Integrated DNA Drives Surface Antigen Production in HBeAg-Negative Hepatitis B

Chronic hepatitis B remains a significant global health burden, with the persistence of the hepatitis B e antigen (HBeAg) serving as a key marker for disease progression and the necessity of antiviral intervention [1, 2]. While the loss of HBeAg represents a degree of immune control, clinicians often face challenges in managing patients who remain positive for the hepatitis B surface antigen (HBsAg) despite low viral replication [1, 3]. Current clinical guidelines emphasize the importance of monitoring viral DNA and surface antigen levels to assess the risk of cirrhosis and hepatocellular carcinoma [3, 4]. However, the underlying intrahepatic mechanisms that drive HBsAg production in different clinical phases of the infection are not fully understood, complicating the pursuit of a functional cure [2, 5]. A recent study examines the distinct patterns of intrahepatic viral DNA to clarify these differences across the natural history of the disease, offering insights into why surface antigen clearance remains so difficult to achieve in practice.