Current evidence of bulevirtide as monotherapy compared to combination treatment with pegylated interferon for...

Pegylated interferon alpha-2a (PEG-IFN) has been used off-label as chronic hepatitis delta (CHD) treatment since the 1990s. However, it has not received formal approval for this indication. Bulevirtide (BLV), a first-in-class entry inhibitor, is the first drug approved for the treatment of compensated CHD. Since its conditional approval in 2020, data from clinical trials and real-world studies have emerged. Literature search included PubMed (last accessed July 2025), European Medicines Agency official reports, and international conference abstract books.

Several evidence gaps remain unmet, including the definition of treatment endpoints, the impact of therapy on clinical outcomes, optimal therapy duration, and the potential benefits of combination with PEG-IFN. This review aims to provide a comprehensive overview of the current evidence regarding the use of BLV, both as monotherapy and in combination with PEG-IFN.

Bulevirtide 2 mg is an effective treatment for CHD in patients with and without advanced chronic liver disease, as demonstrated in clinical trials and real-world cohorts. In addition, long-term therapy appears to enhance response rates and may even promote the loss of HDV-infected hepatocytes, potentially leading to a sustained off-therapy response. However, new therapeutic strategies are needed for patients who do not respond.