Nancy Reau, MD, is Professor of Internal Medicine, Richard B. Capps Chair of Hepatology, Associate Director of Solid Organ Transplantation, and Section Chief of Hepatology at Rush University Medical Center.

Nancy Reau, MD

Liver Lineup: Updates & Unfiltered Insights

Liver Lineup: Bepirovirsen and the Push Toward Functional Cure in Hepatitis B

 has gone decades without a finite treatment option, but that may be about to change. On this episode of 

, hosts Nancy Reau, MD, and Kimberly Brown, MD, are joined by Tatyana Kushner, MD, a hepatologist at Weill Cornell Medicine, to discuss bepirovirsen, an investigational antisense oligonucleotide from GSK and Ionis Pharmaceuticals that recently became the first agent to demonstrate functional cure as a phase 3 primary endpoint in chronic hepatitis B (CHB).

Bepirovirsen Phase 3 Data in Chronic Hepatitis B

The conversation centers on data from the B-Well 1 and B-Well 2 trials, presented at the European Association for the Study of the Liver (EASL) Congress and simultaneously published in the New England Journal of Medicine in May 2026. The 2 replicate, double-blind, placebo-controlled trials enrolled 1834 participants across 29 countries with non-cirrhotic CHB who were on stable nucleos(t)ide analogue (NA) therapy and had baseline HBV DNA below 90 IU/mL and HBsAg between 100 and 3000 IU/mL, randomized 2:1 to weekly subcutaneous bepirovirsen 300 mg or placebo alongside standard NA therapy for 24 weeks.

Liver Lineup: HDV Diagnosis, Bulevirtide, and the Delta Pipeline

Liver Lineup: Closing the Gap in Women’s Liver Health

Liver Lineup: Navigating Genetic Testing in Cholestatic Liver Disease

Functional cure at week 72 was achieved in 20% of bepirovirsen-treated patients versus none of the placebo recipients in B-Well 1, and 19% versus 0% in B-Well 2, with response rates climbing further in patients with lower baseline HBsAg — up to 28% among those with baseline HBsAg of 1000 IU/mL or less. Sustained HBV DNA suppression after NA discontinuation, a key secondary endpoint, was reported in 23% of bepirovirsen-treated patients in both studies.

HBsAg Quantification and Patient Selection for Bepirovirsen

Kushner frames HBsAg quantification as the practical starting point for clinicians. She notes that she has begun routinely checking quantitative surface antigen in her own CHB patients, a test she previously considered non-actionable, because it will likely determine eligibility if bepirovirsen is approved. She cites discussion at a Coalition for Hepatitis Elimination conference suggesting roughly 50% to 60% of patients may fall under the HBsAg 3000 IU/mL threshold, though she, Reau, and Brown all note their own clinical experience suggests a lower proportion, complicated by limited access to quantitative, rather than qualitative, assays at some institutions.

Much of the discussion also addresses what functional cure means relative to spontaneous HBsAg loss and continued NA therapy; the group converges on sustained off-treatment HBsAg loss as the accepted endpoint, given its association with reduced HCC and cirrhosis progression risk, while acknowledging open questions about durability beyond the trial window.

Bepirovirsen Dosing, Monitoring, and Safety Considerations

The panel works through practical rollout questions: the drug's weekly injection schedule and potential for at-home administration, and the intensive monitoring likely required in the first 12 weeks given signals for ALT elevation and renal effects. The group agrees cirrhotic and decompensated patients, who were not studied, are unlikely candidates.

Brown highlights a discontinuation rate around 3% in the trials as reassuring relative to older interferon-based regimens, while Kushner cautions that real-world tolerance of ALT flares may differ from the closely monitored trial setting.

What's Next for Bepirovirsen in Hepatitis B Care

The conversation closes on access and uptake — whether primary care practices managing large hepatitis B populations, particularly in Asian American communities, will be positioned to administer and monitor this therapy, or whether care will concentrate in specialized centers. All 3 agree that regardless of uptake, an approval would likely drive renewed attention to hepatitis B screening and treatment linkage, areas where diagnosis and treatment rates in the US remain low.

