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Review
. 2022 Mar 22;14(4):657.
doi: 10.3390/v14040657.

HBsAg Loss as a Treatment Endpoint for Chronic HBV Infection: HBV Cure

Maryam Moini  1 , Scott Fung  2
Affiliations
Review

HBsAg Loss as a Treatment Endpoint for Chronic HBV Infection: HBV Cure

Maryam Moini et al. Viruses. .

Abstract

Despite the availability of effective vaccines and antiviral therapy over the past two to three decades, chronic hepatitis B virus (HBV) infection remains a major global health threat as a leading cause of cirrhosis and liver cancer. Functional HBV cure defined as hepatitis B surface antigen (HBsAg) loss and undetectable serum HBV DNA is associated with improved clinical outcomes in patients with chronic HBV infection. However, spontaneous loss of HBsAg is rare and occurs in only 1% of all HBsAg-positive individuals annually. Furthermore, the rate of functional cure with currently available antiviral therapy is even lower, <1% patients on treatment per year. Nonetheless, HBsAg loss has become the new target or therapeutic endpoint for antiviral treatment. Recently, there has been much excitement surrounding the development of novel antiviral agents such as small interfering RNA (siRNA), core assembly modulators (CAMs), nucleic acid polymers (NAPs) among others, which may be used in combination with nucleos(t)ide analogs and possibly immunomodulatory therapies to achieve functional cure in a significant proportion of patients with chronic hepatitis B. Novel assays with improved sensitivity for detection of very low levels of HBsAg and to determine the source of HBsAg production will also be required to measure efficacy of newer antiviral treatments for HBV cure. In this narrative review, we will define HBV cure, discuss various sources of HBsAg production, evaluate rates of HBsAg loss with current and future antiviral agents, review clinical factors associated with spontaneous HBsAg loss, and explore clinical implications of functional cure.

Keywords: HBV cure; antiviral therapy; hepatitis B surface antigen (HBsAg); hepatitis B virus (HBV).

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Conflict of interest statement

S.F. serves as an advisor for Gilead Sciences, Janssen, Abbvie, Assembly Biosciences, Pfizer and Novo-Nordisk; receives research support from Gilead Sciences; speaks and teaches for Gilead Sciences, Abbvie and Lupin. M.M. declares no conflict of interest.

Figures

Figure 1
Figure 1
Different Sources of Hepatitis B s antigen (HBsAg) in the body. Red crosses show various pathways that are inhibited by different antiviral medications.
Figure 2
Figure 2
Different patterns of decline in quantitative HBsAg levels in patients with chronic hepatitis B on antiviral treatment and management plan for each pattern. * In HBe antigen negative, non-cirrhotic patients.
See this image and copyright information in PMC

Comment in

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