A pilot study of combination therapy with initial high-dose interferon and amantadine hydrochloride for patients with chronic hepatitis C with the genotype 1b virus.
OBJECTIVE
Interferon monotherapy for patients with chronic hepatitis C has been suboptimal. We studied the effect of the combination therapy of an initial high-dose of interferon and amantadine.


METHODS
We investigated the virological response of 20 patients with naive chronic hepatitis C with a high viral load of the genotype 1b virus. Seven patients were administered 6MU of interferon-beta once daily for 6 weeks and then thrice weekly for 20 weeks, and 13 were administered 6 MU of interferon-beta daily for 4 or 6 weeks and then 10 MU of natural interferon-alpha thrice weekly for 22 or 20 weeks. All patients were treated with amantadine hydrochloride (100 mg/day) for 26 weeks during interferon administration.


RESULTS
The complete response, transient response and no response rate were 15.0%, 60.0%, and 25%, respectively. After daily administration of interferon-beta intravenously, 19 patients (95.0%) showed negative tests for serum HCV-RNA by the polymerase chain reaction method. At the end of treatment, the serum HCV-RNA was not detected in any patients treated with daily interferon-beta and intermittent interferon-alpha with amantadine. At 6-month follow-up, three patients had eradicated HCV-RNA, who were in the group of daily interferon-beta and intermittent interferon-alpha with amantadine. In the patients treated with daily interferon-beta and intermittent interferon-alpha with amantadine, the complete response, transient response and no response rates were 23.1%,-76.9% and 0%, respectively.


CONCLUSIONS
These findings suggest that the combination of an initial high-dose interferon and amantadine shows promising effects on the eradication of HCV-RNA in the chronic hepatitis C patients with a high viral load of the genotype 1b virus.
Uyama
Hirokazu
H
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Enomoto
Hirayuki
H
Kishima
Yoshihiko
Y
Yamamoto
Mitsunari
M
Yoshida
Kenya
K
Okuda
Yorihide
Y
Hirotani
Tomonori
T
Kuroda
Toshifumi
T
Ito
Hiroaki
H
Matsuda
Masahiro
M
Terabayashi
Minoru
M
Noguchi
Sanai
S
Kawase
Ichiro
I
Nakamura
Hideji
H
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000547:Amantadine / Q000008:administration & dosage* / Q000009:adverse effects; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D016899:Interferon-beta / Q000008:administration & dosage* / Q000009:adverse effects; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D016899:Interferon-beta; D000547:Amantadine