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• Epidemiological studies focussed in HBV, HCV, HDV and recently on HVE infection have been reinforced, including nosocomial HCV transmission studies thus supporting the National Health Spanish System . In this sense, an epidemiological study is being carried out in HIV+HCV+ homosexual patients BY ultradeep pyrosequencing (Dr . X . Forns, Dr . S . Pérez del Pulgar, Dr . J . Quer, Dr . J . Gregori, Dr . JI . Esteban, Dr . J . Mallolas, Dr . M . Laguno, Dr . M . Martínez-Rebollar) .
• Collaboration in studies on liver transplant in patients with HCV infection has increased, and specifically in a study on HCV superinfection after HCV liver transplant + by UDPS; and in another study of the HCV quasispecies dynamics in liver transplant by UDPS in cholestasis patients (Dr . X . Forns, Dr . S . Pérez del Pulgar, Dr . M . Gambato, Dr . J . Quer, Dr . J . Gregori, Dr . J . I . Esteban), as well as in studies on the variability of quasispecies and progression of liver damage in patients treated with everolimus (Dr . I . Bilbao, Dr . Ll . Castells, Dr . F . Rodríguez-Frías, Dr . I . Fields-Varela, Dr . J . Quer, Dr . J . Gregori, Dr . J . I . Esteban) .
• Antiviral protocols based on lethal mutagenesis have been developed: sequential inhibitor- mutagen therapies against HCV infections (Dr . E . Domingo, Dr . C . Perales, Dr . Manolo Leal (HIV), Dr . J . I . Esteban, Dr . J . Quer, Dr . J . Gregori) .
• A collaborative paper on the use of Ribavirin in monotherapy has been published (Dr . J . Salmerón, Dr . P . Muñoz-Rueda, Dr . R . Quiles-Pérez, Dr . J . Quer, Dr . J . I . Esteban)
• Detection of the HCV resistance mutation Q80K, which is essential for determining the use of Simeprevir in patients with chronic HCV infection, has been designed and is being validated .
• We have also succeeded in using subgenomic and genomic HCV replicons to study HCV infection, replication, including the cloning of a fully replicating full-length HCV genome (Dr . X . Forns’ group), and research for the effect of anti-viral drugs on HCV quasispecies dynamics (Dr . J . Gomez and E . Domingo) . In this sense, research is being done on the response of HCV to a direct-acting antiviral such as Sofosbuvir on the genomic clone .
• Non-invasive (ARFI) techniques to characterise hepatic fibrosis, including licensed software to analyse magnetic resonance images, have been evaluated . .
• Improvement of the detection of the viral load of the HDV (Dr . García Samaniego) with the use of internal characteristic controls that have opened up field to collaborations with European groups is underway (Dr . F . Rodriguez-Frías) .
• Studies on genomic DNA polymorphisms in interferon-stimulated genes (ISGs) have reported their association as independent predictors of the response to anti-HCV treatment (Peg-IFN and ribavirin) in chronic HCV patients (HCC) (Dr . M . García Buey) . The immune response and protein expression levels of the host have been involved in the progression towards fibrosis/cirrhosis and in the development of hepatocarcinoma .
• A multicentre, three-year study including all the cases of hepatocarcinoma occurring in NASH, HCV or cryptogenic cirrhosis, called FLIP (Fatty Liver: Inhibition of the Progression) started in 2010 . The FDFT1 gene associated with the progression of the liver fibrosis in a cohort of HCV and NASH patients has been validated (Dr . M . Romero-Gómez and Dr . JA del Campo, leading the work in which 8 different Spanish hospitals have been involved)
• Dr . J . Salmeron’s group participates in the European Project “Fatty Liver: Inhibition of Progression . “Prevention and treatment of non-alcoholic fatty liver disease (NAFLD)” that started in 2010 .
• Progress has been made in the collaboration for the study of vertical mother-child HCV transmission (Dr . J . Salmeron and Dr . A . Ruíz-Extremera) .
• A collaborative line of research including three groups from our Area 2 and led by Dr . J . García- Samaniego has been consolidated, foucsing on the study of epigenetic interactions between genomic host DNA and HBV or HCV geneomes and their involvement in the progression of fibrosis and development of hepatocarcinoma (Dr . J . García-Samaniego, Dr . E . Domingo) .
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