Label-Free Proteomics of Severe Acute Hepatitis of Unknown Origin in Children by High-Resolution Mass Spectrometry.

Acute hepatitis of unknown etiology (non-HepA-E hepatitis) emerged affecting children in 2021 and in parallel with the COVID-19 pandemic. In the present article, we performed an analysis between two plasma samples from pediatric patients, one with non-HepA-E hepatitis and the other healthy, to evaluate possible proteomic alterations associated with viral targets as possible causative agents and pathophysiological processes using the high-resolution and label-free LC-MS/MS technique. We identified 72 altered differentially expressed proteins, 45 upregulated and 27 downregulated. Gremlin-1, a protein associated with tissue fibrosis, was detected exclusively in the positive sample. Proteins involved in immunological processes, coagulation cascade, complement cascade, lipid transport, oxidative stress, acute inflammatory response, and those related to extracellular matrix deposition were also identified. In addition, some proteins of viral origin were detected, mainly from respiratory viruses. Proteomic studies of diseases such as hepatitis and other hepatopathologies have become essential for understanding pathophysiological processes and detecting molecular triggers.