Group leader: Jesús María Bañales, Ph.D.

Biodonostia HRI. Ikerbasque Research Professor. 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.