HBsAg Negative Does Not Always Mean HBV Negative: Nature Reviews Gastroenterology & Hepatology | September 2026
What Does the Review Clarify?
This major review provides a practical framework for understanding and investigating occult hepatitis B virus infection (OBI).
OBI means replication-competent HBV DNA despite negative HBsAg.
Anti-HBc positivity indicates previous HBV exposure but does not itself diagnose OBI.
OBI should be actively considered in cryptogenic cirrhosis and hepatocellular carcinoma.
When OBI is confirmed in these settings, nucleos(t)ide analogue therapy should be considered.
Routine OBI screening is not supported for otherwise mild chronic liver disease.
HBsAg-negative, anti-HBc-positive patients receiving chemotherapy, biologics, potent immunosuppression or transplantation require careful HBV-reactivation risk assessment.
Why Does It Matter?
HBV can persist despite apparent serological resolution and may become clinically important during profound immunosuppression.
GastroAGI Takeaway
Do not equate negative HBsAg with complete viral eradication—but do not search for OBI indiscriminately either. HBV-DNA testing should be targeted to clinically meaningful settings, particularly unexplained advanced liver disease and patients at significant risk of HBV reactivation.
