Long-term effectiveness of tenofovir alafenamide versus entecavir in treatment-naïve chronic hepatitis B: A REAL-B study

Background & Aims: While both tenofovir alafenamide (TAF) and entecavir (ETV) are recommended first-line treatments for chronic hepatitis B (CHB), comparative data on their effectiveness remain limited. We aim to compare their virologic (VR), biochemical (BR), and complete (CR) response rates. Methods: This retrospective study enrolled treatment-naïve CHB patients who initiated either TAF or ETV in 2016 or after across 22 international centers and evaluated their treatment response after balancing their characteristics using inverse probability treatment weighting (IPTW) and via Fine-Gray competing-risks analysis of the balanced cohort. Results: The study included 1,605 patients (784 TAF and 821 ETV patients with significant background differences), of whom 1,553 (96.8%) were from Asia. IPTW analysis yielded a total weighted cohort of 1,660 (822 TAF and 838 ETV patients with balanced characteristics). The 5-year cumulative VRs were high in both groups with a slightly higher rate in TAF patients (98.0% vs. 93.9%, P <0.001), and similar findings in a subgroup analysis by median HBV DNA (5.5 log IU/mL). However, there was no significant difference in the 5-year BR rates overall (93.7 vs. 92.8%, P =0.484) or by ALT cutoff of 2× upper limit of normal (ULN). TAF patients had a slightly higher 5-year cumulative CR overall (94.9% vs. 89.4%, P =0.001) and in high HBV DNA (96.9% vs. 87.9%, P <0.001) or ALT ≥2× ULN patients (97.3% vs. 90.6%, P <0.001), but not in those with lower HBV DNA or ALT. Conclusion: BR rates were similar with ETV and TAF, while VR and CR were higher with TAF though the difference was modest (<5% overall, 7-9% in high HBV DNA or ALT groups). Antiviral selection between TAF vs. ETV should be based mainly on cost, side effect profile, and patient preference.