Pegylated interferon for chronic hepatitis delta: does it still have a role in the bulevirtide era?

Chronic hepatitis delta is the most aggressive form of chronic viral hepatitis. Although pegylated interferon alfa (PegIFNα) has been the reference treatment for decades, the recent introduction of bulevirtide raises questions about its current role. To evaluate our real-world experience with PegIFNα, we conducted an observational, retrospective, single-centre study including patients with chronic hepatitis delta virus infection followed between 2014 and 2026. Fifteen patients were included, of whom 8 received PegIFNα. Toxicity was common, mainly due to haematological adverse effects, although flu-like symptoms and one serious neuropsychiatric event were also recorded. Of seven patients who completed treatment, two achieved a sustained virological response. Both patients also achieved HBV functional cure, being the only patients in the cohort to reach this endpoint. Our results confirm the considerable toxicity and limited efficacy of PegIFNα, but also its capacity to induce a sustained virological response and HBV functional cure in a subgroup of patients. In the bulevirtide era, PegIFNα remains a valid treatment option in selected patients given its curative potential.