Dynamics of hepatitis C under optimal therapy and sampling based analysis

DOI10.1016/J.CNSNS.2012.12.032MaRDI QIDQ375585zbMATH OpenOpenAlexFDO

Authors Gaurav Pachpute, Siddhartha P. Chakrabarty

Publication date 31 October 2013

Published in Communications in Nonlinear Science and Numerical Simulation (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1109.0615, http://www.sciencedirect.com/science/article/pii/S1007570413000038

zbMATH Keywords

Latin hypercube samplingoptimal controlstatistical testshepatitis Csteepest-gradient method

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Medical epidemiology (92C60)

Abstract: We examine two models for hepatitis C viral (HCV) dynamics, one for monotherapy with interferon (IFN) and the other for combination therapy with IFN and ribavirin. Optimal therapy for both the models is determined using the steepest gradient method, by defining an objective functional which minimizes the infected hepatocyte levels, virion population and the side-effects of the drug(s). The optimal therapy for both the models shows an initial period of high efficacy, followed by a gradual decline. The period of high efficacy coincides with a significant decrease in the infected hepatocyte levels as well as viral load, whereas the efficacy drops after liver regeneration through restored hepatocyte levels. The period of high efficacy is not altered significantly when the cost coefficients are varied, as long as the side effects are relatively small. This suggests a higher dependence of the optimal therapy on the model parameters in case of drugs with minimal side effects. We use the Latin hypercube sampling technique to randomly generate a large number of patient scenarios (i.e, model parameter sets) and study the dynamics of each set under the optimal therapy already determined. Results show an increase in the percentage of responders (as indicated by drop in viral load below detection levels) in case of combination therapy as compared to monotherapy. Statistical tests performed to study the correlations between sample parameters and the time required for the viral load to fall below detection level, show a strong monotonic correlation with the death rate of infected hepatocytes, identifying it to be an important factor in deciding individual drug regimens.

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• Optimal control of an HIV model with CTL cells and latently infected cells
• Prediction of long-term treatment outcome in HCV following 24 day PEG-IFN alpha-2b therapy using population pharmacokinetic-pharmacodynamic mixture modeling and classification analysis
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• scientific article; zbMATH DE number 7055508 (Why is no real title available?)
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