Inflammatory response in liver disease
GROUP INFORMATION
For the past few years, our research group has been particularly focused on identifying non-invasive prognostic biomarkers of chronic liver disease (CLD) progression to cirrhosis and hepatocellular carcinoma (HCC).
HCC is the second leading cause of cancer death in the world and has a high mortality rate when diagnosed only in advanced stages, in which the available treatments are no longer effective. New tools are therefore required to improve diagnosis and treatment of patients with HCC.
The altered expression of angiogenic and fibrogenic factors during the course of CLD to HCC could provide a key clinical decision-making tool for non-invasive assessment of hepatic fibrosis. Among other clinical and demographic variables, we found that peripheral levels of angiopoietins correlated significantly with hepatic fibrosis in patients with chronic hepatitis C (HCC). These findings allowed us to develop an index for the non-invasive evaluation of hepatic fibrosis, AngioScore, which was extensively validated in an independent patient series.
Our group also described a significant increase in Tie2-expressing monocytes (TEMs) in the peripheral blood of patients with HCC. Monocytes, essential precursors of antigen-presenting cells, contribute significantly to the pathogenesis of chronic inflammatory diseases and cancer. We proposed that the chronic expansion of TEMs, which are characterised by their marked pro-angiogenic properties and their remarkable immunosuppressive nature, could prevent an appropriate immune response and promote mechanisms that cause liver damage. The expression of the angiopoietin receptor Tie2 on the surface of this monocyte subtype could serve as a useful marker for non-invasive monitoring, in a simple blood test, of CLD progression. In addition, we believe that a deeper understanding of EMT regulation may lead to important therapeutic advances. Interestingly, meanwhile, other authors described how EMTs could function as useful molecular and cellular diagnostic biomarkers for HCC.
Furthermore, we have also characterised the significance of certain genetic variables of HDACs and other angiogenic factors, receptors and mediators, in relation to fibrosis progression.
Based on this evidence, our group is currently focused on addressing the role of all the above factors, humoral, cellular and genetic as liquid biopsy for diagnosis, prognosis and monitoring of progression from CLD to HCC.
The H Index of the group’s main researcher, Dr Luisa Consuelo García Buey, is 28.
Lines of Research.
The group pursues four main lines of research.
1.- Angiogenesis and fibrogenesis in chronic liver disease.
2.- Identifying biomarkers of chronic liver disease progression.
3.- Monitoring immune response during Chronic Hepatitis C treatment with Direct Action Antivirals: relevance in the appearance of hepatic and extrahepatic complications.
4.- Characterising Autoimmune Liver Diseases in our environment: Primary Biliary Cholangitis and Autoimmune Hepatitis.
Team members
Group leader: Luisa Consuelo García Buey Hospital Universitario La Princesa |
Other team members:
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Sanz Cameno, María Paloma. 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.
García Buey, Luisa Consuelo. 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.
