Pathogenesis of metabolic dysfunction-associated steatotic liver disease and donor liver damage

作者：Chuheng Gou, Wenjie Zhang, Hao Xu, H. Zhang, Rui Ding, Xuan Zhang · 发表于：iLiver · 年份：2025 · DOI：10.1016/j.iliver.2025.100195 · 被引用次数：12 · 研究领域：Liver Disease Diagnosis and Treatment

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than a quarter of adults worldwide. MASLD is associated with severe medical burdens and leads to further reduction of the donor pool for liver transplantation. However, there is a lack of systematic evaluation of the pathogenesis of MASLD development and MASLD graft damage. As a multisystem disorder, the pathogenesis of MASLD is closely related to genetics, metabolic and endocrine disorders, imbalanced intestinal flora, abnormal hepatocyte homeostasis, and hepatic inflammation. Mutations or single nucleotide polymorphisms and epigenetic modifications in multiple genes increase a person's susceptibility to developing MASLD. Lipid accumulation is a central pathogenic driver, and intestinal microbiota and endocrine disorders can exacerbate steatosis and inflammation. These issues cause endoplasmic reticulum stress in hepatocytes, leading to apoptosis and promoting the recruitment and activation of immune cells. Ultimately, hepatic stellate cells are activated, resulting in liver fibrosis. These molecular and pathological changes are important causes of why a MASLD donor liver is likely to suffer ischemia-reperfusion injury and cold ischemic injury. Lipid deposition, microcirculation disturbance, and inflammation in the MASLD donor liver exacerbates ischemia-reperfusion-related damage. During transplantation, cold ischemia time should be minimized, and machine perfusion implemented and treatments for MA...