Kenda Al-Assi, MD, Dana Al-Assi, MD, Cheryl Levine, PhD, NP, Zaid Al-Assi, MD, Reem Ghalib, MD, MS Texas Clinical Research Institute, Arlington, TX Introduction: Chronic hepatitis B (HBV) infection can remain quiescent under long-term antiviral therapy. HBV reactivation can be caused by known factors including immunosuppression, antiviral resistance or medication non-compliance. GLP-1 receptor agonists (e.g. semaglutide) are widely used for diabetes and obesity and have a generally favorable hepatic safety profile. General drug/drug interaction data suggest that antivirals and semaglutide can be combined safely.
Case Description/
Methods: A 60-year-old Vietnamese male with a history of chronic HBV managed with entecavir presented with biochemical hepatitis following initiation of weekly semaglutide for diabetes management. He had been compliant with 0.5 mg entecavir daily for 8 years, which was increased to 1 mg two years prior due to a detectable low-level viral load.
At baseline HBV DNA was 337 IU/mL, with normal liver enzymes. After starting semaglutide, asymptomatic lab monitoring revealed AST 112 U/L, ALT 235 U/L. His HBV DNA increased to 194,000 IU/mL and later to 7,620,000 IU/ml despite continued compliance with entecavir.
Serologic and genetic testing showed no evidence of co-infection with hepatitis delta, A, C, or E, EBV, CMV and no mutations predicting entecavir resistance. The patient was switched to tenofovir alafenamide. Subsequent viral load dropped gradually to < 10 IU/mL and the liver enzymes normalized. Discussion: This case highlights an unexpected temporal association between semaglutide initiation and HBV reactivation with hepatocellular injury. As no antiviral resistance or other causes were identified, it suggests an alternative mechanism.
Semaglutide is not known to be directly hepatotoxic; however, its delayed gastric emptying may reduce the absorption of orally administered medications such as entecavir, which requires an empty stomach for optimal bioavailability. Subtherapeutic drug levels could lead to impaired viral suppression even in the absence of resistance mutations.
This mechanism is plausible given the concurrent elevation in HBV DNA and liver enzymes without antiviral resistance, followed by a virologic response after switching to tenofovir alafenamide, a drug with more consistent absorption regardless of food.
Strategies to manage patients on chronic anti-viral therapy being prescribed GLP-1 agonist should include close monitoring of HBV DNA and liver enzymes in addition to possibly considering different dosing regimen for semaglutide and the impact of food on medication absorption.
Disclosures: Kenda Al-Assi indicated no relevant financial relationships. Dana Al-Assi indicated no relevant financial relationships. Cheryl Levine: Abbvie – Sub-Investigator. Abivax – Sub-Investigator. ATEA – Sub-Investigator. Boehringer Engelheim – Sub-Investigator. c – Sub-Investigator. Galectin – Sub-Investigator. Gilead – Sub-Investigator. Hanmi – Sub-Investigator. Inventiva – Sub-Investigator. Ipsen – Sub-Investigator. Madrigal – Sub-Investigator. Merck – Sub-Investigator. Novo Nordisk – Sub-Investigator. Roche – Sub-Investigator. Sagimet – Sub-Investigator. Zydus – Sub-Investigator. Zaid Al-Assi indicated no relevant financial relationships. Reem Ghalib: Abbvie – Principal Investigator. Abivax – Sub-Investigator. ATEA – Principal Investigator. Boehringer Engelheim – Principal Investigator. Corcept – Principal Investigator. Galectin – Principal Investigator. Gilead – Principal Investigator. Hanmi – Principal Investigator. Inventiva – Principal Investigator. Ipsen – Principal Investigator. Madrigal – Principal Investigator. Merck – Principal Investigator. Novo Nordisk – Principal Investigator. Roche – Principal Investigator. Sagimet – Principal Investigator. Zydus – Principal Investigator.
Kenda Al-Assi, MD, Dana Al-Assi, MD, Cheryl Levine, PhD, NP, Zaid Al-Assi, MD, Reem Ghalib, MD, MS. P6123 - Hepatitis B Reactivation in a Patient on Long-Term Entecavir Following Initiation of Semaglutide: A Case Report, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
