New Paradigms in Hepatitis D: Screening, Treatment, and the Path to Cure

Abstract

Abstract Chronic hepatitis D virus infection, also known as chronic hepatitis delta, remains the most severe form of chronic viral hepatitis, associated with accelerated liver disease progression, cirrhosis, decompensation, and hepatocellular carcinoma. Recent years have seen major advances in screening strategies and antiviral therapies for hepatitis D. This review discusses evidence supporting broader hepatitis D screening among hepatitis B surface antigen (HBsAg)-positive individuals and practical considerations for implementation across epidemiological settings, and reviews current and emerging treatments—entry inhibition (bulevirtide), prenylation inhibition (lonafarnib), immune-modulatory therapies (pegylated interferons), and HBsAg-targeting approaches (tobevibart, elebsiran, brelovitug, and nucleic acid polymers)—focusing on treatment response and durability of viral suppression. In conclusion, emerging therapies have substantially improved antiviral efficacy, shifting the focus of hepatitis D management from on-treatment suppression toward durable off-treatment control and functional cure, changing the diagnosis, treatment, and long-term management of chronic hepatitis D.