Bepirovirsen is not yet approved; the FDA has accepted the New Drug Application for priority review and set a PDUFA goal date of October 26, 2026.

Hou J, et al. Phase 3 results of bepirovirsen treatment for chronic hepatitis B virus infection. 

Lok A. A major step toward a cure for hepatitis B infection. 

. 2026;394:2471-2472. doi:10.1056/NEJMe2605575

Brooks A. FDA Grants Bepirovirsen Breakthrough Therapy Designation, Priority Review for Chronic Hepatitis B. HCPLive. April 28, 2026. Accessed July 8, 2026. 

https://www.hcplive.com/view/fda-grants-bepirovirsen-breakthrough-therapy-designation-priority-review-for-chronic-hepatitis-b

Podcasts

Tatyana Kushner, MD, joins Kim Brown, MD, and Nancy Reau, MD, to unpack bepirovirsen's phase 3 data and its implications for HBV care.

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.

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 

 include AbbVie, Gilead, Salix, Arbutus, and VIR. Relevant disclosures for 

 include Mallinckrodt Pharmaceuticals, Gilead, Salix, Intercept, Ipsen, and Madrigal. Relevant disclosures for 

 include Gilead, Abbvie, GSK, Ipsen, Mirum, and Madrigal.

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.

Campbell P. Bulevirtide Receives Historic First FDA Approval for Chronic Hepatitis Delta. HCPLive. May 22, 2026. Accessed June 18, 2026. 

https://www.hcplive.com/view/bulevirtide-historic-first-fda-approval-chronic-hepatitis-delta

Tatyana Kushner, MD, joins hosts Brown and Reau to discuss HDV testing gaps, bulevirtide approval, and the emerging delta hepatitis pipeline.

Are We Screening Women for MASLD Often Enough?

metabolic dysfunction-associated steatotic liver disease (MASLD)

 continues to rise, clinicians are increasingly questioning whether current screening approaches fully capture risk in women. While existing guidelines identify key metabolic risk factors, concerns exist regarding their ability to adequately account for the physiologic changes women experience across the lifespan, particularly during transitions like menopause and pregnancy that significantly influence disease progression.

Current MASLD screening guidelines effectively identify at-risk populations but may not fully account for sex-specific risk across a woman’s lifespan.

The interval of monitoring is important, especially during high-risk transitions such as menopause, when fibrosis progression may accelerate.

Women with metabolic risk factors and early fibrosis may benefit from more frequent noninvasive assessments rather than standard multi-year follow-up.

PCOS screening and recognition should be part of risk assessment in younger women, given its link to insulin resistance and MASLD.

Greater engagement of OB/GYN providers is needed, as they often serve as primary care providers and are well-positioned to identify at-risk patients.

Patient empowerment is essential, including encouraging women to understand their risk, calculate FIB-4 scores, and advocate for further evaluation when steatosis is identified.

, Meena Bansal, MD, joins Nancy Reau, MD, and Kimberly Brown, MD, to examine a critical but often overlooked question in hepatology: should screening strategies for MASLD differ for women?

The discussion begins with Brown raising the possibility that while current guidelines effectively identify at-risk populations like individuals with diabetes, insulin resistance, or metabolic syndrome, they may not fully account for key transitions in a woman’s life. Bansal agrees that existing frameworks are generally sound but emphasizes that timing and frequency of screening are where clinicians may need to adapt their approach.

Rather than redefining who should be screened, Bansal highlights the importance of adjusting monitoring intervals during periods of increased risk, particularly around menopause. As hormonal changes accelerate metabolic dysfunction and fibrosis progression, she suggests that women in this transition, especially those with additional risk factors like diabetes or early fibrosis, may benefit from more frequent noninvasive assessments. Tools such as vibration-controlled transient elastography or serum-based biomarkers can help identify disease progression earlier, creating an opportunity for timely intervention.

Reau reinforces this point with clinical experience, noting that some patients previously considered low risk can return years later with advanced disease, often after significant metabolic changes and menopause, underscoring the need for greater vigilance during these inflection points.

