Low molecular weight (LMW) thiols, particularly glutathione, play pathogenic roles in various multiorgan diseases. The liver is central for the production and systemic distribution of LMW thiols; thus, it is particularly susceptible to the imbalance of redox status that may determine increased oxidative stress and trigger the liver damage observed in metabolic dysfunction-associated steatotic liver disease (MASLD) models and humans. Indeed, increased LMW thiols at the cellular and extracellular levels may be associated with the severity of MASLD. Here, we present a systematic literature review of recent studies assessing the levels of LMW thiols in MASLD in in vivo and in vitro models and human subjects. Based on the PRISMA 2020 criteria, a search was conducted using PubMed and Scopus by applying inclusion/exclusion filters. The initial search returned 1012 documents, from which 165 eligible studies were selected, further described, and qualitatively analysed. Of these studies, most focused on animal and cellular models, while a minority used human fluids. The analysis of these studies revealed heterogeneity in the methods of sample processing and measurement of LMW thiol levels, which hinder cut-off values for diagnostic use. Standardisation of the analysis and measure of LMW thiol is necessary to facilitate future studies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic progressive hepatopathy in children, and the identification of non-invasive biomarkers is urgently needed. Growth differentiation factor 15 (GDF15) was associated with MASLD in adults. In this study, we investigated the circulating and hepatic levels of GDF15 and their association with liver damage in pediatric MASLD and in a murine model. This observational study included 158 children with biopsy-proven MASLD. Patients with MASLD were categorized into two groups based on steatohepatitis (MASH) presence and evaluated for GDF15 circulating levels, while GDF15 hepatic levels were assessed only in a subset of patients. Children with MASLD exhibited higher levels of circulating GDF15 compared to the controls. Moreover, the MASH subgroup had significantly higher values of GDF15 compared to the Not-MASH subgroup. The GDF15 levels in the MASH subgroup showed a positive correlation with fibrosis. Finally, the hepatic expression of the GDF15 gene correlated with GDF15 circulating levels and with the hepatic expression of the COL1A1 and COL3A1 genes in 15 children with MASLD. In conclusion, our study demonstrated that GDF15 levels are associated with liver damage, reinforcing the potential role of GDF15 as a biomarker for MASLD-related fibrosis in children.