Cód. SSPA: IBiS-E-04
The PAIDI CTS-532 research group, part of the Medical-Surgical Unit of Digestive Diseases of the University Hospital "Virgen del Rocío", focuses its research activity on three main lines: the complications of liver cirrhosis (hepatic encephalopathy and hepatocarcinoma), hepatitis C and non-alcoholic fatty deposit disease (NAFLD).
In the facilities of the Research Unit there are two laboratory modules for experimental work, as well as eight workstations for research staff. In addition, the group has a high-security laboratory (P3) for viral transfection experiments. On the other hand, the Director of the Unit (Prof. Manuel Romero Gómez) is the principal investigator and deputy coordinator of the hepatitis area at the CIBERehd (Center for Biomedical Research in Network, liver and digestive diseases) (CIBER06/04/0047)
- Hepatic encephalopathy (HD):
The discovery of a microsatellite in the promoter area of the glutaminase gene is one of the most relevant results obtained (Ann InternMed 2010). We have also obtained important results in HD diagnostic tests (J Hepatol 2004, Hepatology 2007), also finding that they could be influenced by genetic load (last National Congress of Hepatology). The group is currently working on the hypothesis that metformin may decrease the risk of HD, having published several related papers (PLoS ONE 2012, MetBrainDis 2013), with an experimental study in rats (with porto-cava shunt to cause HD and analyze the effect of metformin) and a clinical trial in patients. As proof of the group's expertise in this field, we have written two editorials on the subject (J Hepatol 2007, Gastroenterology 2014).
Currently, the work in this project focuses on the analysis of the role of the glutamine transporter and its regulation by drugs such as metformin. The working hypothesis is based on the role of this transporter in the incorporation of glutamine and its subsequent processing by glutinase.
- Hepatitis C:
Our group has been at the forefront of hepatitis C treatment for years, participating in international clinical trials (Hepatology 2009, NEJM 2014). Currently, we are focused on the search for new therapeutic targets and the identification of genetic signals that determine the response to treatment. We have identified two proteins that play a relevant role in hepatitis C infection (PTP1B and TCTP), whose levels were altered in a cellular model of HCV infection. On the other hand, hepatitis C promotes changes in the host's lipid metabolism that determine the onset of hepatic steatosis. DGAT1 is a key enzyme in the assembly of viral particles. Quercetin can block the action of DGAT1 and also has an effect on non-structural proteins of the C virus. Finally, we have a FIS project to undertake a genome-wide association study (GWAS) with the aim of identifying genetic polymorphisms capable of predicting response to treatment and/or the occurrence of certain adverse effects during the treatment of hepatitis C.
Our group has been at the forefront of hepatitis C treatment for years, participating in international clinical trials (Hepatology 2009, NEJM 2014). Currently, we are focused on the search for new therapeutic targets and the identification of genetic signals that determine the response to treatment. We have identified two proteins that play a relevant role in hepatitis C infection (PTP1B and TCTP), whose levels were altered in a cellular model of HCV infection. On the other hand, hepatitis C promotes changes in the host's lipid metabolism that determine the onset of hepatic steatosis. DGAT1 is a key enzyme in the assembly of viral particles. Quercetin can block the action of DGAT1 and also has an effect on non-structural proteins of the C virus. Finally, we have a FIS project to undertake a genome-wide association study (GWAS) with the aim of identifying genetic polymorphisms capable of predicting response to treatment and/or the occurrence of certain adverse effects during the treatment of hepatitis C.
- Metabolic liver disease (NAFLD:
The correct differentiation between non-alcoholic steatohepatitis and simple steatosis is a key factor to achieve correct patient management, with liver biopsy being the reference diagnostic method. A tool patented by our group, DEMILI®, is a diagnostic aid based on the analysis of magnetic resonance images combining the use of optical analysis and artificial neural networks, thus forming a non-invasive technique for the diagnosis and staging of NAFLD. The Andalusian Health System-University of Seville consortium has collaborated in the development of the tool during the 7th Framework Programme of the European Commission, and the SME involved has participated in the development of similar prototypes.
Currently, the group is focused on the development of the diagnosis of metabolic liver disease by non-invasive methods (analysis of magnetic resonance images, serological markers, circulating miRNAs, etc.) that avoid the performance of a liver biopsy. Epigenetic regulation, with special emphasis on the role of miRNAs, is being analyzed in samples from patients with metabolic disease in the presence/absence of inflammation (steatohepatitis vs. simple steatosis).
