Different turnover rate of hepatitis C virus clearance by different treatment regimen using interferon-beta.
OBJECTIVE
Since patients with high viral load and HCV subtype 1b are known to respond poorly to interferon (IFN) therapy, the viral dynamics of HCV RNA after initiation of interferon therapy were examined in the present study with respect to two different administration regimens, once vs. twice a day.


METHODS
Twenty-two patients with chronic hepatitis C confirmed by liver biopsy and with >1 Meq/ml of HCV RNA and HCV subtype 1b were randomly assigned to two different IFN administration regimens (6 million units of IFN once a day or 3 million units of IFN twice a day), and the serum HCV RNA level was serially measured.


RESULTS
Graphs of HCV RNA levels vs. treatment time showed an initial rapid fall, followed by a slower clearance phase. Fitting the data to a model for HCV decay proposed by Neumann et al. showed that the treatment efficacy was significantly higher with twice daily administration. Negativity for HCV RNA measured by Amplicor assay in the twice-a-day administration group was 18%, 73% and >89% at 1, 2 and 3 weeks, respectively, in contrast to 0%, 0%, and 18%, respectively, with once-a-day administration. However, a significant reduction of platelet count and albumin level, a marked increase in serum aspartate aminotransferase/alanine aminotransferase, and a high incidence of renal toxicity (proteinuria) were found in patients receiving IFN twice a day in comparison with those receiving it once a day.


CONCLUSIONS
The twice-a-day administration of IFN accelerated the clearance of HCV RNA from serum, leading to a more efficient virological response for patients with chronic hepatitis C, but with a high rate of renal toxicity.
Shiratori
Y
Y
Department of Internal Medicine, University of Tokyo, Japan.
Perelson
A S
AS
Weinberger
L
L
Imazeki
F
F
Yokosuka
O
O
Nakata
R
R
Ihori
M
M
Hirota
K
K
Ono
N
N
Kuroda
H
H
Motojima
T
T
Nishigaki
M
M
Omata
M
M
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D012367:RNA, Viral; D016899:Interferon-beta