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08 March 2023

Lipid analysis of alcohol-related liver disease offers potential new therapeutic targets

Analyses of lipids identified differences between normal liver samples and liver samples from patients with alcohol-related liver disease. The information could be used to find new treatments and for earlier detection of the disease.

liver cells microscope 780x450

Alcohol-related liver disease (ALDs) is prevalent, with one in five people that misuse alcohol found to have exhibited liver fibrosis – damaged and scarred liver tissue and a marker of advanced ALDs such as cirrhosis. Alcohol is a leading cause of cirrhosis with half of worldwide deaths from cirrhosis being caused by alcohol.

ALD is characterised by severe liver damage that causes swelling, weight loss, drowsiness and vomiting blood. The number of people with ALD in the UK has risen in the last few decades as alcohol misuse has increased.

It is widely understood that excessive alcohol consumption affects liver function and the transport of lipids. But researchers and clinicians currently don’t understand the molecular development of alcohol-related liver diseases, particularly its early development.

New research analysed the lipids produced in patients with early-onset ALD. As part of a multi-institute team, Dr Cristina Legido-Quigley from the Institute of Pharmaceutical Science and the Steno Diabetes Centre, Copenhagen led experiments using mass-spectrometry lipidomics. This is an analysis of lipids within cells of the body that measures and identifies the types of molecules within samples.

A total 315 patients with ALD had paired liver and blood samples analysed and compared to 51 control blood samples. The results, published in Gastroenterology, identified 18 different classes of lipids within hundreds of types of total lipids that were different in liver samples of patients with ALD.

The most notable class of lipids were sphingomyelins. Researchers found less sphingomyelins in scarred samples of liver tissue which is a major symptom of liver damage from ALD.

The paper determined that the lower level of lipids throughout the body occurred in the early development of ALD. Not only does this elucidate some of the molecular mechanism during its development, but it also confirms new potential therapeutic targets for ALD.

This unique alcohol-related liver disease cohort with progressive fibrosis allowed us to profile lipids and use modern data science to reveal a new potential therapeutic target. This is important because once the disease progresses to late stage, there are no treatments.

Dr Cristina Legido-Quigley, Senior Lecturer in the Institute of Pharmaceutical Science

Further research suggested that the reduction of sphingomyelins was solely a characteristic of ALD. Patients with other liver disorders like concomitant metabolic syndrome and non-alcoholic fatty liver disease were found to not have a reduced level of sphingomyelins. This suggests that their reduction could potentially be used as a biomarker exclusively to detect ALD.

Additionally, being able to provide earlier diagnoses would be beneficial as ALD is currently diagnosed at a late stage where symptoms are more severe, and the liver’s regenerative ability is compromised.

In this story

Cristina Legido-Quigley

Senior Lecturer in Systems Medicine