ide analogues used to treat chronic hepatitis B; however, their differential effects on hepatitis B surface antigen expression decline remain unclear. In this multicentre study, we aimed to examine the hepatitis B surface antigen-reducing effects. METHODS: Treatment-naïve chronic hepatitis B patients who received entecavir (n = 491) or tenofovir alafenamide fumarate (n = 463) were enrolled. After 1:1 propensity score matching for sex, baseline hepatitis B surface antigen, hepatitis B e-antigen status, hepatitis B virus deoxyribonucleic acid, fibrosis-4 score, and the presence of hepatocellular carcinoma, data from 334 patients per group were analysed. Linear mixed-effects models were used to assess longitudinal changes over 4 years. RESULTS: Tenofovir alafenamide fumarate was associated with a greater decline in hepatitis B surface antigen compared to entecavir, with significant differences at 1, 3, and 4 years. Its superiority was most pronounced in patients aged < 65 years, those without cirrhosis, those with baseline hepatitis B surface antigen ≥ 3.0 log IU/mL, those with either negative or positive hepatitis B e-antigen, and those with baseline hepatitis B virus deoxyribonucleic acid < 4.4 log IU/mL. Both treatments achieved comparable virological suppression and alanine aminotransferase normalisation. The estimated glomerular filtration rate showed a transient decline with tenofovir alafenamide fumarate in year 1, which subsequently diminished and may partly reflect the inhibition of tubular creatinine secretion. CONCLUSIONS: This evidence supports personalised treatment selection for functional cure. TRIAL REGISTRATION: The UMIN Clinical Trials Registry 000034362.