Hepatitis C viral kinetics in special populations

Abstract

Mathematical models of hepatitis C viral (HCV) kinetics provide a means of estimating the antiviral effectiveness of therapy, the rate of virion clearance and the rate of loss of HCV-infected cells. They have also proved useful in evaluating the extrahepatic contribution to HCV plasma viremia and they have suggested mechanisms of action for both interferon-α and ribavirin. Viral kinetic models can explain the observed HCV RNA profiles under treatment, e.g., flat partial response, biphasic and triphasic viral decay and viral rebound. Current therapy with (pegylated) interferon-α and ribavirin has a poorer success in patients having insulin resistance, hepatic fibrosis, African American ethnicity, HCV/HIV-coinfection, HCV genotype-1 and high baseline viral load. The use of mathematical modeling and statistical analysis of experimental data have been useful in understanding some of these treatment obstacles.

Hepatitis C virus viral kinetics during α-2a or α-2b pegylated interferon plus ribavirin therapy in liver transplant recipients with different immunosuppression regimes

“…35 In contrast, in our LT patients, the only potential correlate with ETVR was viral decline at week 12, probably because delayed declines, as seen before in some non-immunosuppressed 24,[36][37][38][39] and in HIV/HCV coinfected patients. 13,27,29,33 Finally, we found no significant influence of donor/recipient IL28B rs12979860 allele combinations, although the small number of patients analysed may preclude confirming the significant associations found in other studies. 40,41 The fact that treatment efficacies during the first few days of treatment were significantly lower (0-26%) than those reported in immunocompetent patients is consistent with previous observations on other monoinfected 30,37 and, especially, on HIV-coinfected individuals.…”

“…Fig. 1 summarizes the viral load kinetic profiles, classified as biphasic, triphasic, partial, or null responses, as described 13 . In 11 patients, viral load actually increased during the first 6 h after the first dose of treatment.…”

“…[11][12][13] There are few studies examining HCV viral load declines in cadaveric [14][15][16] or living-donor 17 transplant recipients and, to the best of our knowledge, no study is yet available on the early viral kinetics in LT patients receiving peg-IFN-␣ under different immunosupression regimes.…”

Modeling Subgenomic Hepatitis C Virus RNA Kinetics during Treatment with Alpha Interferon

“…It is known that different HCV genotypes exhibit differential sensitivity to IFN-␣ treatment and produce distinct liver pathologies (4,15,18). We used the HCV genotype-1b clone B replicon for our studies as it is a commonly used HCV replicon, which we previously used to mathematically model subgenomic HCV replication from transfection to steady state (6); however, similarly detailed modeling of other HCV genotypes and comparison of their IFN-␣ inhibition kinetics might reveal the basis of the distinct IFN-␣ responsiveness exhibited by the different HCV genotypes in patients.…”

“…Note that this equation is the same as equation 2 except that in equation 2 is replaced by the expression ϭ /(1 Ϫ ε in ) in equation 4. However, if we use equation 4 to fit the experimental data, we obtain the parameter estimates of a ε in of 0.972, of 0.027 day Ϫ1 , and t 0 of 9.5 h ( Table 2).…”