EASL 2025 indications revisited: phase-specific outcomes with and without nucleos(t)ide analogue therapy in chronic hepatitis B virus infection.

Nucleos(t)ide analogues therapy significantly reduces risks of cirrhosis and hepatocellular carcinoma in specific chronic hepatitis B subgroups outside 2025 EASL criteria, especially in HBeAg-positive patients with high replicative or impending phase transition phenotypes.

• Why it matters: Understanding the long-term benefits of NAs therapy beyond current treatment guidelines is crucial for optimizing management of chronic HBV infection and preventing severe liver outcomes in diverse patient groups.
• What they did: We analyzed data from 30,784 Chinese chronic HBV individuals outside 2025 EASL treatment criteria, categorizing them into four groups based on HBeAg status, age, HBV DNA levels, and fibrosis, and assessed the association between NAs therapy and the incidence of cirrhosis and HCC over 5 years.
• The result: NAs therapy was linked to a substantial reduction in cirrhosis and HCC risks in Group 1 (HR 0.18 and 0.03) and Group 2 (HR 0.50 and 0.25), supporting expanded treatment indications for these phenotypes, while no significant effects were observed in Groups 3 and 4.