Hepatitis B Surface Antigen Loss: What Does Integration Have to Do With a Functional Hepatitis B Virus Cure?

Worldwide, approximately, 400 million people have a chronic hepatitis B virus (HBV) infection (CHB), which is a leading cause of liver-related death.(1)A highly effective vaccine has prevented millions of infections, but belies the challenge to treat and cure those with CHB.The complexity of current HBV treatment guidelines is partially attributed to the sub-optimal, oral antiviral treatments for CHB that are available: nucleos(t)ide analogues (NUCs) only suppress viral replication but do not eliminate viral genomes from hepatocytes in the liver where they reside.Treatment is reserved only for persons with signs of liver damage especially when there is abundant viral replication.Furthermore, when treatment is initiated, it is lifelong for the majority of people.Therefore, better medicines are needed for CHB.Management of CHB requires monitoring the blood for hepatitis B surface antigen (HBsAg).People who develop the lowest levels of HBsAg (historically called "HBsAg loss") are considered functionally cured.Because a small proportion of people treated with NUCs achieve HBsAg loss after NUC discontinuation, there is hope for this type of cure.Functional cure is most similar to spontaneous HBV recovery in that HBsAg is not detectable in blood but some hepatocytes retain HBV viral genomes.(2, 3) People who achieve HBsAg loss are considered only functionally cured because these genomes can reactivate during immunosuppression.