RESEARCH INTEREST
In recent years, our research group has focused particularly on identifying non-invasive prognostic biomarkers for the progression of chronic liver disease (CLD) to cirrhosis and hepatocellular carcinoma (HCC). HCC is the second leading cause of cancer death worldwide and has a high mortality rate because it is often diagnosed at advanced stages, when available treatments are no longer effective. Therefore, new tools are needed to improve the diagnosis and treatment of patients with HCC. Alterations in the expression of factors related to angiogenesis and fibrogenesis during the progression of CLD to HCC may provide a valuable tool for the non-invasive assessment of liver fibrosis, a key aspect in clinical decision-making. Among other clinical and demographic variables, we found that peripheral levels of angiopoietins correlated significantly with liver fibrosis in patients with chronic hepatitis C (CHC). This finding allowed us to develop a new index for the non-invasive assessment of liver fibrosis, the AngioScore, which was subsequently validated in an independent cohort of patients. In addition, our group described a significant increase in TIE2-expressing monocytes (TEMs) in the peripheral blood of patients with CHC. Monocytes, essential precursors of antigen-presenting cells, play a significant role in the pathogenesis of chronic inflammatory diseases and cancer. We proposed that the chronic expansion of TEMs—characterized by their marked proangiogenic properties and significant immunosuppressive nature—could impair an adequate immune response and promote mechanisms of liver damage. The expression of the angiopoietin receptor Tie2 on the surface of this monocyte subtype could serve as a useful marker for the non-invasive monitoring of HCC progression via a simple blood test. Furthermore, we believe that a deeper understanding of TEM regulation could lead to significant therapeutic advances. In fact, other authors have recently reported that TEMs could constitute a useful cellular biomarker for the diagnosis and prognosis of HCC. Furthermore, we have also characterized the relevance of certain genetic variants of HDACs and other angiogenic factors, receptors, and mediators in relation to the progression of fibrosis.
Therapeutic options and diagnostic procedures in hepatology have quickly advanced during the last decade, in particular, the management of viral hepatitis. Hepatitis C has become a curable disease with a sustained 99% response using direct-acting antiviral treatments.
With the increasing number of individuals with diabetes and obesity, non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent, affecting more than one-quarter of adults in the world.
In addition to liver cancer, we have other research lines:
1.- Angiogénesis y Fibrogénesis en enfermedades hepáticas crónicas.
2.- Identificación de biomarcadores de progresión de enfermedades hepáticas crónicas
3.- Monitorización de la respuesta inmunológica durante el tratamiento de la Hepatitis Crónica C con Antivirales de Acción Directa: relevancia en la aparición de complicaciones hepáticas y extrahepáticas.
4.- Caracterización en nuestro medio de las Enfermedades Hepáticas Autoinmunes: Colangitis Biliar Primaria y Hepatitis Autoinmune.
Implicación de polimorfismo genético de factores angiogénicos en la etiopatogenia de la hepatitis crónica C y su evolución a carcinoma hepatocelular. AECC. 2010-2015.
Modulación epigenética de la progresión de la hepatitis crónica C a carcinoma hepatocelular: papel de las variantes genéticas de las histonas deacetilasas. Fundación Mutua Madrileña. 2012-2015.
Estudios Inmunológicos. Proyecto Hepatitis C: Impacto del tratamiento con nuevos antivirales. CIBERehd. 2016-2017.
Rodríguez-Muñoz Y, Martín-Vílchez S, López-Rodríguez R, Hernández-Bartolomé Á, García-Buey L, Borque MJ, Moreno-Otero R, Sanz-Cameno P. Preliminary evidence of sustained expression of angiopoietin-2 during monocyte differentiation in chronic hepatitis C. Liver Int 2013. 33: 864-870. FI: 4,447(Q1). PMID: 23419030. DOI: 10.1111/liv.12125.
Poynard T, Bruix J, Schiff ER, Diago M, Berg T, Moreno-Otero R, Lyra AC, Carrilho F, Griffel LH, Boparai N, Jiang R, Burroughs M, Brass CA, Albrecht JK. Improved inflammatory activity with peginterferon alfa-2b maintenance therapy in non-cirrhotic prior non-responders: A randomized study. J Hepatol 2013. 58: 452-459. FI: 10,401(Q1). PMID: 23159770. DOI: 10.1016/j.jhep.2012.11.001.
Hernández-Bartolomé A, López-Rodríguez R, Rodríguez-Muñoz Y, Martín-Vílchez S, Borque MJ, García-Buey L, González-Moreno L, Real Y, Moreno-Otero R, Sanz-Cameno P. Angiopoietin-2 Serum Levels Improve Noninvasive Fibrosis Staging in Chronic Hepatitis C: A Fibrogenic-Angiogenic Link. PLoS One 2013. FI: 3,534(Q1). PMID: 23823085. DOI: 10.1371/journal.pone.0066143.
Martin-Vilchez, Samuel, Lara-Pezzi, Enrique, Trapero-Marugan, Maria, Moreno-Otero, Ricardo, Sanz-Cameno, Paloma. The molecular and pathophysiological implications of hepatitis B X antigen in chronic hepatitis B virus infection. Rev. Med. Virol. 2011. 21: 315-329. FI: 7,200(Q1). PMID: 21755567. DOI: 10.1002/rmv.699.
Lopez-Rodriguez, R., Trapero-Marugan, M., Borque, M. J., Roman, M., Hernandez-Bartolome, A., Rodriguez-Munoz, Y., Martin-Vilchez, S., Abad-Santos, F., Munoz de Rueda, P., Vidal-Castineira, J. R., Rodrigo, L., Salmeron, J., Moreno-Otero, R., Sanz-Cameno, P. Genetic Variants of Interferon-Stimulated Genes and IL-28B as Host Prognostic Factors of Response to Combination Treatment for Chronic Hepatitis C. Clin. Pharmacol. Ther. 2011. 90: 712-721. FI: 6,043(Q1). PMID: 21993426. DOI: 10.1038/clpt.2011.189.
