Researchers
reported results from a model of HCV RNA decline in the July 2007 issue of Hepatology.
According
to the authors, a triphasic decline consists of a first phase (1-2 days) with
rapid HCV viral load decline, followed by a "shoulder phase" (4-28 days)
in which HIV RNA decays slowly or remains constant, and then a third phase of
renewed viral load decay.
By
including the proliferation of both uninfected and infected cells, the investigators
showed that a viral kinetic model can account for a triphasic HCV RNA decay. The
model predicted that a triphasic decline would occur only in patients in whom
a majority of hepatocytes are infected before starting therapy.
The
"shoulder phase" does not represent the intrinsic death rate of infected
cells, the authors noted, but rather the third phase slope is close to the intrinsic
death rate of infected hepatocytes when overall drug efficacy is close to 1.
"Triphasic
responses can be predicted from a generalization of existent viral kinetic models
through the inclusion of homeostatic proliferation of hepatocytes," they
concluded. "This generalized model can also explain the viral kinetics seen
in flat partial responders."
Finally,
they added, "the enhanced third phase in patients treated with interferon
alpha in combination with ribavirin versus patients treated with interferon alpha
alone can be explained by a mutagenic effect of ribavirin against HCV."
08/10/07
Reference H
Dahari, RM Ribeiro, AS Perelson. Triphasic decline of hepatitis C virus RNA during
antiviral therapy. Hepatology 46(1): 16-21. July 2007.
