Abstract
Background: HCV is the main causative agent of chronic liver disease, which could progress to liver cirrhosis and hepatocellular carcinoma. By using a recently developed genome-length HCV RNA replication reporter assay system, we found that hydroxyurea (HU), an inhibitor of DNA synthesis, inhibited HCV RNA replication. Methods: To test the hypothesis that HU suppresses HCV replication in humans, we conducted a Phase I trial involving Japanese patients with chronic hepatitis C (CHC) and investigated the safety and effectiveness of a 4-week course of oral HU. Results: A total of nine patients were treated with an HU dose level of 500 mg three times daily. Dose-limiting toxicity was not observed at this dose level. Of the nine patients, eight exhibited a moderate decrease in serum HCV RNA levels during the trial. A decrease in HCV RNA levels to nadir levels was achieved for the eight patients (median -0.27 log10 IU/ml [range -0.08- -0.44]) at various times during the 4 weeks after therapy initiation. Conclusions: The results of this Phase I trial suggest that HU has potential as an anti-HCV agent that could be effective for the treatment of CHC patients.
| Original language | English |
|---|---|
| Pages (from-to) | 1179-1183 |
| Number of pages | 5 |
| Journal | Antiviral Therapy |
| Volume | 15 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2010 |
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ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases
Cite this
Hydroxyurea suppresses HCV replication in humans : A Phase I trial of oral hydroxyurea in chronic hepatitis C patients. / Nozaki, Akito; Numata, Kazushi; Morimoto, Manabu; Kondo, Masaaki; Sugimori, Kazuya; Morita, Satoshi; Miyajima, Eiji; Ikeda, Masanori; Kato, Nobuyuki; Maeda, Shin; Tanaka, Katsuaki.
In: Antiviral Therapy, Vol. 15, No. 8, 2010, p. 1179-1183.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hydroxyurea suppresses HCV replication in humans
T2 - A Phase I trial of oral hydroxyurea in chronic hepatitis C patients
AU - Nozaki, Akito
AU - Numata, Kazushi
AU - Morimoto, Manabu
AU - Kondo, Masaaki
AU - Sugimori, Kazuya
AU - Morita, Satoshi
AU - Miyajima, Eiji
AU - Ikeda, Masanori
AU - Kato, Nobuyuki
AU - Maeda, Shin
AU - Tanaka, Katsuaki
PY - 2010
Y1 - 2010
N2 - Background: HCV is the main causative agent of chronic liver disease, which could progress to liver cirrhosis and hepatocellular carcinoma. By using a recently developed genome-length HCV RNA replication reporter assay system, we found that hydroxyurea (HU), an inhibitor of DNA synthesis, inhibited HCV RNA replication. Methods: To test the hypothesis that HU suppresses HCV replication in humans, we conducted a Phase I trial involving Japanese patients with chronic hepatitis C (CHC) and investigated the safety and effectiveness of a 4-week course of oral HU. Results: A total of nine patients were treated with an HU dose level of 500 mg three times daily. Dose-limiting toxicity was not observed at this dose level. Of the nine patients, eight exhibited a moderate decrease in serum HCV RNA levels during the trial. A decrease in HCV RNA levels to nadir levels was achieved for the eight patients (median -0.27 log10 IU/ml [range -0.08- -0.44]) at various times during the 4 weeks after therapy initiation. Conclusions: The results of this Phase I trial suggest that HU has potential as an anti-HCV agent that could be effective for the treatment of CHC patients.
AB - Background: HCV is the main causative agent of chronic liver disease, which could progress to liver cirrhosis and hepatocellular carcinoma. By using a recently developed genome-length HCV RNA replication reporter assay system, we found that hydroxyurea (HU), an inhibitor of DNA synthesis, inhibited HCV RNA replication. Methods: To test the hypothesis that HU suppresses HCV replication in humans, we conducted a Phase I trial involving Japanese patients with chronic hepatitis C (CHC) and investigated the safety and effectiveness of a 4-week course of oral HU. Results: A total of nine patients were treated with an HU dose level of 500 mg three times daily. Dose-limiting toxicity was not observed at this dose level. Of the nine patients, eight exhibited a moderate decrease in serum HCV RNA levels during the trial. A decrease in HCV RNA levels to nadir levels was achieved for the eight patients (median -0.27 log10 IU/ml [range -0.08- -0.44]) at various times during the 4 weeks after therapy initiation. Conclusions: The results of this Phase I trial suggest that HU has potential as an anti-HCV agent that could be effective for the treatment of CHC patients.
UR - http://www.scopus.com/inward/record.url?scp=78650991081&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650991081&partnerID=8YFLogxK
U2 - 10.3851/IMP1668
DO - 10.3851/IMP1668
M3 - Article
C2 - 21149925
AN - SCOPUS:78650991081
VL - 15
SP - 1179
EP - 1183
JO - Antiviral Therapy
JF - Antiviral Therapy
SN - 1359-6535
IS - 8
ER -