Chemokines and chemokine receptors in metabolic dysfunction-associated steatohepatitis: pathogenic mechanisms and clinical implications

Metabolic dysfunction-associated steatohepatitis (MASH), an advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD), is characterized by persistent hepatic inflammation and fibrosis and frequently progresses to cirrhosis or hepatocellular carcinoma. Chemokines and their receptors, which drive disease progression and complications by orchestrating immune cell recruitment, inflammatory responses, and fibrotic processes, are central to the pathophysiology of MASH. Emerging evidence also underscores their functions as active metabolic integrators, reciprocally linking systemic insulin resistance to hepatic inflammation. This review aims to elucidate the pathogenic contributions of key chemokines such as chemokine (C–C motif) ligand (CCL)2, CCL5, CCL20, and chemokine (C–X–C motif) ligand (CXCL)10 in MASH by assessing their dual potential as therapeutic targets and non-invasive biomarkers for early detection. We also survey the current landscape of chemokine-directed therapies to critically evaluate both their efficacy and limitations. Although early clinical trials targeting chemokine pathways have yielded mixed outcomes, emerging research underscores the complexity of chemokine signaling and highlights multiple opportunities for stage-tailored and sex-specific interventions. Therefore, a deeper understanding of chemokine function in MASH holds considerable promise for facilitating the development of targeted, multidimensional treatment strategies, paving the way for personalized management of this progressive liver disorder.