Heme Catabolic Pathway in Chronic Hepatitis C
Project goals
Heme oxygenase (HMOX), an enzyme induced in response to oxidative stress, catalyzes degradation of pro-oxidative heme to carbon monoxide (CO), iron and biliverdin, which is reduced to bilirubin by biliverdin reductase A (BVRA). Hepatic expression of HMOX is reduced during hepatitis C infection (HCV) in vivo. Biliverdin seems to interfere with HCV replication in vitro. Recently, in the retrospective pilot study, we have found significant association between BVRA expression in PBMC of HCV infected patients prior to antiviral treatment and the response to the therapy. In the proposed prospective clinical trial (registered under ID: NCT01112033), we will study the association of the pre-treatment expression of BVRA in the liver and PBMC with viral clearance, disease progression and treatment response. Analyzing BVRA expression in PBMC might become a promising diagnostic tool. This simple non-invasive test would help to predict which patients will respond to standard antiviral therapy.
Keywords
hepatitis C virusbiliverdin reductasegene expressionoxidative stress
Public support
Provider
Ministry of Health
Programme
Ministry of Health?s Departmental Research and Development Programme III
Call for proposals
VaV pro Ministerstvo zdravotnictví III 3 (SMZ0201201)
Main participants
—
Contest type
VS - Public tender
Contract ID
NT13092-4/2012
Alternative language
Project name in Czech
Katabolická dráha hemu u chronické hepatitidy C
Annotation in Czech
V patogenezi komplikací chronické hepatitidy C hraje roli oxidační stres, indukovaný virem hepatitidy C (HCV). Hemoxygenáza (HMOX), katalyzující degradaci hemu na oxid uhelnatý, železo a biliverdin, který je biliverdinreduktázou A (BVRA) redukován na bilirubin, chrání játra před oxidačním stresem. Dosud bylo prokázáno, že u HCV infekce je exprese HMOX v jaterní tkáni snížena a že biliverdin in vitro interferuje s replikací viru. V naší pilotní retrospektivní studii jsme zjistili, že exprese BVRA v PBMC může predikovat odpověď pacientů s HCV na standardní terapii. V navrhované prospektivní klinické studii (registrované pod ID: NCT01112033) budeme hledat asociaci exprese BVRA před zahájením léčby v jaterní tkáni a PBMC s eliminací viru, histologickým nálezem a s odpovědí na terapii. Pokud studie potvrdí naše předběžná data, analýza exprese BVRA v PBMC by se mohla stát jednoduchým neinvazivním testem, který by mohl přispět k predikci odpovídavosti na protivirovou terapii ještě před jejím zahájením.
Scientific branches
R&D category
NV - Nonindustrial research (Applied research excluded Industrial research)
CEP classification - main branch
FP - Other medical fields
CEP - secondary branch
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CEP - another secondary branch
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30106 - Anatomy and morphology (plant science to be 1.6)
30107 - Medicinal chemistry
30108 - Toxicology
30109 - Pathology
30221 - Critical care medicine and Emergency medicine
30223 - Anaesthesiology
30224 - Radiology, nuclear medicine and medical imaging
30225 - Allergy
30226 - Rheumatology
30227 - Geriatrics and gerontology
30229 - Integrative and complementary medicine (alternative practice systems)
30230 - Other clinical medicine subjects
30307 - Nursing
30308 - Nutrition, Dietetics
30309 - Tropical medicine
30310 - Parasitology
30311 - Medical ethics
30312 - Substance abuse
30501 - Forensic science
30502 - Other medical science
Completed project evaluation
Provider evaluation
V - Vynikající výsledky projektu (s mezinárodním významem atd.)
Project results evaluation
The submitted final report of the reasearch project is high-quality one. Authors found that patients suffering ftom chronic hepatitis C had significantly higher expresion of mRNA biliverdin reductase A of leukocytes compared to heathy controls.
Solution timeline
Realization period - beginning
Apr 1, 2012
Realization period - end
Dec 31, 2015
Project status
U - Finished project
Latest support payment
Mar 20, 2015
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP16-MZ0-NT-U/02:1
Data delivery date
Dec 19, 2016
Finance
Total approved costs
4,323 thou. CZK
Public financial support
4,323 thou. CZK
Other public sources
0 thou. CZK
Non public and foreign sources
0 thou. CZK
Basic information
Recognised costs
4 323 CZK thou.
Public support
4 323 CZK thou.
100%
Provider
Ministry of Health
CEP
FP - Other medical fields
Solution period
01. 04. 2012 - 31. 12. 2015