Expression of Biliverdin Reductase A in peripheral blood leukocytes is associated with treatment response in HCV-infected patients

• Published in: PloS one Vol. 8; no. 3; p. e57555
• Main Authors: Subhanova, Iva, Muchova, Lucie, Lenicek, Martin, Vreman, Hendrik J, Luksan, Ondrej, Kubickova, Kristyna, Kreidlova, Miluse, Zima, Tomas, Vitek, Libor, Urbanek, Petr
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11-03-2013; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Antioxidants; Antioxidants (Nutrients); Antiviral agents; Antiviral Agents - therapeutic use; Biliverdin; Biliverdin reductase; Biochemistry; Biology; Blood; Carbon monoxide; Care and treatment; Catabolism; Chronic infection; Enzymes; Female; Gene Expression; Genes; Genotype & phenotype; Health aspects; Heme; Heme - metabolism; Heme Oxygenase (Decyclizing) - genetics; Heme Oxygenase (Decyclizing) - metabolism; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Hepacivirus; Hepatitis; Hepatitis C; Hepatitis C - drug therapy; Hepatitis C - genetics; Hepatitis C - virology; Hepatitis C virus; Hepatology; Hospitals; Humans; Infection; Infections; Interferon; Internal medicine; Laboratories; Leukocytes; Leukocytes - metabolism; Leukocytes - virology; Liver; Liver - metabolism; Liver - virology; Liver diseases; Male; Medicine; Metabolic Networks and Pathways - genetics; Middle Aged; Multivariate analysis; Oxidative stress; Oxidoreductases Acting on CH-CH Group Donors - genetics; Oxygenase; Patients; Peripheral blood; Ribonucleic acid; RNA; ROC Curve; Rodents; Therapy; Treatment Outcome; Viruses; Czech Republic
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0057555

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.
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.
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.
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.