In this episode of Liver Lineup: Updates and Unfiltered Insights, hosts Kimberly Brown, MD, and Nancy Reau, MD, are joined by Tatyana Kushner, MD, a hepatologist at Weill Cornell Medicine, for a wide-ranging discussion on hepatitis delta virus (HDV), from longstanding barriers to diagnosis to the first US-approved treatment and what comes next in the pipeline.
Key Episode Timestamps
0:01:30 – Introduction, framing of New York/Chicago as HDV “hotspots” driven by immigrant populations and under-recognized disease burden.
0:05:18 – Historical under-testing for HDV in HBV patients and VA data showing <10% of HBV patients ever receive delta testing despite higher rates of cirrhosis and HCC.
0:07:55 – Discussion of evolving guidelines and anticipation that AASLD will move toward testing all HBsAg-positive individuals at least once for HDV.
0:10:49 – Practical care cascade overview: who to test, HDV antibody followed by HDV RNA, and how to interpret discordant or low-level results.
0:20:13 – Historical treatment approach with pegylated interferon, trial access, and the unmet need in patients excluded from studies or with advanced disease.
0:26:16 – Debate on combining pegylated interferon with bulevirtide versus long-term bulevirtide monotherapy, including tolerability and “finite” versus maintenance strategies.
0:35:11 – Forward-looking segment on bulevirtide approval in the US, its practical use (daily injection, reconstitution), and pipeline agents with promising data.
Kushner opens by reflecting on how dramatically the field's attention to HDV has shifted. For much of her early career, delta hepatitis was treated as an afterthought at national conferences, with little urgency around testing or treatment. Over the past 5 years, growing evidence on rapid disease progression, elevated risk of cirrhosis and hepatocellular carcinoma, and now an approved therapeutic have changed the calculus entirely.
A central theme of the conversation is the persistent gap between how many patients likely have HDV and how many have ever been tested for it. Kushner describes early research she conducted with colleagues in the national VA system showing fewer than 10% of hepatitis B surface antigen-positive patients had ever received a delta test despite measurably more advanced liver disease among those ultimately found to be co-infected. Reau and Brown echo this, noting guidelines have historically tied testing to specific risk factors or abnormal transaminases, a standard both hosts view as too narrow given HDV's clinical consequences.
All 3 clinicians express support for universal testing in all hepatitis B surface antigen-positive individuals. Reau notes AASLD is expected to release updated hepatitis D guidance, and signals her expectation the society will move toward recommending at-least-once screening in all HBsAg-positive patients. The discussion also covers the practical mechanics of the diagnostic cascade, from HDV antibody to reflex HDV RNA, and the logistical hurdles, from send-out testing delays to billing complexities, institutions have faced in trying to implement reflex testing programs.
The episode also serves as an on-the-ground assessment of bulevirtide (Hepcludex), approved by the US Food and Drug Administration in May 2026 for chronic HDV infection. Kushner walks through the administration requirements, including daily self-injection with patient-performed reconstitution, and notes Gilead's decision to formulate the US 8.5 mg dose without refrigeration requirements, a deliberate improvement over the European 2 mg formulation.
She and Reau discuss the practical question of whether to combine bulevirtide with pegylated interferon in appropriate candidates, particularly those with less advanced fibrosis who may be candidates for finite therapy. Recent data showed meaningfully higher off-treatment response rates at the 10 mg dose compared to the 2 mg combination arm, a point that generated notable discussion at the recent EASL conference and the Hepatitis Delta International Network meeting.
Reau draws on her experience running clinical trials including the lonafarnib program, and both she and Brown emphasize the institutional muscle memory built from treating hepatitis C with interferon-based regimens — expertise she argues will be directly relevant as clinicians reintroduce pegylated interferon for select delta patients.
Kushner closes with an overview of the pipeline beyond bulevirtide, highlighting a pair of phase 3 programs: Vir Biotechnology’s study evaluating tobevibart plus elebsiran, a combination of a monoclonal antibody and siRNA, and a study of brilovertug from Bluejay Therapeutics, recently acquired by Mirum Pharmaceuticals. Both have demonstrated higher rates of undetectable HDV RNA in phase 2 results than bulevirtide in comparable timeframes, and both have closed screening. Head-to-head trials against bulevirtide are planned for both programs.
Editors’ note: Relevant disclosures for Reau include AbbVie, Gilead, Salix, Arbutus, and VIR. Relevant disclosures for Brown include Mallinckrodt Pharmaceuticals, Gilead, Salix, Intercept, Ipsen, and Madrigal. Relevant disclosures for Kushner include Gilead, Abbvie, GSK, Ipsen, Mirum, and Madrigal.
References
US Centers for Disease Control and Prevention. Hepatitis D Basics. April 24, 2024. Accessed June 18, 2026. https://www.cdc.gov/hepatitis-d/about/index.html
Lange M, Zaret D, Kushner T. Hepatitis Delta: Current Knowledge and Future Directions. Gastroenterol Hepatol (N Y). 2022;18(9):508-520.
