Chronic liver diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD), viral hepatitis, and alcohol-induced damage, often lead to liver fibrosis, cirrhosis, and cancer. The process of hepatic fibrogenesis involves complex interactions between liver cells and immune cells, driving inflammation and extracellular matrix deposition, which ultimately results in organ failure. Notably, metabolic adaptations within these cells, particularly in glucose and lipid metabolism, are similar to the Warburg effect seen in cancer cells. These metabolic shifts, regulated by stress responses like endoplasmic reticulum (ER) stress and autophagy, activate immune cells and hepatic stellate cells (HSCs), key players in fibrogenesis. Targeting these metabolic pathways offers potential for novel treatments to slow or reverse fibrosis progression.
Recent studies highlight the role of immunometabolism, revealing that metabolic reprogramming in liver macrophages and HSCs could be targeted for therapeutic interventions. Advances in single-cell sequencing and spatial technologies are uncovering new insights into the cellular processes and intercellular communication involved in liver fibrosis. This offers promising directions for future diagnostic and therapeutic strategies.
Reference: Horn P, Tacke F. Metabolic reprogramming in liver fibrosis. Cell Metab. 2024 Jul 2;36(7):1439-1455. doi: 10.1016/j.cmet.2024.05.003. Epub 2024 May 31. PMID: 38823393.
