Linked Life Data

17596864

Source:http://linkedlifedata.com/resource/pubmed/id/17596864

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-7-3
pubmed:abstractText
When patients chronically infected with hepatitis C virus (HCV) are placed on antiviral therapy with pegylated interferon (IFN)-alpha or IFN-alpha plus ribavirin (RBV), HCV RNA generally declines in a biphasic manner. However, a triphasic decline has been reported in a subset of patients. A triphasic decline consists of a first phase (1-2 days) with rapid virus load decline, followed by a "shoulder phase" (4-28 days) in which virus load decays slowly or remains constant, and a third phase of renewed viral decay. We show that by including the proliferation of both uninfected and infected cells, a viral kinetic model can account for a triphasic HCV RNA decay. The model predicts that a triphasic decline occurs only in patients in which a majority of hepatocytes are infected before therapy. The shoulder phase does not represent the intrinsic death rate of infected cells, but rather the third phase slope is close to the intrinsic death rate of infected cells when overall drug efficacy is close to 1. CONCLUSION: Triphasic responses can be predicted from a generalization of existent viral kinetic models through the inclusion of homeostatic proliferation of hepatocytes. This generalized model can also explain the viral kinetics seen in flat partial responders. Finally, the enhanced third phase in patients treated with IFN-alpha in combination with RBV versus patients treated with IFN-alpha alone can be explained by a mutagenic effect of RBV against HCV.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16-21
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Triphasic decline of hepatitis C virus RNA during antiviral therapy.
pubmed:affiliation
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural