Fatty liver disease is the most common liver disease in the world. It affects more than a third of the adult population and 10 % of children, although most people are unaware of it. It is caused by the build-up of excess fat in the liver and is exacerbated by factors such as obesity and diabetes. It is a “silent” disease because its progression is very gradual, with most people having no symptoms and therefore being unaware of their condition. Approximately 25 % of affected individuals develop non-alcoholic steatohepatitis, which is characterised by liver inflammation and fibrosis and, if left unchecked, can lead to serious conditions such as cirrhosis or liver cancer.
Incidence of the disease has doubled since 1990 and continues to grow, to the point that experts are warning it has become an “epidemic”. It is estimated that by 2023 it will be the leading cause of liver transplants worldwide. It is directly linked to a sedentary lifestyle, alcohol consumption and a poor diet high in sugar and ultra-processed foods. The liver performs multiple functions, including filtering harmful substances, regulating hormones and storing energy and vitamins, making it one of the organs most affected by poor lifestyle choices.
Despite its very high prevalence, and unlike other non-communicable diseases with which it is closely associated such as cardiovascular disease, type 2 diabetes and obesity, fatty liver disease is under-diagnosed and remains relatively unknown by the general population. Jeffrey V. Lazarus is a researcher at ISGlobal, a centre supported by the ”la Caixa” Foundation, and leads several international initiatives to agree on a global agenda of priority actions to address the progression of the disease.
Traditionally, liver disease has been associated with alcohol consumption. The term non-alcoholic fatty liver disease was initially coined to distinguish it from alcoholic causes and was associated with being overweight or obese. However, alcoholic and non-alcoholic liver disease may share some biological processes. Many people with obesity or metabolic syndrome also consume alcohol. The traditional distinction between alcoholic and non-alcoholic fatty liver disease is not clear-cut. In addition, some experts believe that the terms non-alcoholic and fatty can be stigmatising. Therefore, an international consensus has been reached to rename the disease as metabolic hepatic steatosis, with a separate subcategory proposed for patients with higher alcohol consumption.
The disease is difficult to diagnose and no approved drug is yet available to treat it. In addition to prevention, the strategy revolves around early detection. Increasing emphasis is being placed on identifying the disease in its early stages, when there is scope for reversing fatty liver. The condition is of multifactorial origin in which several genetic and environmental factors contribute. First-degree relatives of patients with non-alcoholic fatty liver disease are at increased risk of developing it, highlighting the importance of early screening. Although some molecules that can serve as biomarkers have been identified, liver biopsy remains one of the most routine methods of diagnosis, with its main disadvantages being the invasiveness and variability of the technique.
Currently, two research projects supported by the ”la Caixa” Foundation aim to advance in the identification of non-invasive biomarkers that facilitate both the diagnosis and monitoring of disease progression and the therapeutic efficacy of treatments under development. What are they? What progress has been achieved?
Researcher Antonio Zorzano is leading a project to find biomarkers for fatty liver disease that will allow the condition to be diagnosed non-invasively. They have discovered a protein in the mitochondria of liver cells called mitofusin-2 and are investigating whether this protein can be used as a therapeutic target to design new treatments.
The team led by David Martínez Selva has identified two proteins that, in combination with a mathematical algorithm, can be used as a non-invasive biomarker to predict the onset and progression of different stages of the disease, including the most severe ones. The project is now working to advance the validation of this new biomarker, which will help identify individuals with the disease and predict its progression. It will also facilitate the development of new drugs to treat these conditions.
Speakers:
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Jeffrey V. Lazarus, head of the Health Systems Research Group at the Instituto de Salud Global de Barcelona (ISGlobal) and associate professor at the University of Barcelona.
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Antonio Zorzano, director of the Complex Metabolic Diseases and Mitochondria lab at the Institute for Research in Biomedicine (IRB Barcelona), program coordinator at CIBERDEM and full professor at the University of Barcelona.
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David Martínez Selva, main researcher of the Diabetes and Metabolism Group at the Vall d’Hebron Instituto de Investigación (VHIR).
Moderator:
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Carmen Fernández, delegate of the Health Section in Catalonia of Unidad Editorial.
Projects supported by CaixaResearch:
