Abstract
BACKGROUND: Vibrational and chiroptical spectroscopy of blood plasma is an advanced experimental diagnostic approach that allows the identification of disease-specific molecular patterns. This study aimed to test its potential to distinguish between different stages of metabolic dysfunction-associated steatotic liver disease (MASLD) including liver fibrosis. METHODS: We analyzed blood plasma samples from 29 patients with metabolic dysfunction-associated steatohepatitis (MASH) and 24 MASLD patients with simple steatosis using Fourier-transform infrared (FTIR) spectroscopy, Raman spectroscopy and electronic circular dichroism (ECD) spectroscopy to distinguish: (i) MASH; (ii) MASH with moderate to advanced fibrosis; and (iii) overall fibrosis. RESULTS: FTIR spectroscopy distinguished MASH from simple steatosis with a sensitivity of 73% and a specificity of 92%, with an area under the receiver operating characteristic curve (AUROC) of 0.92, p < 0.001. In addition, FTIR spectroscopy identified MASH with moderate to advanced fibrosis (F2-3) from MASH/steatosis with no to mild fibrosis (F0-1) with a sensitivity of 87% and specificity of 78% (AUROC 0.91, p < 0.001). Furthermore, regardless of the MASH/steatosis diagnosis, fibrosis (F1-3) was distinguished from F0 by the combination of data from the three spectroscopic methods with a sensitivity of 79% and a specificity of 88% (AUROC 0.91, p < 0.001). Both FTIR and Raman spectroscopy alone discriminated all target groups with an AUROC > 0.82. CONCLUSIONS: This pilot study revealed the potential of blood plasma spectroscopy to identify and differentiate patients with various stages of MASLD.