Modeling serum HBsAg, HBV DNA and transaminase kinetics during REP 2139 monotherapy in chronic HBeAg+ HBV infection

Shekhtman, Louis; Borochov, N.; Cotler, Scott J.; Hershkovich, Leeor; Uprichard, Susan L.; Al-Mahtab, M.; Bazinet, Michel; Vaillant, Andrew; Dahari, Harel

doi:10.1016/s0168-8278(18)31264-9

Cited by 2 publications

(1 citation statement)

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“…In particular, we assumed a long HBsAg half-life of 69 days (based on preliminary fitting). Previous work showed high variability in the estimates of the half-life of serum HBsAg, ranging from a few hours up to 38 days Neumann et al (2010);Chulanov et al (2003); Kadelka et al (2021); Shekhtman et al (2018);Hershkovich et al (2023); Shekhtman et al (2020). Future work is needed to determine whether the longer half-life is a characteristic of our animal model.…”

Section: Discussionmentioning

confidence: 98%

Mathematical Models of Early Hepatitis B Virus Dynamics in Humanized Mice

Ciupe,

Dahari,

Ploss

2024

Bull Math Biol

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Analyzing the impact of the adaptive immune response during acute hepatitis B virus (HBV) infection is essential for understanding disease progression and control. Here we developed mathematical models of HBV infection which either lack terms for adaptive immune responses, or assume adaptive immune responses in the form of cytolytic immune killing, non-cytolytic immune cure, or non-cytolytic-mediated block of viral production. We validated the model that does not include immune responses against temporal serum hepatitis B DNA (sHBV) and temporal serum hepatitis B surface-antigen (HBsAg) experimental data from mice engrafted with human hepatocytes (HEP). Moreover, we validated the immune models against sHBV and HBsAg experimental data from mice engrafted with HEP and human immune system (HEP/HIS). As expected, the model that does not include adaptive immune responses matches the observed high sHBV and HBsAg concentrations in all HEP mice. By contrast, while all immune response models predict reduction in sHBV and HBsAg concentrations in HEP/HIS mice, the Akaike Information Criterion cannot discriminate between non-cytolytic cure (resulting in a class of cells refractory to reinfection) and antiviral block functions (of up to $$99\%$$ 99 % viral production 1–3 weeks following peak viral load). We can, however, reject cytolytic killing, as it can only match the sHBV and HBsAg data when we predict unrealistic levels of hepatocyte loss.

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Section: Discussionmentioning

confidence: 98%