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

Nancy Reau, MD, of Rush University Medical Center, and Kim Brown, MD, of Henry Ford, welcome Jasmohan Bajaj, MD, MS, of Virginia Commonwealth University and the Richmond VA Medical Center, to discuss the new American College of Gastroenterology (ACG) guideline on hepatic encephalopathy (HE). This first segment of a 3-part series covers what changed in diagnosis, inpatient care, and recurrence prevention.

Liver Lineup: New ACG Hepatic Encephalopathy Guidelines Explained

How Does the New ACG Guideline Change Hepatic Encephalopathy Diagnosis in Clinic?

Bajaj opened by noting patients are older and more comorbid than a decade ago, which complicates what looks like HE. The guideline widens its focus to caregivers, finances, and a new social infrastructure axis, since a patient-only focus misses roughly 50% of the burden, he said.¹

It also adds structured steps for three conditions capable of mimicking or worsening HE. Alcohol use, obstructive sleep apnea, and mild cognitive impairment or dementia each get a defined clinic check. Bajaj noted most sleep disturbance in patients with cardiometabolic disease now traces to sleep apnea, not HE, and he wants to avoid labeling those patients with HE and committing them to lactulose for life. He has described the covert stage as often ignored or confused for overt disease.²

For clinic workflow, Bajaj pointed to the AUDIT-C, which takes about 2 minutes, the STOP-BANG for suspected sleep apnea, and the Mini-Mental State Examination, a rarer positive.

On ammonia, Bajaj was direct. Levels rise in cirrhosis, so a high value in an alert, asymptomatic outpatient does not establish HE, and ammonia alone should neither diagnose nor exclude it.¹ HE remains a clinical diagnosis of exclusion built on patient report and caregiver observations such as near misses, car accidents, and trouble at work.

When other causes are excluded and symptoms persist, the guideline outlines a theragnostic lactulose trial. Bajaj advised starting at a low dose, titrating by the Bristol stool scale to avoid gas and excess stools, and reassessing in person at roughly eight weeks. He estimated about 80% of patients improve and 10% to 15% fail a true trial. For those patients, he suggested neuropsychology referral through primary care, stopping lactulose, and removing the HE diagnosis from the chart because of possible medicolegal consequences.

How Should Hospitalized Patients With Hepatic Encephalopathy Be Managed, and When Should Rifaximin Start?

Brown noted inpatient teams recognize HE more readily because cirrhosis is already known. Bajaj reiterated the guideline's call to look past HE for other causes, including alcohol and stroke. Once HE is suspected, priorities include preventing aspiration pneumonia and hypernatremia, with grade 3 or higher encephalopathy ideally managed in a monitored setting.

Precipitants are also shifting. Bajaj said acute kidney injury and infection now outpace GI bleeding as common triggers. Identifying the trigger is the second step, followed by therapy.

The notable change from prior AASLD and EASL guidance is earlier rifaximin alongside lactulose in the inpatient setting, because patients tolerate it and the combination may work better than lactulose alone.¹ For grade 3 episodes, Bajaj favored lactulose enemas over oral dosing, which risks aspiration.

Because specialists often see patients a day or two after admission, Bajaj urged teaching ED, house, and support staff the basics. These include timely paracentesis to exclude spontaneous bacterial peritonitis, monitored or ICU transfer for grade 3 or higher, and early lactulose. ACG guidelines come with a one-page handout distilling the critical points for posting on units.

How Can Clinicians Prevent Recurrent Hepatic Encephalopathy and Avoid Readmission?

Reau asked what the guideline recommends after the patient clears. Bajaj called recurrence prevention the most important part of HE care and the reason the guideline added social infrastructure as a fifth axis. He estimated 95% of HE admissions could be preventable with 10 to 15 extra minutes spent with the patient, caregiver, family, and pharmacist.

After a first episode, Bajaj recommended a family meeting. He described a recent 35-minute session for a 75-year-old patient and noted the discussion is far harder when the patient is a working breadwinner who drives. Families should learn early warning signs so they do not wait until the patient is comatose, decide whether they are comfortable titrating lactulose, and clarify who checks on a patient living alone.

If the patient has not fully recovered, Bajaj advised at least one CT or MRI, rather than the ultrasound used for HCC surveillance, to look for spontaneous portosystemic shunts. Patients who recur despite adherence and have a relatively low MELD score are candidates for embolization. He added transplant listing deserves consideration at the first episode, given

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 Bausch/Salix, Grifols, Cosmo, and others.

Bajaj JS, Jakab SS, Jesudian AB, et al. ACG clinical guideline: hepatic encephalopathy. 

. 2026;121(3):588-618. doi:10.14309/ajg.0000000000003899

Hillenbrand A. ACG issues new hepatic encephalopathy guidelines for diagnosis, treatment, nutrition, and transplant, with Jasmohan Bajaj, MD, MS. 

. March 24, 2026. Accessed October 9, 2026. 

https://www.hcplive.com/view/acg-issues-new-hepatic-encephalopathy-guidelines-for-diagnosis-treatment-nutrition-and-transplant-with-jasmohan-bajaj-md-ms-

Podcasts

Jasmohan Bajaj, MD, joins Nancy Reau, MD, and Kim Brown, MD, to review what is new in the ACG hepatic encephalopathy guideline.

Liver Lineup: What's New in the ACG Hepatic Encephalopathy Guideline

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

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.

 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.

Nancy Reau, MD

Articles