Combination Therapy for Chronic HBV Infection

This editorial contextualizes new trial findings on xalnesiran, an siRNA targeting HBV surface antigen administered alone or with immunomodulators (pegylated interferon alfa-2a or ruzotolimod) in patients on nucleos(t)ide analogues. Combination therapy showed greater rates of hepatitis B surface antigen (HBsAg) clearance, with up to 23% achieving off-treatment functional cure. However, relapses occurred post-therapy, raising questions about treatment durability and endpoint timing. The authors emphasize functional cure as the aspirational goal in HBV management, linked to reduced hepatocellular carcinoma risk. The piece explores immunologic mechanisms, drug synergy, and challenges in targeting patients with high HBsAg levels, those at greatest risk but hardest to cure. Future directions include stratified treatment regimens and validated immune restoration models.

This editorial contextualizes new trial findings on xalnesiran, an siRNA targeting HBV surface antigen administered alone or with immunomodulators (pegylated interferon alfa-2a or ruzotolimod) in patients on nucleos(t)ide analogues. Combination therapy showed greater rates of hepatitis B surface antigen (HBsAg) clearance, with up to 23% achieving off-treatment functional cure. However, relapses occurred post-therapy, raising questions about treatment durability and endpoint timing. The authors emphasize functional cure as the aspirational goal in HBV management, linked to reduced hepatocellular carcinoma risk. The piece explores immunologic mechanisms, drug synergy, and challenges in targeting patients with high HBsAg levels, those at greatest risk but hardest to cure. Future directions include stratified treatment regimens and validated immune restoration models.