Liver Diseases

Group leader: Jesús María Bañales, M.D., Ph.D.

Biodonostia HRI. Ikerbasque Research Fellow. jesus.banales@biodonostia.org

Strategic Objectives

The liver is the largest organ in the human body, and one of the most important organs at a physiopathological level. It is made up of two types of epithelial cells: hepatocytes and cholangiocytes. Hepatocytes represent 70-80% of the total mass of the liver, and they play a part in fundamental physiological processes, such as drug detoxification, the synthesis of cholesterol and bile salts, and the generation of primary bile. Cholangiocytes are the cells that make up the bile ducts and they modulate the composition and flow of the bile generated in the canaliculi of the hepatocytes. Although the cholangiocytes only represent 3-5% of the total population of cells in the liver, they participate in the generation of up to 30% of the total bile flow, inducing its alkalinisation and fluidification.

The liver can be directly or indirectly affected by a range of diseases called hepatopathies, and which represent the fifth leading cause of death worldwide. Among these hepatopathies are those of viral origin [hepatitis C (HCV) and B (HBV)], alcoholic origin (ALD), non-alcoholic fat (NAFLD), genetic (polycystic liver disease and haemochromatosis) and autoimmune (autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis). When these hepatopathies become chronic, they can lead to the development of cirrhosis and/or liver cancer, e.g. hepatocellular carcinoma (HCC) and/or cholangiocarcinoma (CCA).

One of the great commitments of our Research Group is to boost research inspired by patients’ needs, driving new and innovative work channels, in order to quickly and efficiently transfer the scientific advances to those channels to help prevent and cure these diseases. This is our set objective, and we have several lines of research aimed at this purpose.

Main lines of research

  • Fibrosis, Cirrhosis and Hepatocarcinoma: Chronic liver damage is a pathology that is characterised by a progressive increase in hepatic fibrosis that can lead to more advanced stages of the disease, such as cirrhosis, and ultimately, liver cancer or hepatocarcinoma. This disease, affecting millions of people around the world, has a very varied etiology (e.g. fatty diet, virus, autoimmunity, drugs, alcohol, mutations, epigenetic alterations, etc.).
    • Study both on in vitro and in vivo models of the molecular mechanisms involved in the appearance and development of chronic liver damage, and the search for new therapeutic tools for their prevention and/or treatment.
    • Clinical studies to improve the treatment of chronic hepatitis C.
    • Assessment of different non-invasive tests as methods for diagnosing and monitoring hepatic fibrosis (e.g. magnetic resonance).
  • Cholangiocarcinoma: Cholangiocarcinomas (CCAs) are tumours that originate in the bile duct. Their incidence is rising around the world and their therapeutic options are very limited due to their late diagnosis and high chemoresistance. The etiology of CCA is unknown. However, chronic biliary inflammation and high levels of bile acids appear to play a key role in the development of this cancer.
    • Study of the molecular mechanisms involved in the appearance and development of this type of tumour, as well as in the clarification of the causes of its high level of chemoresistance.
    • Search for new therapeutic strategies.
  • Alcoholic hepatopathy: It is estimated that between 2% and 16% of the Spanish population are excessive consumers of alcohol, which is responsible for approximately 12,000 deaths in Spain every year, representing 4.5% of total mortality. Biological, cultural, social and genetic factors have been described that predispose a person to the development of alcoholism or to the risk of consuming excessive alcohol.
    • Studies for the line of genetic polymorphisms and environmental factors associated with excessive alcohol consumption, which would enable their incidence to be prevented.
  •  Non-alcoholic steatosis: It is also known as fatty liver disease, and is characterised by the intrahepatocytic accumulation of fatty acids, which can lead to more aggressive pathological conditions, such as steatohepatitis and/or hepatocarcinoma. Its prevalence in developed countries ranges between 3% and 24% of the population. Among the factors that encourage its development are obesity and diabetes.
    • Determination of the molecular mechanisms involved in the appearance and development of this pathology, using in vitro and in vivo models, as well as the search for new therapies for its treatment.
    • Development of new non-invasive methods for the quantification of intrahepatic fat in patients (e.g. magnetic resonance), which enables a better diagnosis and monitoring of the disease.
  •  Iron overload: Hereditary haemochromatosis is the most common form of iron overload. Its diagnosis has improved since Feder et al. isolated the HFE gene in 1996 and discovered the mutations related to the disease. However, many patients have proved to have negative genetic studies, and consequently require diagnostic confirmation by quantifying the concentration of iron in their liver (LIC), which has traditionally been accomplished by liver biopsy.
    • Development and assessment of the validity of non-invasive techniques (magnetic resonance) to diagnose iron overload and monitor its treatment.
    • Study of new genes associated with iron overload.

