1. Hepatitis C. To know the real epidemiology of hepatitis C virus infection in our country. To evaluate the role of the innate immune system in the spontaneous clearance of C virus infection, as well as the evolution towards chronicity and its implication in response / failure to treatment with new direct acting antiviral agents (ADIs). Regarding the therapeutic failure, the viral variants associated with resistance will also be studied. In addition, we will study whether the hepatitis C virus is capable of producing endothelial dysfunction, subclinical atheromatosis, disorder of mineral and bone metabolism or neurocognitive manifestations and its potential reversibility after curing the infection with the new ADD agents. Finally, we intend to study whether regression occurs in liver fibrosis after the response to DDA and the pathogenic role of the enzyme Lisil-oxidase like 2 (LOXL2) in this process.
2. Molecular characterization of specific cases of human cancer. Potential implications in diagnosis and therapy. Oncogenic signaling mechanisms that control initiation, progression and response to therapy. Study from a personalized point of view, advanced cases of human cancer that at present lack effective therapies. Currently we have research projects in liver cancer as well as some types of aggressive skin cancers such as advanced melanoma, Merkel cell carcinoma and cutaneous T-cell lymphoma.
3. Fatty Liver Disease (EHDG). Obesity and insulin resistance are associated with a chronic inflammatory state. Current evidence indicates that the activation of the signal transduced at the level of the innate immune system by receptors such as TLRs and NLRs plays a decisive role in the genesis of this inflammatory state. Both receptor families, together with RLRs, make up what we know as pattern recognition receptors (PRRs). However, the role played by PRRs in the pathogenesis of HDD is largely unknown. It is possible that differences in the gene and protein expression of these peripheral, hepatic and fatty receptors between obese and non-obese subjects translate into a different susceptibility to the development of fatty liver disease.
On the other hand, the severity of the histological lesion of GHTD has been associated with the concomitant presence of hypopnea sleep apnea syndrome. The role that intermittent hypoxia plays in the development of liver injury has been studied previously. However, there are no studies aimed at evaluating the effect of hypercapnia maintained at the hepatic level. For this reason, we intend to analyze the effect of chronic hypercapnia, with or without added hypoxemia, at the liver level with ex vivo models of primary culture of immortalized hepatocytes, by analysis of gene expression associated with glucose and lipid metabolism and regulatory genes of the immune response, as well as assessing the inflammatory response induced in these cells by the infusion of lipopolysaccharide.
The partial deficiency of the lysosomal acid lipase (LAL) enzyme is an inherited, autosomal recessive pathology of lipid metabolism characterized by accumulation in lysosomes, especially in the liver of cholesterol and triglyceride esters, which may erroneously be diagnosed in the adult as HDSH. This pathology is due to mutations of the LAL gene (LIPA), of which more than 40 mutations have been described. We intend to evaluate whether the active screening by mass sequencing of the LIPA gene in adults with a diagnosis of GDHD could be relevant from a clinical point of view.
4. Alcoholic liver disease. To study the pathophysiological mechanisms of acute alcoholic hepatitis and the search for molecular targets. Analysis of the hepatic transcriptome in patients with alcoholic liver disease for the development of molecular signatures of gene expression.
5. Liver cirrhosis and portal hypertension. To characterize the natural history of hepatic cirrhosis and factors that may influence the portal pressure gradient. To evaluate the long-term role of new oral anticoagulants in the survival and development of complications of portal hypertension in patients with liver cirrhosis.
6. Liver transplantation. To study non-invasive blood biomarkers of clinical events related to liver transplantation (rejection, infection, vascular pathology, biliary disease, and short- and long-term survival of the graft).
7. Cholestatic and autoimmune liver disease. Characterize the natural history and physiopathological mechanisms of cholestatic and autoimmune liver diseases.