Shifting the Focus

Alcohol-related liver disease (ALD) frequently leads to cirrhosis and is responsible for over half of liver-related deaths worldwide – but, despite its prevalence, there is still much to understand about the pathological features behind the disease. About 75 percent of patients with ALD remain undiagnosed until after decompensated cirrhosis has occurred, which leaves them with no good pharmaceutical treatment options. Catching ALD at the early, asymptomatic stage is the solution, but sufficiently accurate diagnostics are invasive – creating a clear need for a better understanding of the disease’s key pathophysiological features (fibrosis, inflammation, and steatosis) and, crucially, for accurate, minimally invasive biomarkers.

In search of such biomarkers, researchers used mass spectrometry (MS)-based proteomics to investigate the pathological features of ALD and the diagnostic and prognostic potential of liver and plasma proteome changes (1). Their proteome-profiling workflow demonstrated major proteome changes during ALD progression and helped them identify biomarker panels to simultaneously detect fibrosis stage ≥F2, mild inflammatory activity, and steatosis. Fibrosis was found to have the largest impact on proteome remodeling.

When benchmarked against existing tests, the biomarker panel demonstrated comparable or superior performance for detecting significant fibrosis and mild inflammatory activity. The researchers also extracted data from electronic health records to show high prognostic performance for future liver-related events and all-cause mortality.

The study provides a foundation for potential future use of routine MS-based liver disease testing, but further research must address some limitations, such as cost effectiveness for clinical practice and the need to exclude the possibility of blood contamination during correlation analysis between liver and plasma.

_{Credit: People illustrations from Shutterstock.com}