title: Expression of Biliverdin Reductase A in peripheral blood leukocytes is associated with treatment response in HCV-infected patients.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) infection is associated with systemic oxidative stress. Since the heme catabolic pathway plays an important role in antioxidant protection, we attempted to assess the gene expression of key enzymes of heme catabolism, heme oxygenase 1 (HMOX1), heme oxygenase 2 (HMOX2), and biliverdin reductase A (BLVRA) in the liver and peripheral blood leukocytes (PBL) of patients chronically infected with HCV.
  
  
  METHODS
  Gene expressions (HMOX1, HMOX2, BLVRA) and HCV RNA were analyzed in PBL of HCV treatment naïve patients (n = 58) and controls (n = 55), with a subset of HCV patients having data on hepatic gene expression (n = 35). Based upon the therapeutic outcome, HCV patients were classified as either responders (n = 38) or treatment-failure patients (n = 20). Blood samples in HCV patients were collected at day 0, and week 12, 24, 36, and 48 after the initiation of standard antiviral therapy.
  
  
  RESULTS
  Compared to the controls, substantially increased BLVRA expression was detected in PBL (p<0.001) of therapeutically naïve HCV patients. mRNA levels of BLVRA in PBL closely correlated with those in liver tissue (r2 = 0.347,p = 0.03). A marked difference in BLVRA expression in PBL between the sustained responders and patients with treatment failure was detected at week 0 and during the follow-up (p<0.001). Multivariate analysis revealed that BLVRA basal expression in PBL was an independent predictor for sustained virological response (OR 15; 95% CI 1.05-214.2; P = 0.046). HMOX1/2 expression did not have any effect on the treatment outcome.
  
  
  CONCLUSIONS
  Our results suggest that patients with chronic HCV infection significantly upregulate BLVRA expression in PBL. The lack of BLVRA overexpression is associated with non-responsiveness to standard antiviral therapy; whereas, HMOX1/2 does not seem to have any predictive potential.
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. iva.subhanova@seznam.cz
authors.forename: Iva
authors.initials: I
authors.lastname: Subhanova
authors.forename: Lucie
authors.initials: L
authors.lastname: Muchova
authors.forename: Martin
authors.initials: M
authors.lastname: Lenicek
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Vreman
authors.forename: Ondrej
authors.initials: O
authors.lastname: Luksan
authors.forename: Kristyna
authors.initials: K
authors.lastname: Kubickova
authors.forename: Miluse
authors.initials: M
authors.lastname: Kreidlova
authors.forename: Tomas
authors.initials: T
authors.lastname: Zima
authors.forename: Libor
authors.initials: L
authors.lastname: Vitek
authors.forename: Petr
authors.initials: P
authors.lastname: Urbanek
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D007962:Leukocytes / Q000378:metabolism* / Q000821:virology; D008099:Liver / Q000378:metabolism / Q000821:virology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D012372:ROC Curve; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase
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