Natalie Day
Chief Executive Officer, the Foundation for Liver Research
Dr Shilpa Chokshi
Acting Director and Chief Scientific Officer, the Institute of Hepatology, London
The human body is built to repair itself and the most astonishing example of this is the liver, which is the only solid organ to regenerate. New research is helping us better understand liver disease.
The liver is an organ designed to meet the daily challenges of keeping us healthy. Yet increasingly, as is evident from the astonishing 400% rise in rates of liver disease in the UK over the last 40 years, we are pushing it beyond the limits of tolerance.
Unlocking the reasons for different clinical outcomes
Alcohol is one of the most well-known challenges testing the liver. Addressing the underlying psychological addiction and achieving abstinence remain the main treatments for alcoholic liver disease (ALD).
There are no targeted treatment options for the underlying physical disease. Interestingly, not all people who drink at harmful levels develop liver disease. Understanding the precise mechanisms that confer protection in some individuals might be key to unlocking the development of effective and targeted therapies for others.
The World Health Organization (WHO) identifies alcohol as the third largest risk factor for ill-health in developed countries, behind tobacco and high blood pressure. Historically there has been very limited investment in research despite the significant global heath burden.
Stigma associated with alcohol abuse is one possible reason. Yet diabetes and obesity, both closely related to lifestyle choices and behaviours, have received considerably more research attention and resources.
Research-led solutions
Another reason is the lack of good experimental models mimicking the development of disease. The complexity of alcohol related liver injury, in terms of early damage and processes leading to fibrosis and cirrhosis, cannot be replicated in isolated cells, cell lines and small animal models.
It is research that opens the way to better patient survival.
This research problem has hampered the development of prognostic and diagnostic biomarkers. Pre-clinical testing of therapeutic targets developed with these models has shown they do not reliably translate into effective treatments in humans.
A game-changing technique
A new research technique may represent an answer. The human precision cut liver slice model takes ultrathin liver slices (around 00−250 µm thick) which more accurately simulate the intracellular mechanisms and complex architecture of the liver.
Used in research in ALD, it is enabling examination of the hepatotoxic response to alcohol and when slices are cultured in combination with immune cells, allows re-creation of interactions between the immune system and the normal/diseased liver. This is potentially game-changing, as many patients who develop alcohol-related cirrhosis die of bacterial infections which overwhelm their impaired immune systems.
This is just one example of innovative, research-led thinking transforming how we treat patients with liver disease. It is research that opens the way to better patient survival.
References:
[1] Palma, E., Doornebal, E. & Chokshi, S. Precision-cut liver slices: a versatile tool to advance liver research. Hepatol Int 13, 51–57 (2019). https://doi.org/10.1007/s12072-018-9913-7
[2] Chokshi, S. Alcoholic liver disease: why research is vital. Health and Social Care News. November 19, 2018. https://www.openaccessgovernment.org/alcoholic-liver-disease-research-vital/32373/
