Page 19 - CIBEREHD-2015-eng

Viral Hepatitis
COORDINATOR: DR. JUAN IGNACIO ESTEBAN MUR
• The public HBV database known as CIBERHEP has gone on expanding and now has 1245 patients, 25 participating centres in nine Spanish administrative regions (822 have received Tenofovir; 408 have received Entecavir).
• The HIGH-RESOLUTION HCV SUBTYPING system based on mass sequencing and
• Research with genomic HCV replicons has enabled investigating the effect of direct-acting antivirals on the quasispecies dynamic of HCV, proving for the first time that viral fitness can condition resistance to a treatment (even against sofosbuvir) in the absence of resistance mutations.
Scientific Programmes
Molecular Phylogeny has been incorporated as a centralised diagnostic test at HUVH Hospital with an access code which gives service to the whole Catalan health service. This system has international patent WO2015001068 A1 and CIBEREHD has a partial interest in said patent.
• A procedure for detecting Resistances to Inhibitors with direct action against HCV based on massively parallel sequencing has been developed.
• Financing has been obtained for a Proposal as part of the Strategic Plan in Health for Hepatitis C 2015 in which all the groups in programme 2 are taking part (2015-2017).
• “Hepa-C”, a public HCV database owned by CIBEREHD has been consolidated. This is completely operative, over 1100 patients have been entered and it has produced presentations at congresses.
• Methodologies for genotyping and detecting mutations of resistance of HBV and HDV based on mass sequencing have been developed. Software enabling the detection of Insertions and Deletions has been installed.
• Epidemiological studies have been reinforced on HBV, HCV, HDV and HEV. Studies on nosocomial transmission of HCV have been carried out with the Health Agencies of Spanish administrative regions. In this respect a cooperative study has been completed on new HCV (acute) infections in men who have sex with male HIV+ patients by mass sequencing.
• A work on HCV+ patients receiving the transplant of a C+ virus liver has been published. Work is being done on massively parallel sequencing studies on Cholestatic patients as well as on studies on Variability of Quasispecies and progression of liver damage in patients treated with everolimus.
• We proceeded to the diagnosis of Q80K resistance mutation of HCV by means of Lightcycler with FRET probes.
• Non-invasive techniques (ARFI) for characterising hepatic fibrosis have been appraised, including approved software for analysing magnetic resonance images.
• We have continued with the “FLIP project” research on hepatocarcinoma through NASH, HCV or cryptogenic cirrhosis. European cooperation goes on in the subject of “Prevention and treatment of non-alcoholic fatty liver disease (NAFLD)”.
• Cooperation for studying vertical mother-child transmission of HCV has been reinforced.
• A line of research into epigenetic signatures between the host’s genomic DNA and HBV or HCV genomes has been consolidated, as well as studies on lncRNAs and miRNAs in biopsies of chronic hepatitis C and their implication in the progression of fibrosis and the development of hepatocarcinoma.
• New anti-HCV inhibitors (quercetin, etc.) have been characterised and the role of different receptors such as clatrine in the entry of HCV to the hepatocyte, and apolipoproteins b and e in the cell to cell transmission of HCV.
• Studies have been carried out on the effect of compounds of natural extracts on the inhibition of NS3 activity in vitro, as well as GWAS studies in patients subject to treatment with NS3 inhibitors.
• Progress has been made in the development of new techniques for HCV treatment such as the case of Synthesis of specific polyanionic carbosilane dendrimers against HCV.
• Another group of cooperative studies concerns the search for non-invasive angiogenic prognostic
CIBEREHD I Annual report 2015 I 19