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This CellML file was generated on 12/02/2010 at 2:55:04 at p.m. using:

COR (0.9.31.1333)
Copyright 2002-2010 Dr Alan Garny
http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk

CellML 1.0 was used to generate this model
http://www.cellml.org/
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				<title>Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy</title>
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					<firstname>Catherine</firstname>
					<surname>Lloyd</surname>
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				<para>ABSTRACT: To better understand the dynamics of hepatitis C virus and the antiviral effect of interferon-alpha-2b (IFN), viral decline in 23 patients during therapy was analyzed with a mathematical model. The analysis indicates that the major initial effect of IFN is to block virion production or release, with blocking efficacies of 81, 95, and 96% for daily doses of 5, 10, and 15 million international units, respectively. The estimated virion half-life (t1/2) was, on average, 2.7 hours, with pretreatment production and clearance of 10(12) virions per day. The estimated infected cell death rate exhibited large interpatient variation (corresponding t1/2 = 1.7 to 70 days), was inversely correlated with baseline viral load, and was positively correlated with alanine aminotransferase levels. Fast death rates were predictive of virus being undetectable by polymerase chain reaction at 3 months. These findings show that infection with hepatitis C virus is highly dynamic and that early monitoring of viral load can help guide therapy.     
</para>
				<para>
The original paper reference is cited below:
</para>
				<para>
Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy, Avidan U. Neumann, Nancy P. Lam, Harel Dahari, David R. Gretch, Thelma E. Wiley, Thomas J. Layden, and Alan S. Perelson, 1998, <emphasis>Science</emphasis>, 282, 103-107.  <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/9756471">PubMed ID: 9756471</ulink>
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					<caption>Schematic diagram of the viral dynamics of Hepatitis C <emphasis>in vivo</emphasis>.</caption>
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      <variable name="eta" units="dimensionless" public_interface="in"/>
      <variable name="V" units="dimensionless" public_interface="in"/>
      <variable name="beta" units="first_order_rate_constant" public_interface="in"/>
      <variable name="time" units="day" public_interface="in"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>T</ci>
            </apply>
			<apply>
               <minus/>
			   <ci>s</ci>
               <apply>
                  <plus/>
			      <apply>
                     <times/>
                     <ci>d</ci>
                     <ci>T</ci>
                  </apply>
				  <apply>
                     <times/>
                     <apply>
                        <minus/>
						<cn cellml:units="dimensionless">1</cn>
                        <ci>eta</ci>
					 </apply>
                     <ci>beta</ci>
					 <ci>V</ci>
					 <ci>T</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component name="infected_cells">
      <variable name="I" units="dimensionless" initial_value="0" public_interface="out"/>
      <variable name="delta" units="first_order_rate_constant" initial_value="0.5"/>
      <variable name="beta" units="first_order_rate_constant" public_interface="in"/>
      <variable name="eta" units="dimensionless" public_interface="in"/>
      <variable name="V" units="dimensionless" public_interface="in"/>
      <variable name="T" units="dimensionless" public_interface="in"/>
      <variable name="time" units="day" public_interface="in"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>I</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <apply>
                     <minus/>
                     <cn cellml:units="dimensionless">1</cn>
                     <ci>eta</ci>
                  </apply>
                  <ci>beta</ci>
                  <ci>V</ci>
                  <ci>T</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>delta</ci>
                  <ci>I</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component name="viral_load">
      <variable name="V" units="dimensionless" initial_value="9.4e6" public_interface="out"/>
      <variable name="epsilon" units="dimensionless" initial_value="0.99"/>
      <variable name="p" units="first_order_rate_constant" initial_value="100.0"/>
      <variable name="c" units="first_order_rate_constant" initial_value="5.0"/>
      <variable name="I" units="dimensionless" public_interface="in"/>
      <variable name="time" units="day" public_interface="in"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>V</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <apply>
                     <minus/>
                     <cn cellml:units="dimensionless">1</cn>
                     <ci>epsilon</ci>
                  </apply>
                  <ci>p</ci>
                  <ci>I</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>c</ci>
                  <ci>V</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component name="model_parameters">
      <variable name="beta" units="first_order_rate_constant" initial_value="3e-7" public_interface="out"/>
      <variable name="eta" units="dimensionless" initial_value="0.8" public_interface="out"/>
   </component>
   
   <connection>
      <map_components component_1="target_cells" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="infected_cells" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="viral_load" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="target_cells" component_2="viral_load"/>
      <map_variables variable_1="V" variable_2="V"/>
   </connection>
   <connection>
      <map_components component_1="infected_cells" component_2="target_cells"/>
      <map_variables variable_1="T" variable_2="T"/>
   </connection>
   <connection>
      <map_components component_1="infected_cells" component_2="viral_load"/>
      <map_variables variable_1="V" variable_2="V"/>
      <map_variables variable_1="I" variable_2="I"/>
   </connection>
   <connection>
      <map_components component_1="target_cells" component_2="model_parameters"/>
      <map_variables variable_1="beta" variable_2="beta"/>
      <map_variables variable_1="eta" variable_2="eta"/>
   </connection>
   <connection>
      <map_components component_1="infected_cells" component_2="model_parameters"/>
      <map_variables variable_1="beta" variable_2="beta"/>
      <map_variables variable_1="eta" variable_2="eta"/>
   </connection>
</model>