TY - JOUR
T1 - Diagnosis and Staging of Metabolic Dysfunction-Associated Steatotic Liver Disease Using Biomarker-Directed Aptamer Panels
AU - Kjær, Mikkel B.
AU - Jørgensen, Asger G.
AU - Fjelstrup, Søren
AU - Dupont, Daniel M.
AU - Bus, Claus
AU - Eriksen, Peter L.
AU - Thomsen, Karen L.
AU - Risikesan, Jeyanthini
AU - Nielsen, Søren
AU - Wernberg, Charlotte W.
AU - Lauridsen, Mette M.
AU - Bugianesi, Elisabetta
AU - Rosso, Chiara
AU - Grønbæk, Henning
AU - Kjems, Jørgen
N1 - Publisher Copyright:
© 2025 by the authors.
PY - 2025/2
Y1 - 2025/2
N2 - Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of adults globally. Despite efforts to develop non-invasive diagnostic tools, liver biopsy remains the gold standard for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and assessing fibrosis. This study investigated RNA aptamer panels, selected using APTASHAPE technology, for non-invasive MASLD diagnosis and fibrosis stratification. Aptamer panels were selected in a cohort of individuals with MASLD (development cohort, n = 77) and tested in separate cohorts: one with MASLD (test cohort, n = 57) and one assessed for bariatric surgery (bariatric cohort, n = 62). A panel distinguishing MASLD without steatohepatitis from MASH accurately stratified individuals in the development cohort (AUC = 0.83) but failed in the test and bariatric cohorts. It did, however, distinguish healthy controls from individuals with MASLD, achieving an AUC of 0.72 in the test cohort. A panel for fibrosis stratification differentiated F0 from F3–4 fibrosis in the development cohort (AUC = 0.68) but not in other cohorts. Mass spectrometry identified five plasma proteins as potential targets of the discriminative aptamers, with complement factor H suggested as a novel MASLD biomarker. In conclusion, APTASHAPE shows promise as a non-invasive tool for diagnosing and staging MASLD and identifying associated plasma biomarkers.
AB - Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of adults globally. Despite efforts to develop non-invasive diagnostic tools, liver biopsy remains the gold standard for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and assessing fibrosis. This study investigated RNA aptamer panels, selected using APTASHAPE technology, for non-invasive MASLD diagnosis and fibrosis stratification. Aptamer panels were selected in a cohort of individuals with MASLD (development cohort, n = 77) and tested in separate cohorts: one with MASLD (test cohort, n = 57) and one assessed for bariatric surgery (bariatric cohort, n = 62). A panel distinguishing MASLD without steatohepatitis from MASH accurately stratified individuals in the development cohort (AUC = 0.83) but failed in the test and bariatric cohorts. It did, however, distinguish healthy controls from individuals with MASLD, achieving an AUC of 0.72 in the test cohort. A panel for fibrosis stratification differentiated F0 from F3–4 fibrosis in the development cohort (AUC = 0.68) but not in other cohorts. Mass spectrometry identified five plasma proteins as potential targets of the discriminative aptamers, with complement factor H suggested as a novel MASLD biomarker. In conclusion, APTASHAPE shows promise as a non-invasive tool for diagnosing and staging MASLD and identifying associated plasma biomarkers.
KW - aptamer
KW - biomarker
KW - metabolic dysfunction-associated steatohepatitis
KW - metabolic dysfunction-associated steatotic liver disease
UR - http://www.scopus.com/inward/record.url?scp=85218887417&partnerID=8YFLogxK
U2 - 10.3390/biom15020255
DO - 10.3390/biom15020255
M3 - Journal article
C2 - 40001558
AN - SCOPUS:85218887417
SN - 2218-273X
VL - 15
JO - Biomolecules
JF - Biomolecules
IS - 2
M1 - 255
ER -