In:
Antiviral Therapy, SAGE Publications, Vol. 11, No. 2 ( 2006-02), p. 197-212
Abstract:
Using a multiphase bio-mathematical model, we studied the dynamics of hepatitis B virus (HBV) infection in 72 HBeAg-negative patients who received 48 weeks of either lamivudine (3TC; 25 patients); pegylated interferon-α2a (peg-IFN-α2a) 180 mg weekly plus 3TC (23 patients), or peg-IFN-α2a 180 mg weekly plus placebo (24 patients). During the first month of therapy most of the 3TC -/+ peg-IFN-α2a treated patients showed a multiphase decay of viral load: during the first two phases, where we hypothesized a direct inhibition of virus production, the mean viral production per infected cell was reduced by 2.22 log 10 and 2.36 log 10 , respectively. At variance, peg-IFN-α2a treated patients had a biphasic profile: the first phase HBV DNA decline was slower than that observed in 3TC patients (mean HBV DNA t 1/2 =1.6 ±1.1 days and 9.5 ±3.0 h, respectively) and the direct antiviral effect reduced virus production by 1.14 log 10 From day 14 onwards (third or second phase according to multi- or biphasic patterns), HBV DNA declined mainly because of the infected hepatocyte clearance that slowed down in approximately 50% of the patients from day 35, possibly because of a negative feedback on the immune system activity. Computing the number of infected cells at the end of therapy we found that peg-IFN-α2a and 3TC monotherapy determined a similar reduction of infected hepatocytes (mean: -3.3 log 10 ), whereas there was a greater reduction in combination therapy patients (-5.0 versus -3.3 log 10 , P=0.039). In conclusion, peg-IFN-α2a, in spite of having direct antiviral activity lower than that of 3TC, achieved a comparable reduction of infected hepatocytes, possibly because of a higher infected cell clearance rate.
Type of Medium:
Online Resource
ISSN:
1359-6535
,
2040-2058
DOI:
10.1177/135965350601100201
Language:
English
Publisher:
SAGE Publications
Publication Date:
2006
detail.hit.zdb_id:
2118396-X
SSG:
15,3
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