Kjær Mikkel B, Jørgensen Asger G, Fjelstrup Søren, Dupont Daniel M, Bus Claus, Eriksen Peter L, Thomsen Karen L, Risikesan Jeyanthini, Nielsen Søren, Wernberg Charlotte W, Lauridsen Mette M, Bugianesi Elisabetta, Rosso Chiara, Grønbæk Henning, Kjems Jørgen
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.
Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.
Biomolecules. 2025 Feb 10;15(2):255. doi: 10.3390/biom15020255.
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, 77) and tested in separate cohorts: one with MASLD (test cohort, 57) and one assessed for bariatric surgery (, 62). A panel distinguishing MASLD without steatohepatitis from MASH accurately stratified individuals in the developmentcohort (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.
代谢功能障碍相关脂肪性肝病（MASLD）影响着全球三分之一的成年人。尽管人们努力开发非侵入性诊断工具，但肝活检仍然是诊断代谢功能障碍相关脂肪性肝炎（MASH）和评估纤维化的金标准。本研究调查了使用APTASHAPE技术选择的RNA适配体组，用于MASLD的非侵入性诊断和纤维化分层。在一组患有MASLD的个体（开发队列，77例）中选择适配体组，并在单独的队列中进行测试：一个是患有MASLD的队列（测试队列，57例），另一个是接受减肥手术评估的队列（62例）。一个能够区分无脂肪性肝炎的MASLD和MASH的适配体组在开发队列中准确地对个体进行了分层（AUC = 0.83），但在测试队列和减肥手术队列中失败了。然而，它确实能够区分健康对照和患有MASLD的个体，在测试队列中AUC达到0.72。一个用于纤维化分层的适配体组在开发队列中能够区分F0和F3 - 4纤维化（AUC = 0.68），但在其他队列中则不能。质谱分析确定了五种血浆蛋白为鉴别性适配体的潜在靶点，补体因子H被认为是一种新的MASLD生物标志物。总之，APTASHAPE作为一种用于诊断和分期MASLD以及识别相关血浆生物标志物的非侵入性工具显示出了前景。
