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Rapid monophasic HBsAg decline during nucleic-acid polymer-based therapy predicts functional cure
Leeor Hershkovich1, Louis Shekhtman1,2, Michel Bazinet3
1Program for Experimental & Theoretical Modeling, Department of Medicine, Division of Hepatology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
Hepatology Communications
|July 17, 2023
Summary
Functional cure in chronic hepatitis B is linked to a rapid, single-phase decline in Hepatitis B surface antigen (HBsAg) during nucleic-acid polymer (NAP)-based therapy. A non-monophasic HBsAg pattern predicts a lack of functional cure.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Chronic hepatitis B (CHB) requires effective therapies to achieve functional cure, defined by undetectable Hepatitis B surface antigen (HBsAg) and HBV DNA.
- Nucleic-acid polymer (NAP)-based therapies offer a potential strategy for CHB management, but understanding kinetic patterns associated with cure is crucial.
- Interplay of serum HBV DNA, HBsAg, anti-HBs, and ALT provides insights into treatment response during CHB therapy.
Purpose of the Study:
- To analyze the kinetic patterns of HBsAg, HBV DNA, and ALT during NAP-based therapy in patients with HBeAg-negative CHB.
- To identify specific kinetic profiles associated with achieving a functional cure after treatment cessation.
- To evaluate the predictive value of HBsAg kinetics for functional cure.
Main Methods:
- The REP 401 study enrolled HBeAg-negative CHB patients receiving initial tenofovir-disoproxil-fumarate (TDF) monotherapy, followed by triple therapy (TDF + pegylated interferon-α2a + NAPs).
- Participants were categorized into early or delayed triple therapy groups.
- Functional cure was assessed 48 weeks post-treatment; kinetic patterns (monophasic vs. biphasic decline) were defined by slope changes in HBsAg levels.
Main Results:
- Thirty-seven participants completed the study; 35% achieved functional cure.
- All participants maintained undetectable HBV DNA throughout TDF monotherapy and combination therapies.
- A monophasic HBsAg decline during triple therapy was observed in all participants who achieved functional cure, with a significantly shorter time to HBsAg loss compared to non-responders.
Conclusions:
- Functional cure of CHB is strongly associated with a rapid, monophasic HBsAg decline during NAP-based triple therapy.
- A non-monophasic HBsAg kinetic pattern demonstrates a 100% negative predictive value for functional cure.
- Monitoring HBsAg kinetics provides valuable prognostic information for predicting treatment outcomes in CHB.
