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

Research output: Contribution to journalArticle

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Abstract

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
Volume62
Issue number11
DOIs
Publication statusPublished - 2013 Nov

Fingerprint

Metabolomics
Ribavirin
Chronic Hepatitis C
Interferons
Tryptophan
Area Under Curve
Serum
arginine glutamate
ROC Curve
glutamyl-glutamic acid
Logistic Models
Pyrrolidonecarboxylic Acid
Kynurenine
Therapeutics
Dipeptides
Viremia
Glucosamine
Capillary Electrophoresis
Glutamine
Liquid Chromatography

Keywords

  • CE-TOFMS
  • Glutathione
  • HCV
  • Metabolome
  • Oxidative stress

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin : A metabolomics analysis. / Saito, Takafumi; Sugimoto, Masahiro; Igarashi, Kaori; Saito, Kaori; Shao, Li; Katsumi, Tomohiro; Tomita, Kyoko; Sato, Chikako; Okumoto, Kazuo; Nishise, Yuko; Watanabe, Hisayoshi; Tomita, Masaru; Ueno, Yoshiyuki; Soga, Tomoyoshi.

In: Metabolism: Clinical and Experimental, Vol. 62, No. 11, 11.2013, p. 1577-1586.

Research output: Contribution to journalArticle

Saito, T, Sugimoto, M, Igarashi, K, Saito, K, Shao, L, Katsumi, T, Tomita, K, Sato, C, Okumoto, K, Nishise, Y, Watanabe, H, Tomita, M, Ueno, Y & Soga, T 2013, 'Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin: A metabolomics analysis', Metabolism: Clinical and Experimental, vol. 62, no. 11, pp. 1577-1586. https://doi.org/10.1016/j.metabol.2013.07.002
Saito, Takafumi ; Sugimoto, Masahiro ; Igarashi, Kaori ; Saito, Kaori ; Shao, Li ; Katsumi, Tomohiro ; Tomita, Kyoko ; Sato, Chikako ; Okumoto, Kazuo ; Nishise, Yuko ; Watanabe, Hisayoshi ; Tomita, Masaru ; Ueno, Yoshiyuki ; Soga, Tomoyoshi. / Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin : A metabolomics analysis. In: Metabolism: Clinical and Experimental. 2013 ; Vol. 62, No. 11. pp. 1577-1586.
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T1 - Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin

T2 - A metabolomics analysis

AU - Saito, Takafumi

AU - Sugimoto, Masahiro

AU - Igarashi, Kaori

AU - Saito, Kaori

AU - Shao, Li

AU - Katsumi, Tomohiro

AU - Tomita, Kyoko

AU - Sato, Chikako

AU - Okumoto, Kazuo

AU - Nishise, Yuko

AU - Watanabe, Hisayoshi

AU - Tomita, Masaru

AU - Ueno, Yoshiyuki

AU - Soga, Tomoyoshi

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

KW - CE-TOFMS

KW - Glutathione

KW - HCV

KW - Metabolome

KW - Oxidative stress

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