Hepatocyte Proliferation and Hepatitis C Virus Kinetics During Treatment

Dahari, Harel; Liang, Rong; Layden, TJ; Cotler, S.J.

doi:10.1038/clpt.2010.238

Cited by 3 publications

(1 citation statement)

References 5 publications

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“…These observations are interesting as they suggest that in these patients the total drug efficacy is lower than the critical drug efficacy and eventually the viral load will increase spontaneously. Snoeck et al assumed a very small maximum hepatocyte proliferation rate (doubling time=123 days) in all patients, which in part, allowed the prediction of late rebounds [31]. Other important aspects of the Snoeck et al approach in using Eq.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis C Viral Kinetics in the Era of Direct Acting Antiviral Agents and Interleukin-28B

et al. 2011

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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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Section: Introductionmentioning

confidence: 99%

Hepatitis C Viral Kinetics in the Era of Direct Acting Antiviral Agents and Interleukin-28B

et al. 2011

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Modelling hepatitis C therapy—predicting effects of treatment

Perelson

Guedj

2015

Nat Rev Gastroenterol Hepatol

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Mathematically modelling HCV RNA changes measured in patients who receive antiviral therapy has yielded many insights into the pathogenesis and effects of treatment on the virus. By determining how rapidly HCV is cleared when viral replication is interrupted by a therapy, one can deduce how rapidly the virus is produced in patients before treatment. This knowledge, coupled with estimates of the HCV mutation rate, enables one to estimate the frequency with which drug resistant variants arise. Modelling HCV also permits the deduction of antiviral agent effectiveness at blocking HCV replication from the magnitude of the initial viral decline. One can also estimate the lifespan of an HCV infected cell from the slope of the subsequent viral decline and, determine the duration of therapy needed to cure infection. Our understanding of HCV RNA decline under IFN-based therapies needs to be revised in order to understand the HCV RNA decline kinetics seen when using direct-acting antiviral agents (DAAs). In this Review, we also discuss the unresolved issues involving understanding therapies with combinations of DAAs, such as whether a sustained virological response necessarily involves elimination of all infected cells

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