Hydroxyurea suppresses HCV replication in humans: A Phase I trial of oral hydroxyurea in chronic hepatitis C patients

Akito Nozaki, Kazushi Numata, Manabu Morimoto, Masaaki Kondo, Kazuya Sugimori, Satoshi Morita, Eiji Miyajima, Masanori Ikeda, Nobuyuki Kato, Shin Maeda, Katsuaki Tanaka

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 languageEnglish
Pages (from-to)1179-1183
Number of pages5
JournalAntiviral Therapy
Volume15
Issue number8
DOIs
Publication statusPublished - 2010

Fingerprint

Hydroxyurea
Chronic Hepatitis C
RNA
Nucleic Acid Synthesis Inhibitors
Liver Cirrhosis
Liver Diseases
Hepatocellular Carcinoma
Chronic Disease
Genome
Safety
Therapeutics
Serum

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Nozaki, A., Numata, K., Morimoto, M., Kondo, M., Sugimori, K., Morita, S., ... Tanaka, K. (2010). Hydroxyurea suppresses HCV replication in humans: A Phase I trial of oral hydroxyurea in chronic hepatitis C patients. Antiviral Therapy, 15(8), 1179-1183. https://doi.org/10.3851/IMP1668

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 journalArticle

Nozaki, A, Numata, K, Morimoto, M, Kondo, M, Sugimori, K, Morita, S, Miyajima, E, Ikeda, M, Kato, N, Maeda, S & Tanaka, K 2010, 'Hydroxyurea suppresses HCV replication in humans: A Phase I trial of oral hydroxyurea in chronic hepatitis C patients', Antiviral Therapy, vol. 15, no. 8, pp. 1179-1183. https://doi.org/10.3851/IMP1668
Nozaki, Akito ; Numata, Kazushi ; Morimoto, Manabu ; Kondo, Masaaki ; Sugimori, Kazuya ; Morita, Satoshi ; Miyajima, Eiji ; Ikeda, Masanori ; Kato, Nobuyuki ; Maeda, Shin ; Tanaka, Katsuaki. / Hydroxyurea suppresses HCV replication in humans : A Phase I trial of oral hydroxyurea in chronic hepatitis C patients. In: Antiviral Therapy. 2010 ; Vol. 15, No. 8. pp. 1179-1183.
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