2025 was a consequential year across the hepatitis landscape, marked by notable therapeutic advances, evolving clinical guidance, and policy decisions with far-reaching implications for patient care. Progress spanned viral hepatitis subtypes, reflecting both scientific momentum and ongoing debates around prevention, long-term safety, and global access to effective therapies.

Innovation was especially evident in hepatitis B, C, and delta treatment. Brelovitug’s Breakthrough Therapy designation from the US Food and Drug Administration (FDA) signaled rare momentum in chronic hepatitis D, while multiple HBV developments, from antifibrotic data with hydronidone to improved renal and bone outcomes with besifovir, highlighted a shift toward safer, more comprehensive long-term management. In hepatitis C, the FDA’s label expansion of glecaprevir/pibrentasvir for acute infection represented a major step forward in early intervention and cure.

At the same time, 2025 underscored the importance of guidance and policy in shaping hepatitis care. Updated American Gastroenterological Association (AGA) recommendations refined strategies for preventing HBV reactivation in at-risk patients, while a controversial US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) decision on infant hepatitis B vaccination sparked widespread clinical concern and renewed discussion around public health priorities.

FDA News

Brelovitug Receives FDA Breakthrough Therapy Designation for Chronic Hepatitis Delta

On January 21, 2025, the FDA granted Breakthrough Therapy designation to Bluejay Therapeutics’ brelovitug (BJT-778) for the treatment of chronic hepatitis delta. The decision cae just 2 months after phase 2 data demonstrating 100% virologic response and up to 78% combined virologic response and alanine aminotransferase (ALT) normalization with brelovitug monotherapy were presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2024.

FDA Approves Glecaprevir/Pibrentasvir (Mavyret) Label Expansion for Acute HCV

On June 11, 2025, the FDA approved a label expansion for AbbVie’s glecaprevir/pibrentasvir (Mavyret), an oral pangenotypic direct acting antiviral (DAA) therapy. With this decision, glecaprevir/pibrentasvir is now approved for the treatment of adults and pediatric patients ≥ 3 years of age with acute or chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis.

The approval was supported by data from the phase 3, multicenter, single-arm prospective M20-350 study evaluating the safety and efficacy of glecaprevir/pibrentasvir 8-week treatment in adults with acute HCV infection. Of note, the decision made glecaprevir/pibrentasvir the first and only DAA therapy approved to treat patients with acute HCV in 8 weeks with a 96% cure rate.

Trial Updates and New Guidelines

AGA Releases Clinical Practice Update on HBV Reactivation Prevention, Treatment

Later in January, the AGA released a clinical practice guideline update on the prevention and treatment of hepatitis B virus (HBV) reactivation in at-risk individuals. The new guideline addresses research published since the first iteration was released in 2014 and provides 4 key clinical recommendations regarding the role of antiviral prophylaxis and monitoring without antiviral prophylaxis for management of HBV reactivation based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations.

Besifovir Improves Renal, Bone Health in HBV Patients Receiving Long-Term TDF

Data from a randomized, open-label, active-controlled, non-inferiority phase 4 clinical trial suggest switching to besifovir dipivoxil maleate (BSV) therapy may improve renal and bone health in patients with HBV previously receiving long-term tenofovir disoproxil fumarate (TDF) treatment. Results showed switching to a 48-week BSV therapy regimen after long-term TDF demonstrated noninferior antiviral efficacy compared to maintaining TDF. Additionally, findings suggest certain adverse effects of long-term TDF may be reversible with BSV, which was linked to improved kidney function and bone density.

Hydronidone Meets Primary Endpoint in Phase 3 Hepatitis B Trial

Gyre Therapeutics’ hydronidone met the primary endpoint for ≥1-stage regression in liver fibrosis compared to placebo in a pivotal phase 3 trial evaluating its efficacy and safety for the treatment of liver fibrosis in patients with chronic hepatitis B in China. Based on these data, the Company described plans to file a New Drug Application with China’s NMPA and preparations to file an investigational new drug (IND) application.

CDC Changes Infant Hepatitis B Vaccine Recommendation

On December 5, 2025, the CDC ACIP voted 8 to 3 to recommend individual-based decision-making for parents deciding whether to give the hepatitis B vaccine, including the birth dose, to infants born to women who test negative for the virus.

For infants not receiving the birth dose, ACIP suggested in its recommendation that the initial dose be administered no earlier than 2 months of age. ACIP additionally voted to recommend that when evaluating the need for a subsequent hepatitis B vaccine dose in children, parents should consult with health care providers to decide whether to test antibody levels to hepatitis surface antigen to evaluate adequacy of protection through serology results.

Related: Clinical Concerns Over the ACIP Infant Hepatitis B Vaccine Decision, With Chari Cohen, DrPH, MPH

Podcasts

Liver Lineup: Navigating Hepatitis B Prevention After ACIP’s Birth Dose Shift

In this episode of Liver Lineup: Updates and Unfiltered Insights, hosts Nancy Reau, MD, and Kimberly Brown, MD, discuss the implications of the CDC ACIP vote to remove the universal birth-dose hepatitis B vaccine recommendation for infants born to mothers who test negative for HBV.

Liver Lineup: Progress, Policy, and Barriers in Hepatitis C Elimination

In this episode, hosts discuss the progress and persistent challenges in eliminating hepatitis C, exploring the major policy, clinical, and structural milestones enabling this effort as well as the critical gaps in diagnosis, treatment access, and health policy that still impede progress.

References

1. Brooks A. Brelovitug Receives FDA Breakthrough Therapy Designation for Chronic Hepatitis Delta. HCPLive. January 21, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/brelovitug-receives-fda-breakthrough-therapy-designation-chronic-hepatitis-delta

2. Brooks A. AGA Releases Clinical Practice Update on HBV Reactivation Prevention, Treatment. HCPLive. January 24, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/aga-releases-clinical-practice-update-hbv-reactivation-prevention-treatment

3. Brooks A. Besifovir Improves Renal, Bone Health in HBV Patients Receiving Long-Term TDF. HCPLive. April 12, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/besifovir-improves-renal-bone-health-hbv-patients-receiving-long-term-tdf

4. Brooks A. Hydronidone Meets Primary Endpoint in Phase 3 Hepatitis B Trial. HCPLive. May 22, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/hydronidone-meets-primary-endpoint-phase-3-hepatitis-b-trial

5. Brooks A. FDA Approves Glecaprevir/Pibrentasvir (Mavyret) Label Expansion for Acute HCV. HCPLive. June 12, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/fda-approves-glecaprevir-pibrentasvir-mavyret-label-expansion-for-acute-hcv

6. Brooks A. CDC Changes Infant Hepatitis B Vaccine Recommendation. HCPLive. December 5, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/cdc-changes-infant-hepatitis-b-vaccine-recommendation

7. Reau N, Brown KA. Liver Lineup: Navigating Hepatitis B Prevention After ACIP’s Birth Dose Shift. HCPLive. December 10, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/liver-lineup-navigating-hepatitis-b-prevention-after-acip-birth-dose-shift

8. Reau N, Brown KA. Liver Lineup: Progress, Policy, and Barriers in Hepatitis C Elimination. HCPLive. July 14, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/liver-lineup-progress-policy-barriers-hepatitis-c-elimination