Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin: A metabolomics analysis

Takafumi Saito, Masahiro Sugimoto, Kaori Igarashi, Kaori Saito, Li Shao, Tomohiro Katsumi, Kyoko Tomita, Chikako Sato, Kazuo Okumoto, Yuko Nishise, Hisayoshi Watanabe, Masaru Tomita, Yoshiyuki Ueno, Tomoyoshi Soga

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21 Citations (Scopus)


Objectives Serum samples from patients with chronic hepatitis C were subjected to metabolomics analysis to clarify the pretreatment characteristics of their metabolites and also changes in specific metabolites resulting from antiviral therapy with pegylated interferon plus ribavirin (PegIFN/RBV). Materials/Methods The serum levels of low-molecular-weight metabolites in the twenty patients before and 24 weeks after completion of PegIFN/RBV therapy were analyzed using capillary electrophoresis and liquid chromatography-mass spectrometry. Results Ten patients showed a non-virological response (NVR) and 10 achieved a sustained virological response (SVR) with eradication of viremia. The pretreatment levels of tryptophan were significantly higher in the patients of SVR than in those of NVR (p = 0.010). The area under the curve (AUC) value of tryptophan calculated from the receiver operating characteristic (ROC) curve for discriminating SVR from NVR was 0.84 (95% confidential interval, 0.66-1.02, p = 0.010). The ROC curve of multiple logistic regression model incorporating the pretreatment levels of tryptophan and γ-glutamate-arginine showed that the AUC value was highly significant (AUC = 0.92, 95% confidential interval, 0.79-1.05, p = 0.002). Twenty four weeks after completion of treatment, the levels of γ-glutamyl dipeptides, glutamic acid, 5-oxoproline, glucosamine and methionine sulfoxide were decreased, whereas those of 5-methoxy-3- indoleacetate, glutamine, kynurenine and lysine were increased significantly (p < 0.05) in both the NVR and SVR patients. Conclusions The pretreatment serum levels of certain metabolites including tryptophan are associated with the response to PegIFN/RBV therapy. PegIFN/RBV therapy can ameliorate the oxidative stress responsible for glutathione metabolism.

Original languageEnglish
Pages (from-to)1577-1586
Number of pages10
JournalMetabolism: clinical and experimental
Issue number11
Publication statusPublished - 2013 Nov


  • Glutathione
  • HCV
  • Metabolome
  • Oxidative stress

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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