Ribavirin concentration in the later stages of 48 week pegylated interferon-α2b plus ribavirin therapy for chronic hepatitis C is useful for predicting virological response

Norihiro Furusyo, Murata Masayuki, Eiichi Ogawa, Kazuhiro Toyoda, Takeshi Ihara, Hiroaki Ikezaki, Takeo Hayashi, Tsunehisa Koga, Mosaburo Kainuma, Jun Hayashi

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Abstract

Objectives: The current standard of care for chronic hepatitis C patients is a pegylated interferon-α plus ribavirin combination treatment. This study was carried out to determine the relationship between ribavirin concentration in the later stages of treatment and virological relapse. Patients and methods: Serum ribavirin concentration of 183 chronic hepatitis C patients (genotype 1) treated with pegylated interferon-α2b plus ribavirin for 48 weeks was prospectively measured by HPLC at weeks 4, 12, 24, 36 and 48. Patients with undetectable serum hepatitis C virus (HCV) RNA 24 weeks after the end of treatment were designated as having sustained virological response (SVR). Patients with undetectable HCV RNA during the treatment but with virological relapse after the end of treatment were designated relapse. Results: The mean ribavirin concentration at each testing point of patients with SVR (1401, 1725, 1803, 1811 and 1901 ng/mL) was significantly higher than that of relapse patients (998, 704, 607, 643 and 654 ng/mL) at weeks 4, 12, 24, 36 and 48, respectively (all P<0.001). Multivariate regression analysis for relapse extracted ribavirin concentration at week 36, but not cumulative ribavirin dosage. The cut-off value by receiver operating curve analysis for predicting a relapse was 1503 and 1562 ng/mL at weeks 36 and 48, respectively. Conclusions: Ribavirin concentration in the later stages of treatment is an important marker of viral relapse.

Original languageEnglish
Article numberdkr034
Pages (from-to)1127-1139
Number of pages13
JournalJournal of Antimicrobial Chemotherapy
Volume66
Issue number5
DOIs
Publication statusPublished - May 1 2011

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Ribavirin
Chronic Hepatitis C
Interferons
Recurrence
Therapeutics
Hepacivirus
RNA
Standard of Care
Serum
Multivariate Analysis
Biomarkers
Genotype
High Pressure Liquid Chromatography
Regression Analysis

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Ribavirin concentration in the later stages of 48 week pegylated interferon-α2b plus ribavirin therapy for chronic hepatitis C is useful for predicting virological response. / Furusyo, Norihiro; Masayuki, Murata; Ogawa, Eiichi; Toyoda, Kazuhiro; Ihara, Takeshi; Ikezaki, Hiroaki; Hayashi, Takeo; Koga, Tsunehisa; Kainuma, Mosaburo; Hayashi, Jun.

In: Journal of Antimicrobial Chemotherapy, Vol. 66, No. 5, dkr034, 01.05.2011, p. 1127-1139.

Research output: Contribution to journalArticle

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abstract = "Objectives: The current standard of care for chronic hepatitis C patients is a pegylated interferon-α plus ribavirin combination treatment. This study was carried out to determine the relationship between ribavirin concentration in the later stages of treatment and virological relapse. Patients and methods: Serum ribavirin concentration of 183 chronic hepatitis C patients (genotype 1) treated with pegylated interferon-α2b plus ribavirin for 48 weeks was prospectively measured by HPLC at weeks 4, 12, 24, 36 and 48. Patients with undetectable serum hepatitis C virus (HCV) RNA 24 weeks after the end of treatment were designated as having sustained virological response (SVR). Patients with undetectable HCV RNA during the treatment but with virological relapse after the end of treatment were designated relapse. Results: The mean ribavirin concentration at each testing point of patients with SVR (1401, 1725, 1803, 1811 and 1901 ng/mL) was significantly higher than that of relapse patients (998, 704, 607, 643 and 654 ng/mL) at weeks 4, 12, 24, 36 and 48, respectively (all P<0.001). Multivariate regression analysis for relapse extracted ribavirin concentration at week 36, but not cumulative ribavirin dosage. The cut-off value by receiver operating curve analysis for predicting a relapse was 1503 and 1562 ng/mL at weeks 36 and 48, respectively. Conclusions: Ribavirin concentration in the later stages of treatment is an important marker of viral relapse.",
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AU - Ihara, Takeshi

AU - Ikezaki, Hiroaki

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AU - Koga, Tsunehisa

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