Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), now the most common cause of chronic liver disease, is estimated to affect around 30% of the global population. In MASLD, chronic liver injury can result in scarring or fibrosis, with the degree of fibrosis being the best-known predictor of adverse clinical outcomes. Hence, there is huge interest in developing new therapies to inhibit or reverse fibrosis in MASLD. However, this has been challenging to achieve, as the biology of fibrosis and candidate antifibrotic therapeutic targets have remained poorly described in patient samples. In recent years, the advent of single-cell and spatial omics approaches that can be applied to human samples have started to transform our understanding of fibrosis biology in MASLD. In this Review, we describe these technological advances and discuss the new insights such studies have provided, focusing on the role of epithelial cell plasticity, mesenchymal cell activation, scar-associated macrophage accumulation, and inflammatory cell stimulation as regulators of liver fibrosis. We also consider how omics techniques can enhance our understanding of evolving concepts in the field, such as hot versus cold fibrosis and the mechanisms of liver fibrosis regression. Finally, we touch on future developments and how they are likely to inform a more mechanistic understanding about how fibrosis might differ between patients and how this could influence optimal therapeutic approaches.