Modelling hepatitis D virus RNA and HBsAg dynamics during nucleic acid polymer monotherapy suggest rapid turnover of HBsAg.

Autor: Shekhtman L; The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA.; Network Science Institute, Northeastern University, Boston, MA, USA., Cotler SJ; The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA., Hershkovich L; The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA., Uprichard SL; The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA., Bazinet M; Replicor Inc., 6100 Royalmount Avenue, Montreal, Quebec, H4P 2R2, Canada., Pantea V; Department of Infectious Diseases, Nicolae, Testemiţanu State University of Medicine and Pharmacy, Chișinău, Moldova., Cebotarescu V; Department of Infectious Diseases, Nicolae, Testemiţanu State University of Medicine and Pharmacy, Chișinău, Moldova., Cojuhari L; Department of Infectious Diseases, Nicolae, Testemiţanu State University of Medicine and Pharmacy, Chișinău, Moldova., Jimbei P; Toma Ciorbă Infectious Clinical Hospital, Chișinău, Moldova., Krawczyk A; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Dittmer U; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Vaillant A; Replicor Inc., 6100 Royalmount Avenue, Montreal, Quebec, H4P 2R2, Canada. availlant@replicor.com., Dahari H; The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA. hdahari@luc.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 May 12; Vol. 10 (1), pp. 7837. Date of Electronic Publication: 2020 May 12.
DOI: 10.1038/s41598-020-64122-0
Abstrakt: Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) for its assembly and release. Current HBV treatments are only marginally effective against HDV because they fail to inhibit HBsAg production/secretion. However, monotherapy with the nucleic acid polymer REP 2139-Ca is accompanied by rapid declines in both HBsAg and HDV RNA. We used mathematical modeling to estimate HDV-HBsAg-host parameters and to elucidate the mode of action and efficacy of REP 2139-Ca against HDV in 12 treatment-naive HBV/HDV co-infected patients. The model accurately reproduced the observed decline of HBsAg and HDV, which was simultaneous. Median serum HBsAg half-life (t 1/2 ) was estimated as 1.3 [0.9-1.8] days corresponding to a pretreatment production and clearance of ~10 8 [10 7.7 -10 8.3 ] IU/day. The HDV-infected cell loss was estimated to be 0.052 [0.035-0.074] days -1 corresponding to an infected cell t 1/2  = 13.3 days. The efficacy of blocking HBsAg and HDV production were 98.2 [94.5-99.9]% and 99.7 [96.0-99.8]%, respectively. In conclusion, both HBsAg production and HDV replication are effectively inhibited by REP 2139-Ca. Modeling HBsAg kinetics during REP 2139-Ca monotherapy indicates a short HBsAg half-life (1.3 days) suggesting a rapid turnover of HBsAg in HBV/HDV co-infection.
Databáze: MEDLINE
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