Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease) is a leading cause of chronic liver disease worldwide. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH, formerly known as non-alcoholic steatohepatitis) with subsequent liver cirrhosis and hepatocellular carcinoma formation. The advent of current technologies such as single-cell and single-nuclei RNA sequencing have transformed our understanding of the liver in homeostasis and disease. The next frontier is contextualizing this single-cell information in its native spatial orientation. This understanding will markedly accelerate discovery science in hepatology, resulting in a further step-change in our knowledge of liver biology and pathobiology. In this Review, we discuss up-to-date knowledge of MASLD development and progression and how the burgeoning field of spatial genomics is driving exciting new developments in our understanding of human liver disease pathogenesis and therapeutic target identification.

代谢功能障碍相关脂肪性肝病 （MASLD，以前称为非酒精性脂肪性肝病） 是全球慢性肝病的主要原因。MASLD 可进展为代谢功能障碍相关脂肪性肝炎 （MASH，以前称为非酒精性脂肪性肝炎），随后出现肝硬化和肝细胞癌形成。当前技术的出现，如单细胞和单核 RNA 测序，改变了我们对肝脏稳态和疾病的理解。下一个前沿领域是将这些单细胞信息置于其原生空间方向的上下文中。这种理解将显着加速肝病学的发现科学，从而导致我们对肝脏生物学和病理生物学的知识进一步发生重大变化。在这篇综述中，我们讨论了 MASLD 发展和进展的最新知识，以及新兴的空间基因组学领域如何推动我们对人类肝病发病机制和治疗靶点识别的理解取得令人兴奋的新发展。