Team Members

Name Surname Center E-mail
Edurne Almandoz Cortajarena Donostialdea IHO edurne.almandoz@biodonostia.org
Jose María Alustiza Echeberria OSATEK jmalustiza@osatek.es
Ander Arbelaiz Cosio Biodonostia HRI ander.arbelaiz@biodonostia.org
Juan Ignacio Arenas Ruíz Tapiador Donostialdea IHO juanignacio.arenasruiztapiador@osakidetza.eus
Adolfo Beguiristain Gómez Donostialdea IHO adolfo.beguiristaingomez@osakidetza.eus
Javier Caballero Camino Biodonostia HRI
Agustin Castiella Eguzkiza Bajo Deba IHO agustin.castiellaeguzkiza@osakidetza.eus
Mª Dolores De Juan Echavarri Donostialdea IHO mdolores.dejuanechavarri@osakidetza.eus
Oihane Erice Azparren Biodonostia HRI oihane.erice@biodonostia.org
Aitor Esparza Baquer Biodonostia HRI aitor.esparza@biodonostia.org
Raúl Jiménez Agüero Donostialdea IHO raul.jimenezaguero@osakidetza.eus
Ibone Labiano Ciriza Biodonostia HRI ibone.labiano@biodonostia.org
Adelaida Lacasta Muñoa Donostialdea IHO adelaida.lacastamunoa@osakidetza.eus
Ainhoa Lapitz Dambolenea Biodonostia HRI ainhoa.lapitz@biodonostia.org
Pui Yuen Lee Biodonostia HRI puiyuen.lee@biodonostia.org
Paula Olaizola Rebe Biodonostia HRI paula.olaizola@biodonostia.org
Maria Jesús Perugorria Montiel Biodonostia HRI matxus.perugorria@biodonostia.org
Inmaculada Ruíz Montesinos Donostialdea IHO inmaculada.ruizmontesinos@osakidetza.eus
Maria Emma Salvador Pardo OSATEK esalvador@osatek.net
Álvaro Santos Laso Biodonostia HRI alvaro.santos@biodonostia.org
Eva Zapata Morcillo Bajo Deba IHO evamaria.zapatamorcillo@osakidetza.eus

Scientific Output

Originals

Publicados: 10 / 57

COLONPREV Study Investigators, Spanish Gastroenterological Assoc. Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening.

Quintero E, Castells A, Bujanda L, Cubiella J, Salas D, Lanas A, Andreu M, Carballo F, Morillas JD, Hernández, C, Jover R, Montalvo I, Arenas J, Laredo E, Hernández V, Iglesias F, Cid E, Zubizarreta R, Sala T, Ponce M, Andres M, Teruel G, Peris A, Roncales MP, Polo-Tomas M, Bessa X, Ferrer-Armengou O, Grau J, Serradesanferm A, Ono A, Cruzado J, Perez-Riquelme F, Alonso-Abreu I, De la Vega-Prieto M, Reyes-Melian, JM, Cacho G, Diaz-Tasende J, Herreros-de-Tejada A, Poves C, Santander C, Gonzalez-Navarro A.

N. Engl. J. Med. 2012; 366: 697-706. FI: 53.298 (Q1).

Correlation between RECIST-conventional imaging techniques, morphologic response by CT and histopathologic response, in hepatic metastasis secondary to colorectal cancer: The AVAMET study.

Vera R, Gomez ML, Ayuso JR, Figueras J, Garcia P, Martinez-Marin V, La Casta A, Ruiz A, Safont MJ, Aparicio J, Campos JM, Camara JC, Martin-Richard M, Montagut C, Pericay C, Vieitez de Prado JM, Falco E, Jorge M, Marin M, Salgado M, GEMCAD.

J. Clin. Oncol. 2015; 33. FI: 18.428 (Q1).

Use of Hy’s law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury.

Robles-Diaz M, Lucena MI, Kaplowitz N, Stephens C, Medina-Cáliz I, González-Jimenez A, Ulzurrun E, Gonzalez AF, Fernandez MC, Romero-Gómez M, Jimenez-Perez M, Bruguera M, Prieto M, Bessone F, Hernandez N, Arrese M, Andrade RJ.

Gastroenterology. 2014; 147: 109-118. FI: 13.926 (Q1).

Inhibition of metalloprotease hyperactivity in cystic cholangiocytes halts the development of polycystic liver diseases.

Urribarri AD, Munoz-Garrido P, Perugorria MJ, Erice O, Merino-Azpitarte M, Arbelaiz A, Lozano E, Hijona E, Jimenez-Agueero R, Fernandez-Barrena MG, Jimeno JP, Marzioni M, Marin JJG, Masyuk TV, LaRusso NF, Prieto J, Bujanda L, Banales JM.