Beyond hepatology, the conversation further expands to the role of multidisciplinary care. Bansal stresses the importance of engaging obstetricians and gynecologists, who often serve as primary care providers for many women. While awareness is growing, she notes that more education is needed to ensure these clinicians incorporate liver disease screening into routine care for at-risk patients. This includes using simple tools like the FIB-4 index as an initial step, followed by additional testing when indicated.

The group also highlights the importance of patient empowerment. Women are frequently told that “fatty liver” is benign, which may delay further evaluation. Encouraging patients to understand their risk factors, calculate their own FIB-4 scores, and advocate for follow-up care can play a meaningful role in earlier detection.

 include Boeheringer-Ingelheim, Boston Pharma, Fibronostics, GSK, Madrigal, Merck, NOVO Nordisk, and The Kinetix Group.

DiStefano JK. NAFLD and NASH in Postmenopausal Women: Implications for Diagnosis and Treatment. Endocrinology. 2020;161(10):bqaa134. doi:10.1210/endocr/bqaa134

Sarkar M, Kushner T. Metabolic dysfunction-associated steatotic liver disease and pregnancy. J Clin Invest. 2025;135(10):e186426. Published 2025 May 15. doi:10.1172/JCI186426

Mass General Brigham. Patients Who Discontinued GLP-1s Had More Weight Gain, Complications During Pregnancy. November 24, 2025. Accessed April 20, 2026. 

https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/pregnancy-effects-from-discontinued-glp-1-use

Videos

Experts call for greater awareness, improved collaboration with OB/GYNs, and more proactive MASLD screening strategies for women.

Screening Smarter: Identifying MASLD Risk in Women

PCOS, Pregnancy, and MASLD Risk: What Clinicians Need to Know

 continues to grow, increasing attention is being paid to how reproductive and metabolic conditions uniquely shape risk in women. Among these, 

 and pregnancy represent critical but often underrecognized periods where hormonal and metabolic factors intersect to influence liver health.

In this segment from a recent episode of 

, Meena Bansal, MD, joins hosts Nancy Reau, MD, and Kimberly Brown, MD, to examine the complex relationship between PCOS, pregnancy, and MASLD.

Bansal emphasizes that PCOS is a well-established risk factor for MASLD and its more advanced form, MASH, largely driven by underlying insulin resistance. While the condition is widely recognized in endocrinology, its implications for liver health are often underappreciated. She notes that patients with PCOS should be evaluated for liver fibrosis using noninvasive tools, and those with evidence of stage 2 or 3 fibrosis may be appropriate candidates for currently approved therapies.

The discussion then shifts to pregnancy as a critical period of risk. Women entering pregnancy with metabolic comorbidities such as obesity or diabetes may already be predisposed to MASLD, and the physiologic changes of pregnancy, including weight gain, can further exacerbate disease progression. According to Bansal, emerging data suggest that MASLD during pregnancy is associated with increased risks of adverse maternal outcomes, including gestational diabetes and preeclampsia, as well as complications for the fetus, such as preterm birth and abnormal growth patterns.

The conversation also touches on the potential for long-term, intergenerational effects. Bansal highlights research suggesting that maternal metabolic health may influence fetal outcomes through epigenetic mechanisms, potentially increasing a child’s lifetime risk of metabolic disease and liver dysfunction. While she says these findings require further validation, they underscore the broader implications of MASLD beyond the individual patient.

Reau and Brown further explore how current therapies fit into this landscape, particularly for younger, premenopausal women. Although GLP-1 receptor agonists have shown benefits in weight loss and metabolic regulation and may even improve menstrual regularity in some patients with PCOS, their use is contraindicated during pregnancy. Bansal points out the challenges this creates in preconception care, including uncertainty around weight regain after discontinuation and its potential impact during pregnancy.

As Bansal notes, more research is needed to better understand how to tailor care for women with MASLD, especially during periods of hormonal and metabolic transition.

Mass General Brigham. Patients Who Discontinued GLP-1s Had More Weight Gain, Complications During Pregnancy. November 24, 2025. Accessed April 17, 2026. 

Experts discuss how metabolic and hormonal factors in women influence MASLD risk, progression, and potential long-term outcomes.

Nancy Reau, MD

Articles