A new method can diagnose alcohol-related liver disease and provide a prognosis. A researcher says that the results of a major study may be useful in identifying drug targets for liver disease.
Many people drink too much alcohol. This can lead to alcohol-related liver disease, which, at its most severe, can damage the liver so much that lifelong dialysis or a liver transplant is required.
New research shows how a blood test can diagnose the various stages of alcohol-related liver disease, thereby providing opportunities for timely intervention and treatment.
The same study also identified the proteins that are up- and downregulated in the development of alcohol-related liver disease, and these may become therapeutic targets.
“Our study may be important not only for diagnosing people with alcohol-related liver disease but also for developing drugs for treatment,” explains a researcher behind the study, Lili Niu, a Postdoctoral Fellow from the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen.
The research, which was led by Matthias Mann, Professor and Head of Research at the Novo Nordisk Foundation Center for Protein Research, has been published in Nature Medicine. The MicrobLiver consortium also collaborated on the research.
Plasma and liver tissue samples from 659 people
A clinical research team under Aleksander Krag at Odense University Hospital in Denmark acquired plasma and liver tissue samples from 659 people, some of whom had various stages of alcohol-related liver disease.
Lili Niu is investigating methods to identify the protein content of liver cells, and she used the samples to create a protein landscape for each test participant using various advanced technologies.
A protein landscape describes the condition of the liver, including disease.
Part of the research involved optimising the mass spectrometry–based proteomics analysis methods.
“Over the years, our group has developed better methods for using mass spectrometry to map proteomes in clinical studies. In this study, we optimised the methods to quantify as many proteins from our samples as possible, since we needed optimal data quality,” says Lili Niu.
Three pathological features of alcohol-related liver disease
After carrying out protein landscaping, the researchers looked for characteristics that could be used to distinguish between controls and individuals with a key pathological feature of alcohol-related liver disease: fatty liver, inflammation or fibrosis, whose end stage is referred as cirrhosis.
Fatty liver is the first stage of alcohol-related liver disease, and cirrhosis occurs just before the liver fails.
Lili Niu says that she identified biomarkers that indicate the stage of disease for each person.
The researchers also identified the signalling pathways that are up- or downregulated in the liver at various stages of alcohol-related liver disease.
“This is inherently interesting, since we can identify many signalling pathways that may be relevant for therapeutic targeting,” explains Lili Niu.
46 proteins dysregulated in both plasma and the liver
The researchers also profiled the proteome of the plasma samples and integrated data from the liver tissue samples and the plasma samples to identify signals in a plasma sample that reflect changes in the liver.
They found 46 proteins that were dysregulated in both plasma and liver tissue samples, and these can be used to diagnose the various stages of alcohol-related liver disease.
The researchers selected three biomarker panels of dysregulated proteins in plasma that indicated whether the individuals had alcohol-related liver disease with fatty liver, inflammation or fibrosis (and cirrhosis). Many of these proteins were also dysregulated in the liver.
“We compared biomarker panels with the best existing tests and found that our method was at least as good at diagnosis, if not better. In addition, current tests can only identify up to two pathological features of the disease, but we can identify all three,” says Lili Niu.
Large-scale trials are underway
In addition to being able to diagnose the three stages of alcohol-related liver disease, the researchers also made prognoses based on their analysis.
The researchers followed the participants for 5 years and observed how the disease had progressed.
Their biomarkers were not only accurate in identifying the degree of liver disease but also predicted how the subjects were doing subsequently.
“As technology improves, our results will improve even more. We are interested in further validating our findings in larger cohorts, such as the cohort of 20,000 people our partners are following,” explains Lili Niu, who adds that the method can probably also be used to diagnose other organ diseases by using a blood test.