Background: The international consensus to revise non-alcoholic fatty liver disease to metabolic (dysfunction)-associated fatty liver disease (MAFLD) in 2020 attracted significant attention. The impact of the MAFLD definition on the research community has not been objectively assessed. We conducted an analysis of systematically collected literature on MAFLD to understand its research impact. Methods: From PubMed, Web of Science, and Scopus, the literature adopting MAFLD, written in English, and published from 2020 to 10 October 2023 was collected. The publication metrics, including publication counts, publishing journals, author countries, author keywords, and citation information, were analyzed to evaluate the research impact and key topics on MAFLD. Results: 1469 MAFLD-related papers were published in 434 journals with a steady increase in the number. The intense publishing and citations activity on MAFLD indicates the large impact of the redefinition. Topic assessment with keyword and citation analysis revealed a transition from the proposal and discussion of the redefinition to clinical characterization of MAFLD with a focus on metabolic dysfunction. Moreover, the diagnostic criteria for MAFLD showed better performance in predicting hepatic and extrahepatic outcomes compared to NAFLD. The publications were from 99 countries with evidence of strong regional and global collaboration. Multiple international societies and stakeholders have endorsed MAFLD for its utility in clinical practice, improving patient management and promoting multidisciplinary care, while alleviating stigma. Conclusion: This survey provides a quantitative measure of the considerable international impact and contributions of the MAFLD definition towards liver research and as part of the spectrum of cardiometabolic disorders.

The modern dietary exposome is calorie dense and poor in nutritional quality resulting in high prevalence of fatty liver disease and an increasing incidence of cardiometabolic disease and cancer. We investigated the impact of dietary composition on the interaction between the liver and haematopoietic systems in mice. Using xenograft and chemical-induced liver cancer models, we find that liver tumours per se have a minimal impact on haematopoietic stem and progenitor cell (HSPC) responses. In contrast, alterations in dietary composition have profound effects on the liver-bone marrow axis. Specifically, exposure to sucrose with or without dietary cholesterol has minimal impact on the HSPC response, while perturbations in bile acid biosynthesis synergises with excess dietary cholesterol to enhance HSPC responses. Pharmacological restoration of bile acid biosynthesis partially reversed these effects. We conclude that the crosstalk between liver and bone marrow, and subsequent HSPC responses is regulated by bile acid biosynthesis.

A holistic understanding of anti-tumor immunity requires examination of systemic immunity beyond the tumor microenvironment. This link between systemic and tumor immune activity is underexplored. We demonstrate that a stronger Type I interferon response in human liver tumors predicts better survival and correlates with the immune response in the adjacent non-tumor liver. Further, in patients with liver cancer, clonal hematopoiesis (CH) (a marker of systemic immune activation) is associated with a trend towards improved survival. In a mouse model of liver cancer, basal liver immune responses correlate with the degree of bone marrow hematopoietic stem and progenitor cell responses. A higher systemic and liver immune response, marked by innate myeloid cell infiltration reduces tumor burden, while sub-optimal systemic and liver immunity corresponded with a higher tumor burden. Our findings indicate that the state of bone marrow hematopoiesis impacts liver tumor outcomes, offering both therapeutic and prognostic opportunities.