Gut. 2014; 63: 1658-1667. FI: 13.319 (Q1).

Expression of SLC22A1 Variants May Affect the Response of Hepatocellular Carcinoma and Cholangiocarcinoma to Sorafenib.

Herraez E, Lozano E, Macias RIR, Vaquero J, Bujanda L, Banales JM, Marin JJG, Briz O.

Hepatology. 2013; 58: 1065-1073. FI: 12.003 (Q1).

Pasireotide Is More Effective than Octreotide in Reducing Hepatorenal Cystogenesis in Rodents with Polycystic Kidney and Liver Diseases.

Masyuk TV, Radtke BN, Stroope AJ, Banales JM, Gradilone SA, Huang B, Masyuk AI, Hogan MC, Torres VE, LaRusso NF.

Hepatology. 2013; 58: 409-421. FI: 12.003 (Q1).

Tumor progression locus 2/Cot is required for activation of extracellular regulated kinase in liver injury and toll-like receptorinduced TIMP-1 gene transcription in hepatic stellate cells in mice.

Perugorria MJ, Murphy LB, Fullard N, Chakraborty JB, Vyrla D, Wilson CL, Oakley F, Mann J, Mann DA.

Hepatology. 2013; 57: 1238-1249. FI: 12.003 (Q1).

Inhibition of Cdc25A Suppresses Hepato-renal Cystogenesis in Rodent Models of Polycystic Kidney and Liver Disease.

Masyuk TV, Radtke BN, Stroope AJ, Bañales JM, Masyuk AI, Gradilone SA, Gajdos G, Bedekovicsne CN, Bakeberg JL, Ward CJ, Ritman EL, Kiyokawa H, LaRusso, NF.

Gastroenterology. 2012; 142: 622-310. FI: 11.675 (Q1).

Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation.

Perugorria MJ, Wilson CL, Zeybel M, Walsh M, Amin S, Robinson S, White SA, Burt AD, Oakley F, Tsukamoto H, Mann DA, Mann J.

Hepatology. 2012; 56: 1129-1139. FI: 11.665 (Q1).

Up-regulation of microRNA 506 leads to decreased Cl-/HCO3- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis.

Bañales JM, Sáez E, Uriz M, Sarvide S, Urribarri AD, Splinter P, Tietz Bogert PS, Bujanda L, Prieto J, Medina JF, LaRusso NF.

Hepatology. 2012; 56: 687-697. FI: 11.665 (Q1).

Reviews

Publicados: 3 / 3

Polycystic liver diseases: advanced insights into the molecular mechanisms.

Perugorria MJ, Masyuk TV, Marin JJ, Marzioni M, Bujanda L, LaRusso NF, Banales JM.

NAT REV GASTRO HEPAT. 2014; 11: 750-761. FI: 10.807 (Q1).

MicroRNAs and cholestatic liver diseases.

Marin JJG, Bujanda L, Banales JM.

Curr. Opin. Gastroenterol. 2014; 30: 303-309. FI: 3.664 (Q1).

Pancreatic metastases due to renal carcinoma. Our cases and a literature review.

Markinez I, Jimenez R, Ruiz I, Villarreal E, Lizarazu A, Borda N, Arteaga X, Medrano MA, Guisasola E, Beguiristain A, Enriquez-Navascues JM.

Cir. Espan. 2013; 91: 90-95. FI: 0.871 (Q3).

Editorials

Publicados: 3 / 3

Osseous metaplasia in a gastric adenomatous polyp

Zapata E, Castiella A, Zubiaurre L, Agirre A, Rodríguez J.

Endoscopy. 2012; 44: 81-0. FI: 5.210 (Q1).

Representacion Grp HEBRA. Screening practices for hepatitis B virus prior to viral reactivation risk therapies among different medical specialties.

García-Bengoechea M, Hernández-López C, Crespo J, Gea F.

HEBRA Project. Med. Clin. 2012; 139: 498-501. FI: 1.385 (Q2).

Autologous cephalic duodenopancreatectomy with superior mesenteric vein dissection and reconstruction using the renal vein.

Markinez I, Ruiz I, Arteaga X, Medrano MA, Beguiristain A.

Cir. Espan. 2013; 91: 269-271. FI: 0.871 (Q3).

Letters

Publicados: 8 / 8

Porphyria cutanea tarda in the Basque Country: significance of HFE gene mutations and of external factors.

Castiella A, Zapata E, Otazua P, Zubiaurre L.

Liver Int. 2012; 32: 1597-0. FI: 3.824 (Q1).

