The article "Toward a Functional Cure for Hepatitis B" by Anna S. F. Lok discusses the current challenges and progress in achieving a functional cure for chronic hepatitis B virus (HBV) infection. While pegylated interferon-α (pegIFN-α) and nucleos(t)ide analogues (NAs) can suppress HBV replication and reduce liver inflammation, they rarely lead to the loss of hepatitis B surface antigen (HBsAg). A functional cure is defined as undetectable HBsAg and unquantifiable serum HBV DNA for at least 24 weeks after therapy. Direct-acting antivirals (DAAs) targeting various stages of the HBV lifecycle, such as entry, capsid assembly, and protein production, are being tested in clinical trials. Immune modulatory therapies aimed at restoring HBV-specific immune responses are also under investigation. Recent combinations of DAAs and immune modulatory therapies, particularly those including pegIFN-α, have shown promising results. However, these findings need to be confirmed in larger studies with longer follow-up. The article highlights the importance of developing therapies that are safe, effective, and provide incremental value compared to current standard treatments, which are predominantly long-term NA therapy. The challenges include the presence of covalently closed circular DNA (cccDNA) and integrated HBV DNA, as well as the need to restore HBV-specific immune responses. The article concludes by emphasizing the progress made and the need for further research to achieve a functional cure for HBV.The article "Toward a Functional Cure for Hepatitis B" by Anna S. F. Lok discusses the current challenges and progress in achieving a functional cure for chronic hepatitis B virus (HBV) infection. While pegylated interferon-α (pegIFN-α) and nucleos(t)ide analogues (NAs) can suppress HBV replication and reduce liver inflammation, they rarely lead to the loss of hepatitis B surface antigen (HBsAg). A functional cure is defined as undetectable HBsAg and unquantifiable serum HBV DNA for at least 24 weeks after therapy. Direct-acting antivirals (DAAs) targeting various stages of the HBV lifecycle, such as entry, capsid assembly, and protein production, are being tested in clinical trials. Immune modulatory therapies aimed at restoring HBV-specific immune responses are also under investigation. Recent combinations of DAAs and immune modulatory therapies, particularly those including pegIFN-α, have shown promising results. However, these findings need to be confirmed in larger studies with longer follow-up. The article highlights the importance of developing therapies that are safe, effective, and provide incremental value compared to current standard treatments, which are predominantly long-term NA therapy. The challenges include the presence of covalently closed circular DNA (cccDNA) and integrated HBV DNA, as well as the need to restore HBV-specific immune responses. The article concludes by emphasizing the progress made and the need for further research to achieve a functional cure for HBV.