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

doi:10.3851/IMP1668

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 journal › Article › peer-review

8 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 language	English
Pages (from-to)	1179-1183
Number of pages	5
Journal	Antiviral Therapy
Volume	15
Issue number	8
DOIs	https://doi.org/10.3851/IMP1668
Publication status	Published - 2010

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

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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 › peer-review

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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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.",

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

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AU - Kondo, Masaaki

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AU - Morita, Satoshi

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AU - Maeda, Shin

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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.

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

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