A promising new approach to treating potentially deadly liver disease
An experimental new treatment is showing early promise in the fight against liver fibrosis – a serious and often silent condition that affects around 2 million people in the UK.
Liver fibrosis happens when the liver becomes damaged – often due to long-term issues like alcohol use, obesity or chronic infections – and starts to develop scar tissue. Over time, that scarring can get worse and lead to serious complications such as liver failure or cancer.
The problem is that most people don't know they have it until the damage is advanced. And there are no approved drugs to stop or reverse the scarring process.
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In a recent study, my colleagues and I found that blocking an enzyme called HDAC6 with new drugs could help reduce liver scarring in people with liver fibrosis.
This discovery could form the basis of future treatments and offer hope for those living with chronic liver conditions.
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Fibrosis occurs when the liver responds to injury by producing too much of the material that normally helps repair tissue, known as the 'extracellular matrix'. Over time, this repair process can become unbalanced, leading to a buildup of scar tissue.
A key part of this process involves hepatic stellate cells. When the liver is injured, these normally inactive cells become activated and turn into scar-producing cells that drive fibrosis.
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HDAC6 helps control how cells respond to stress and inflammation and how they move and organise themselves. Our recent research suggests it also plays an important role in turning on the liver cells that cause scarring after injury. That's why we're exploring HDAC6 as a potential target for new treatments that could help prevent or even reverse liver fibrosis.
In our lab, we developed two new drugs specifically designed to block HDAC6 activity.
Liver slices
To see if these compounds could be useful as treatments, we tested them on precision-cut slices of human liver tissue at Newcastle University. This model keeps the liver's natural 3D structure and mix of cells, making it a valuable way to study how diseases develop and how drugs might work.
Our results were striking. Treating the liver slices with HDAC6 inhibitors greatly reduced signs of fibrosis, showing that these compounds can stop – and possibly even reverse – the scarring process at the cellular level.
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The inhibitors showed very little toxicity, suggesting they could be safe for further development.
This research is a step forward in finding a treatment for liver fibrosis. Unlike previous treatments that targeted broad mechanisms or caused side-effects, our HDAC6 inhibitors provide a more targeted approach. By focusing on a key cause of fibrosis, we may be able to stop the disease before it reaches irreversible stages.
The implications are enormous. Liver disease is responsible for around 4% of premature deaths globally, and the burden is rising in line with alcohol misuse, obesity, and the use of multiple medications (known as 'polypharmacy'). A targeted therapy that interrupts fibrosis at its root could change the lives of tens of thousands of patients annually – not only in the UK but around the world.
While these early findings are encouraging, more work is needed before HDAC6 inhibitors can be tested in humans.
Our next steps include refining the experimental drugs, testing their effects in lab animals, and looking at how they might work alongside existing treatments.
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As researchers and healthcare professionals seek new ways to tackle chronic diseases, targeted approaches like this one could redefine how we treat conditions once considered untreatable. For patients with liver fibrosis, this new knowledge could mean a longer, healthier life for millions of people with liver fibrosis.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
Maria Teresa Borrello does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
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