Mild hepatic iron overload in dysmetabolic hyperferritinemia: MRI may overestimate the liver iron concentration values.

Castiella A, Alustiza JM, Zapata E, Emparanza JI, Otazua P, Zubiaurre L, Aguirre A.

Ann. Hematol. 2012; 91: 961-0. FI: 2.615 (Q2).

Somatic second-hit mutations leads to polycystic liver diseases.

Banales JM, Munoz-Garrido P, Bujanda L.

World J. Gastroenterol. 2013; 19: 141-143. FI: 2.547 (Q2).

Iron Overload and HFE Mutations: Are They Relevant in Cryptogenic Cirrhosis?

Castiella A.

Hepat. Mon. 2012; 12: 126-127. FI: 2.190 (Q3).

Is the role of liver biopsy changing in hemochromatosis? A non invasive approach is ready.

Castiella A, Alustiza JM, Zapata E, Otazua P, Fernández J, Zubiaurre L.

Gastrointest. Liver Dis. 2012; 21: 326-327. FI: 1.811 (Q3).

Low disphagia as a form of presentation of a cyst of duplication of cardia.

Aranburu I, Castielle A, Zapata E, Izaguirre E, Elorza JL, Zubiaurre L, Iribarren A, Asensio JI, Larburu S.

Rev. Esp. Enferm. Dig. 2015; 107: 464-465. FI: 1.414 (Q4).

Gallbladder metastasis from renal cell carcinoma, an extremely rare neoplastic dissemination location.

Zevallos JC, Lizarazu A, Guisasola E, Medrano MA, Jimenez R.

Cir. Espan. 2014; 92: 295-296. FI: 0.890 (Q3).

Toxic hepatocellular hepatitis due to labetalol.

Castiella A, Iglesias U, Zapata E, Zubiaurre L, Iribarren A.

Gastroenterol. Hepatol. 2015; 38: 326-327. FI: 0.838 (Q4).

Others

Publicados: 2 / 2

Is MRI becoming the new gold standard for diagnosing iron overload in hemochromatosis and other liver iron disorders?.

Castiella A, Alustiza JM, Zapata E, Emparanza JI.

Imaging Med. 2013; 5: 515-524. FI: 0.000 (Q0).

Medición del T2* hepático y cardíaco en la hemocromatosis secundaria.

Barrera MC, Uranga M, Sánchez J, Alústiza JM, Gervás C, Guisasola A.

Radiologia. 2013; 55: 331-339. FI: 0.000 (Q0).

Projects

Projects 6 / 6

Papel de los exosomas en el desarrollo y patogenia de las Colangitis Esclerosante Primaria (CEP): Nueva estrategia diagnóstica y pronóstica.

Investigador Principal: Jesús María Bañales Asurmendi. Entidad Financiadora: ISCIII Instituto de Salud Carlos III. Año inicio: 2014. Año final: 2017.

Papel del receptor TREM-2 en el desarrollo y progresión del daño hepático crónico: Nueva diana terapéutica. TREM2.

Investigador Principal: María Jesús Perugorria Montiel. Entidad Financiadora: Gobierno Vasco, Departamento de Desarrollo Económico y Competitividad. Año inicio: 2013. Año final: 2014.

Papel del receptor TREM-2 en el desarrollo y progresión del daño hepático crónico y la Hepatocarcionogénesis: Nueva diana terapéutica.

Investigador Principal: María Jesús Perugorria Montiel. Entidad Financiadora: ISCIII Instituto de Salud Carlos III. Año inicio: 2014. Año final: 2017.

Papel de FXR y TGR5 en la Fisiopatología del Colangiocarcinoma: Nueva estrategia terapéutica. BACCA.

Investigador Principal: Jesús María Bañales Asurmendi. Entidad Financiadora: Gobierno Vasco, Departamento de Desarrollo Económico y Competitividad. Año inicio: 2013. Año final: 2014.

Ácido Ursodesoxicolico: Nueva estrategia para el tratamiento de las Enfermedades Hepáticas Poliquísticas.

Investigador Principal: Jesús María Bañales Asurmendi. Entidad Financiadora: ISCIII Instituto de Salud Carlos III. Año inicio: 2013. Año final: 2015.

Estudio en Fase III, multicéntrico, aleatorizado, doble ciego, de grupos paralelos para comparar la eficacia y seguridad de Sorafenib más Pravastatina frente a Sorafenib más placebo en pacientes con Hepatocarcinoma avanzado.

Investigador Principal: Juan Ignacio Arenas Ruiz Tapiador. Entidad Financiadora: Gobierno de España, Ministerio de Sanidad, Servicios Sociales e Igualdad. Año inicio: 201a. Año final: 2015.

Patents

Este grupo no tiene Patents