Proteomics-based Blood Test May Replace Biopsy for Diagnosis of Liver Disease

A mass spectroscopy-based proteomics assay was able to predict whether an individual subject was afflicted by alcohol-related liver disease and whether the individual was at risk of disease progression.

Alcohol-related liver disease (ALD) is a common chronic liver disorder, which affects nearly 25% of the world's population and frequently progresses to cirrhosis. With rising incidence rates, ALD has become the leading cause for liver transplantation and is responsible for more than half of all liver-related deaths. ALD progresses through a range of histological lesions, starting with alcohol-related fatty liver, to subclinical steatohepatitis featuring hepatic inflammation, which drives progressive fibrosis ultimately leading to cirrhosis.

Currently an invasive liver biopsy is the preferred method for detecting ALD despite the risk of complications such as bleeding and infection. Since approximately 75% of patients with ALD are diagnosed only after cirrhosis has occurred, making them ineligible for optimal drug treatment, detection of ALD at an early, asymptomatic stage could provide opportunities for slowing or preventing disease progression.

Searching for a non-invasive approach for diagnosis of ALD, investigators at the Max Planck Institute of Biochemistry (Munich, Germany) and the Novo Nordisk Foundation Center for Protein Research (Hellerup, Denmark) explored the diagnostic and prognostic capability of plasma proteomics in 596 individuals (137 controls and 459 individuals with ALD), 360 of whom had biopsy-based histological assessment.

The investigators analyzed all plasma samples and 79 liver biopsies using a mass spectrometry (MS)-based proteomics workflow with short gradient times and an enhanced, data-independent acquisition scheme in only three weeks of measurement time.

Results of the analyses revealed that in plasma and liver biopsy tissues, metabolic functions were downregulated whereas fibrosis-associated signaling and immune responses were upregulated. Machine learning models identified proteomics biomarker panels that detected significant fibrosis and mild inflammation more accurately than existing clinical assays. These biomarker panels were found to be accurate in prediction of future liver-related events and all-cause mortality.

Senior author Dr. Matthias Mann, director of the proteomics and signal transduction group at the Max Planck Institute of Biochemistry, said, "We are interested in rolling this out as a screening tool for the general population or at-risk populations, such as alcohol over-users, for early detection of liver diseases. We will continue biomarker development with mass spectrometry-based analysis for its specificity and systematic aspects, among other advantages. Further, we want to develop other assays for other diseases as well."

The ALD study was published in the June 2, 2022, online edition of the journal Nature Medicine.

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