NEW YORK – A set of blood protein markers may help identify obese individuals with a liver condition called "metabolic-associated steatotic liver disease" (MASLD) who are at risk of progressing to a more advanced inflammatory stage of disease, known as "metabolic-associated steatohepatitis" (MASH), according to a new study.
"Our investigations detail the evolution of liver-secreted and plasma proteins with MASLD progression, providing a rich resource defining human liver-secreted proteins and creating a predictive model to stratify patients with obesity at risk of MASH," senior and corresponding author Matthew Watt, a researcher at the University of Melbourne, and his colleagues wrote in a study published in Cell Reports Medicine on Thursday.
For their study, he and his colleagues used liquid chromatography-tandem mass spectrometry to profile proteins present in blood plasma and liver biopsy samples from 160 bariatric patients who were classified as obese and had MASLD diagnoses ranging from relatively moderate to severe. Participants included 85 with MASL, 33 MASH cases, and 42 with no liver pathology.
"We focused on MASH given it is the more severe form of MASLD and is associated with accelerated progression of hepatic fibrosis and development of [hepatocellular carcinoma]," the authors wrote.
"Despite the high prevalence of MASLD, there remains a lack of practical, effective, and noninvasive screening options to identify early-stage disease before progression to cirrhosis, particularly in obese patients," they explained, noting that the "current gold standard for MASLD and MASH diagnosis is liver biopsy with histopathology."
By tallying proteins in samples from different forms of liver disease, the team was able to track down MASH-related changes in liver protein secretion, along with corresponding shifts in blood plasma proteins and biological processes.
The researchers identified 54 proteins linked to MASH histological features, along with three dozen liver-secreted proteins with ties to MASH. Their proteomic analyses did not pick up significant blood or liver-secreted proteome changes in individuals with MASL compared to liver disease-free control individuals.
With these data, the team focused in on six blood plasma biomarkers for potentially stratifying patients according to their MASH risk, independent of liver fibrosis: APOF, PCSK9, AFM, S100A6, HbA1c percentage, and AZGP1. These markers were then assembled into a so-called "APASHA" model that was subsequently validated in another 106 participants receiving bariatric surgery.
The blood-based APASHA model was able to identify MASH with 77 percent accuracy in the validation cohort, which included 24 individuals with MASH, 52 MASLD cases, and 30 participants with no liver pathology.
"External validation of these targets in other cohorts and development into antibody-based approaches have the potential for the APASHA model to assist healthcare providers to identify patients at risk of MASH who require additional care," the authors wrote.