title: Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin: a metabolomics analysis.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  The serum levels of low-molecular-weight metabolites in the twenty patients before and 24weeks 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.
authors: Department of Gastroenterology, Yamagata University School of Medicine, Yamagata 990-9585, Japan. Electronic address: tasaitoh@med.id.yamagata-u.ac.jp.
authors: Takafumi
authors: T
authors: Saito
authors: Masahiro
authors: M
authors: Sugimoto
authors: Kaori
authors: K
authors: Igarashi
authors: Kaori
authors: K
authors: Saito
authors: Li
authors: L
authors: Shao
authors: Tomohiro
authors: T
authors: Katsumi
authors: Kyoko
authors: K
authors: Tomita
authors: Chikako
authors: C
authors: Sato
authors: Kazuo
authors: K
authors: Okumoto
authors: Yuko
authors: Y
authors: Nishise
authors: Hisayoshi
authors: H
authors: Watanabe
authors: Masaru
authors: M
authors: Tomita
authors: Yoshiyuki
authors: Y
authors: Ueno
authors: Tomoyoshi
authors: T
authors: Soga
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001622:Betaine / Q000031:analogs & derivatives* / Q000097:blood; D002331:Carnitine / Q000097:blood*; D002853:Chromatography, Liquid; D004359:Drug Therapy, Combination; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D025341:Principal Component Analysis; D012254:Ribavirin / Q000627:therapeutic use*; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome; D014364:Tryptophan / Q000097:blood; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001622:Betaine; D011092:Polyethylene Glycols; C002889:gamma-butyrobetaine; D012254:Ribavirin; D014364:Tryptophan; D007372:Interferons; C004946:glycocyamine; D002331:Carnitine; D005998:Glycine
keywords: ALT; AUC; CE-TOFMS; Glutathione; HCC; HCV; IDO; IFN; IL; MLR; MRM; Metabolome; NVR; Oxidative stress; PC; PegIFN/RBV; ROC; ROS; SVR; alanine aminotransferase; area under the curve; capillary electrophoresis–time-of-flight mass spectrometry; hepatitis C virus; hepatocellular carcinoma; indoleamine 2,3-dioxygenase; interferon; interleukin; multiple logistic regression; multiple reaction monitoring; non-virological response; pegylated interferon plus ribavirin; principal component; reactive oxygen species; receiver operating characteristic; sustained virological response