Extracellular vesicles and circulating biomarkers in liver disease: from pathophysiology to clinical outcomes
Extracellular vesicles and circulating biomarkers in liver disease: from pathophysiology to clinical outcomes
Chronic liver diseases represent a major global health burden, with disease progression driven by complex interactions between inflammation, fibrosis, metabolic dysfunction, and systemic complications. This thesis of Yakun Li aimed to advance the understanding of liver disease pathophysiology and identify circulating biomarkers with diagnostic, prognostic, and translational potential, focusing on extracellular vesicles (EVs) and metabolic alterations.
The first part investigated the role of EVs in liver disease. EVs were explored as carriers of antioxidant enzymes and mediators of intercellular communication, highlighting their potential in regulating oxidative stress and inflammatory responses. The contribution of bacterial EVs to gut–liver axis interactions and their therapeutic implications was further discussed. In addition, plasma EV-associated proteins were evaluated as potential biomarkers for disease stratification in metabolic dysfunction-associated steatotic liver disease (MASLD). The effects of geniposidic acid on hepatic stellate cell activation provided further insights into mechanisms underlying liver fibrosis.
The second part focused on circulating biomarkers in advanced liver disease and liver transplantation. Plasma GlycA, branched-chain amino acids, and citrate were investigated in relation to mortality, metabolic complications, and physical function. These studies demonstrated that circulating biomarkers reflect systemic inflammation, metabolic dysregulation, and disease-related alterations beyond conventional clinical parameters.
Collectively, this thesis provides novel insights into EV-mediated mechanisms and circulating biomarkers across the liver disease continuum, supporting improved disease stratification, prognostication, and future translational applications.