Greater Reductions in Hepatitis B Core-Related Antigen Associated with Switching from Entecavir to Tenofovir Alafenamide Compared with Continued Entecavir Therapy: A Retrospective Observational Study

Background/Objectives: Hepatitis B core-related antigen (HBcrAg) is a surrogate marker that reflects the transcriptional activity of covalently closed circular DNA (cccDNA). However, the impact of switching nucleos(t)ide analogs on HBcrAg levels remains unclear. The current study evaluated changes in HBcrAg levels following a switch from entecavir (ETV) to tenofovir alafenamide (TAF) compared with continued ETV therapy. Methods: This retrospective study included patients with chronic hepatitis B who either switched from ETV to TAF between 2017 and 2022 (ETV–TAF group) or continued ETV therapy during the same period (ETV group). HBcrAg levels were measured annually, and longitudinal changes over 3 years were analyzed based on an index year defined for each patient. Propensity score matching for age, sex, HBcrAg levels, liver transplantation status, and ETV treatment duration yielded 10 patients per group. Results: Baseline characteristics were well balanced after matching. HBV DNA and HBsAg levels remained suppressed in both groups throughout follow-up. The ETV-TAF group showed greater declines in HBcrAg than the ETV group at year 2 (−0.20 vs. −0.10 log U/mL, p = 0.007) and year 3 (−0.30 vs. −0.10 log U/mL, p = 0.006). No virological breakthroughs occurred. Conclusions: Switching from ETV to TAF was associated with greater reductions in HBcrAg levels over 3 years than continued ETV therapy, even in patients with suppressed HBV DNA. These findings suggest that switching to TAF may be associated with further suppression of viral transcriptional activity reflected by HBcrAg reduction and support its potential clinical utility for achieving deeper viral suppression.