Hydroxyurea Suppresses HCV Replication in Humans: A Phase I Trial of Oral Hydroxyurea in Chronic Hepatitis C Patients
| Autor: | Kazuya Sugimori, Eiji Miyajima, Nobuyuki Kato, Akito Nozaki, Masanori Ikeda, Masaaki Kondo, Manabu Morimoto, Kazushi Numata, Katsuaki Tanaka, Shin Maeda, Satoshi Morita |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Cirrhosis Hepacivirus Hepatitis C virus Administration Oral Virus Replication medicine.disease_cause Chronic liver disease Virus Hydroxycarbamide Japan medicine Humans Hydroxyurea Pharmacology (medical) Aged Nucleic Acid Synthesis Inhibitors Pharmacology biology business.industry Hepatitis C Hepatitis C Chronic Middle Aged biology.organism_classification medicine.disease Virology Infectious Diseases Hepatocellular carcinoma Cancer research RNA Viral Female business medicine.drug |
| Zdroj: | Antiviral Therapy. 15:1179-1183 |
| ISSN: | 2040-2058 1359-6535 |
| DOI: | 10.3851/imp1668 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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