In the last decade hepatitis C virus (HCV) kinetics has become an important clinical tool for the optimization of therapy with (pegylated)-interferon-α (IFN) and ribavirin (RBV). Mathematical models have generated important insights into HCV pathogenesis, HCV- host dynamics, and IFN and RBV's modes of action. Clinical trials with direct acting agents (DAAs) against various steps of the HCV life cycle have revealed new viral kinetic patterns that have not been observed with IFN±RBV. Very recently, studies have showed that single nucleotide polymorphisms (SNPs) in the IL28B gene region were associated with race/ethnicity and with response to IFN±RBV. Here we review our current knowledge of HCV kinetics and related mathematical models during IFN±RBV and/or DAA based therapies, HCV pathogenesis, and the role of IL28B polymorphism on early HCV kinetics. Better understanding of the mode of actions of drug(s) and viral kinetics may help to develop, in the near future, new individualized therapeutic regimens that include DAAs in combination with IFN+RBV.
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http://dx.doi.org/10.1007/s11901-011-0101-7 | DOI Listing |
Sci Rep
December 2024
The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Ave., Maywood, IL, 60153, USA.
Designing and carrying out a controlled human infection (CHI) model for hepatitis C virus (HCV) is critical for vaccine development. However, key considerations for a CHI model protocol include understanding of the earliest viral-host kinetic events during the acute phase and susceptibility of the viral isolate under consideration for use in the CHI model to antiviral treatment before any infections in human volunteers can take place. Humanized mouse models lack adaptive immune responses but provide a unique opportunity to obtain quantitative understanding of early HCV kinetics and develop mathematical models to further understand viral and innate immune response dynamics during acute HCV infection.
View Article and Find Full Text PDFJ Infect Dis
December 2024
Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Background: Hepatitis C virus (HCV) infects nearly one-fourth of people with HIV (PWH). The role of direct-acting antivirals (DAAs) on immune activation in PWH and HCV is poorly understood.
Methods: We quantified plasma HCV RNA and CXCL10 in persons with HCV mono- versus HIV/HCV co-infection receiving Sofosbuvir-Velpatasvir.
Curr Protoc
November 2024
Institute of Virology, Medical University of Innsbruck, Innsbruck, Austria.
Protease inhibitors are among the most powerful antiviral drugs. They have been used successfully against viruses, such as the human immunodeficiency virus (HIV), hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Protease inhibitor screening tools are therefore important to identify inhibitors that have the potential to become antiviral drugs.
View Article and Find Full Text PDFJ Hepatol
October 2024
Emory National Primate Research Center, Emory University, Atlanta, Georgia, USA; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. Electronic address:
Background & Aims: The most recent T cell-based vaccine against HCV tested in humans failed to swing the pendulum from chronicity to resolution, despite eliciting cellular responses in most individuals. These results naturally evoke the question of whether hyperactivated responses of a single adaptive immune arm are capable of inducing HCV clearance or if coordinated efforts between antibodies and T cells are indeed necessary. Here, we sought to address this point in determining whether the suppression of antiviral T cell and IgG responses by regulatory T cells (Tregs) is a critical prerequisite of delayed viral clearance or overt chronicity.
View Article and Find Full Text PDFPLoS Pathog
October 2024
Division of Hepatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
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