Advanced liver fibrosis can eventually stop the liver from performing its various functions in the human body, as scarred tissue displaces organ tissue. The possible consequence: organ failure. A study by Tamar Mchedlidze and Dr. Stefan Wirtz, Department of Medicine 1 (Head: Prof. Dr. Markus F. Neurath) at Universitätsklinikum Erlangen, FAU, has proven for the first time that interleukin 33 – a cytokine in the immune system – can contribute to causing liver fibrosis. Medicinal treatment which targets this molecule could potentially protect patients from this feared disease. The researchers recently published their findings in the journal Immunity.*
Chronic liver diseases are among the leading causes of death in the USA and the number of patients with diseased livers in Germany is increasing. Most patients die of cirrhosis which is the final stage of liver fibrosis: this disease occurs as a consequence of chronic liver diseases and cannot be cured at the moment. Liver fibrosis causes harmful deposits of connective tissue to form in the liver, which eventually cause liver failure.
FAU researcher Stefan Wirtz explains the challenge of liver fibrosis: ‘At the moment treatment options for severe liver fibrosis are extremely restricted – the disease cannot be cured.’ ‘Now we have managed to identify an immunological factor which contributes to causing this disease for the first time, which opens up promising methods for treatment or even prevention.’
Previous investigations have assumed that liver fibrosis is caused by an abnormal immune response from the liver, but until now medical research has not been able to discover much about the molecules and cells which are part of the disease. Stefan Wirtz and his team were able to prove that interleukin 33 levels in the blood of patients with liver diseases is much higher than in control groups. Based on this observation, the researchers used pre-clinical models to investigate whether injections of interleukin 33 lead to increased deposits of ECM proteins in the liver and were able to confirm their hypothesis. Genetic modifications which led to the absence of interleukin 33 protected the models from the disease for the most part. The researchers also confirmed that interleukin 33 activates ILC2 immune cells, which had not been previously associated with liver disease.
‘Interleukin 33 may become a new biomarker for identifying patients at an early stage of liver fibrosis,’ explains Stefan Wirtz. ‘This could help patients make lifestyle decisions that may stop the disease advancing any further.’ The most important implication of the research according to Wirtz is that medication could be developed which targets Interleukin 33 or ILC2 immune cells to cure fibrosis and chronic liver diseases.
Dr. Stefan Wirtz
Phone: +49 (0)9131 85 35882