Larger than normal doses of interferon alpha may be needed to treat
hepatitis C virus patients with genotype 1, according to a
In those with hepatitis C virus (HCV) disease, several
pretreatment factors are predictive of response to interferon (IFN)
including baseline serum HCV RNA levels and HCV genotype. Recent
studies showed that patients with HCV genotype 1a or 1b respond
less favorably to IFN-(alpha) treatment (3 mIU tiw), with sustained
response rates of less than 10 percent to 20 percent (Mahaney et
al., Hepatology 1994;20:1405-1411; Yoshioka et al., Hepatology
"It is unknown whether a different dosing regimen of IFN-(alpha)
would result in a better-sustained response in patients infected
with HCV genotype 1, and whether serum HCV RNA can be cleared at a
faster rate with higher doses of IFN-(alpha)," researcher Nancy P.
Lam and colleagues wrote ("Dose-Dependent Acute Clearance of
Hepatitis C Genotype 1 Virus with IFN-(alpha)," Hepatology, July
To determine if the clearance of hepatitis C genotype 1 virus is
dependent on the dose of interferon alpha-2b (IFN-(alpha)2b), the
acute clearance of HCV after a single dose of either 3, 5, or 10
mIU of IFN-(alpha) was compared in patients with chronic hepatitis
C. HCV RNA levels following IFN-(alpha) administration were
At 24 hours, mean percentage serum viral reduction was 41.4
percent, 63.7 percent, and 85.5 percent for 3, 5, and 10 mIU,
respectively (P less than .001).
At 48 hours, the mean viral reduction was consistently less than
the reduction at 24 hours, averaging 22.9 percent, 61.9 percent,
and 74.3 percent, respectively (P less than .001), indicating that
the drug effect diminishes before 48 hours. Regression analysis
showed a positive correlation between dose and percent reduction of
HCV RNA levels (r= .6; P less than .001). A mathematical model
showed that such dose dependence is expected if IFN-(alpha)
partially blocks viral production.
Minimum clearance and production rates of HCV were estimated
from measurements of HCV RNA levels after the 10 mIU dose. HCV
decay followed an exponential decline with a minimum estimate of
the viral clearance rate constant of 2.8 per day, corresponding to
a virion half-life of 0.3 days or less. A minimal estimate of the
daily HCV production and clearance is 3.7x10(11) virions per day,
indicating a high rate of replication and turnover.
"These results indicate that there is a dose-dependent effect of
IFN-(alpha) in clearance of HCV genotype 1," Lam et al. wrote.
"Because the virion production rate is very rapid and because the
current recommended dose of IFN-(alpha) (3 mIU) is often
ineffective, larger doses should be considered to treat genotype
The corresponding author for this study is Nancy P. Lam,
PharmD, Department of Pharmacy Practice (M/C 886), College of
Pharmacy, The University of Illinois at Chicago, 833 S. Wood St.,
Chicago, Illinois 60612.
Source: Hepatitis Weekly, 8/18/97, p14, 2p.
Home | What is HCV | Transmission |
| Lab |
Links | Transplant |