MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a term that comprises a range of liver diseases (Sanyal AJ et al. (2024)). In increasing severity, these go from the excessive accumulation of fat in liver cells (liver steatosis) to liver inflammation (metabolic dysfunction-associated steatohepatitis or MASH). People who suffer from obesity and/or diabetes are at higher risk of developing MASLD (Asrani SK et al. (2019)). Worldwide, the increasing rates of obesity and diabetes have manifested in the growing prevalence of MASLD, which is the most common chronic liver disease (CLD) and the leading cause of liver-related morbidity and mortality (Marjot T et al. (2020); Chan WK et al. (2023)). This mortality is caused by associated complications, such as cirrhosis, hepatocellular cancer, and cardiovascular disease. The diagnosis of MASLD is based on the detection of steatosis, which can be done through imaging or histological techniques (Hashimoto E et al. (2013)). Liver biopsy, despite its inherent risks and costs, is still the gold standard for a definitive diagnosis. In this context, blood biomarkers that indicate fibrosis progression (akin to disease progression) can be suitable tools for the identification of MASLD, while remaining minimally invasive alternatives as opposed to liver biopsy. This is especially relevant when considering that, similarly to alcohol-related liver disease, timely lifestyle changes are crucial to the management of the disease. However, because of the asymptomatic nature of the early stages of the disease and the lack of population-wide applicability of biopsies, many patients do not seek medical attention until the damage in the liver is too severe and cannot be reversed. Once severe liver damage or cirrhosis occur, patients may experience symptoms such as accummulation of fluids in the legs or abdomen, excessive bleeding and easy bruising, jaundice, fat deposits on the skin, fatigue, and difficulty digesting fats. In this case, medications typically prescribed for other metabolic disorders, such as diabetes, can be repurposed to treat advanced liver disease (Sanyal AJ et al. (2024)). While these treatments might not provide a cure, they have the potential to decelerate or even stop the patient's decline. However, for patients with liver cirrhosis, a liver transplant can sometimes be the only option.

Differential Abundance Analysis Results

This section presents the results of the differential protein abundance analysis, visualized through a volcano plot and summarized in the accompanying table for all three comparisons: 1) disease vs. healthy samples, 2) disease vs. diseases from the same class, and 3) disease vs. all other diseases.