Your alcohol consumption could put your liver in danger – but this tool warns you

A whopping 25 percent of the world’s population live with fatty liver disease. While it does not necessarily affect your health, it does indeed put you in risk of developing severe liver disease such as cirrhosis.

Today, a doctor must perform a liver biopsy at a specialized clinic in a centralized health center in order to determine your individual risk. The biopsy is performed by pushing a needle through your skin and into your liver to remove a tissue sample from your liver. It is necessary yet invasive, and it is associated with complications such as bleeding.

Now, a research team led by Professor Matthias Mann at the University of Copenhagen (UCPH) has revolutionized the diagnosis tool, introducing a much more accessible method to gain potentially life-saving information about patients.

From a simple blood sample, researchers were able to predict the patient’s risk of alcohol-related liver disease, which affects six percent of the general population.

“By taking a blood sample and analyzing it, we could predict the presence of key liver pathological features and patient outcomes with performance superior or comparable to existing state-of-the-art clinical tests,” says first author Lili Niu, Postdoc at the Novo Nordisk Foundation Center for Protein Research.

No doubt this is the future. It is a fantastic screening tool, and answers everything we need to know about the patients. From a single blood test, we can measure liver fat, inflammation, and scar tissue in the liver.

Early detection is important

“Detection of different types of liver injuries is important, because it creates a better foundation for developing disease management plans for the patients. Combined with the typically silent progression of liver diseases, there is an urgent need to implement screening programs in at-risk populations for early diagnosis,” explains Lili Niu about the importance of improving current diagnostic tools for liver diseases.

Clinical Professor and Chief Physician Maja Thiele agrees.

“No doubt this is the future. It is a fantastic screening tool, and answers everything we need to know about the patients. From a single blood test, we can measure liver fat, inflammation, and scar tissue in the liver,” says Maja Thiele, who was responsible for recruiting and investigating the 659 participants for the study together with her colleagues at Odense University Hospital (OUH) and University of Southern Denmark.

The blood sample was analyzed using mass spectrometry, which is like a very advanced weight that measures molecules with extreme precision. For the professional reader, the analysis used liquid chromatography coupled online to mass spectrometry.

Published in Nature Medicine, the study is a collaborative effort with several partners in the Novo Nordisk Foundation (NNF) supported MicrobLiver research consortium, such as UCPH colleagues at the NNF Center for Metabolic Research, OUH and Max Planck Institute of Biochemistry, Germany.

New biomarkers

In the new study, the researchers were able to identify more than 300 proteins from each blood sample from the patient. This ‘list’ of proteins in the sample is called the proteome.

After identifying and measuring the proteins, they used machine learning to find proteins related to the how the specific liver disease progresses, Lili Niu explains.

“We identified three ‘panels’ of these so-called biomarkers that can detect significant fibrosis, mild inflammatory activity and any steatosis, all of which are different ways the disease can manifest itself in the tissue. In short, these biomarkers are what we are looking for in the blood sample, as they can detect any of the above-mentioned liver injuries and help predict how the disease is going to progress with the individual patient,” she says.

“In the end, it only took us two weeks of measurement time to analyze the samples from 596 individuals in the main cohort and another 63 in a validation cohort, and this throughput combined with the proteome depth is unprecedented.”

The mass spectrometer used for this study is located at the UCPH’s protein research center.

However, there is already one with the same setup as the one used for this study at Rigshospitalet, Copenhagen.

“We are interested in rolling this out as a screening tool to the general population or at-risk populations such as alcohol over-use. While we prefer to continue biomarker development with mass spectrometry-based analysis for its specificity and systematic aspect among other advantages, we want to develop other assays based on the biomarkers we have discovered,” says Professor Matthias Mann, the corresponding author who leads the Clinical Proteomics Groups at UCPH and the Max Planck Institute of Biochemistry.

“Mass spectrometry is just better”

The researchers collaborated with clinical researchers at FLASH Center for Liver Research at OUH and University of Southern Denmark. And they too are excited for the paper’s findings, explain Maja Thiele, who led the clinical studies at OUH.

“With this technology, you potentially just need a tiny blood sample taken at your general practitioner, even if you live far from a bigger city with modern hospital facilities. With the current diagnosis tool, you have to travel to a centralized and specialized clinic to get either the liver biopsy sample or advanced imaging tests,” says Maja Thiele.

Prof Thiele explains that although mass spectrometry is effective and precise, it could be years before the technique is clinically available.

“In this particular study, we compared it to the best available technologies, and mass spectrometry just seem to perform better. But it is not ‘plug and play’ just yet. We do not expect it to be implemented within the next few years,” she says.

Odense University Hospital is now setting up a new study with more participants so they can further explore the potential of the technology for liver-related disease.

You can read the full study ‘Non-invasive proteomic biomarkers for alcohol-related liver disease’ here.

Contact

Postdoc Lili Niu
+45 35 33 11 77
lili.niu@cpr.ku.dk

MD Maja Thiele
+45 21 51 30 74
maja.thiele@rsyd.dk

Press Officer Søren Thiesen
+45 28 75 29 34
s.thiesen@sund.ku.dk