Microplastics and nanoplastics: Emerging drivers of hepatic pathogenesis and metabolic dysfunction

Advanced liver disease, including cirrhosis and hepatocellular carcinoma (HCC), represents a major global health challenge, driven in part by the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). In parallel, micro-and nanoplastics (MNPs) have emerged as pervasive environmental contaminants with potential hepatotoxic effects. This review provides an in-depth analysis of current knowledge regarding the role of MNPs in the pathogenesis of cirrhosis and HCC, particularly in the context of the growing MASLD burden, and identifies key areas for future research. The literature search included original studies and review articles indexed in PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar from January 1, 2014, to November 1, 2024. Evidence from animal models indicates that MNP exposure may induce hepatic changes resembling those seen in human MASLD and metabolic dysfunction-associated steatohepatitis (MASH) through both direct and indirect mechanisms. Importantly, MNPs may act as a "second hit" in the presence of pre-existing metabolic stress, potentially exacerbating liver injury. However, human data remain scarce, with only two small-scale studies investigating MNPs in clinical cohorts. Recent advances in analytical methods for quantifying MNPs in blood present new opportunities to explore their association with MASLD, cirrhosis, and HCC in human populations. While significant progress has been made in understanding MNP-induced hepatotoxicity in experimental models, their clinical relevance to human liver disease progression remains largely unexplored. Further multidisciplinary research integrating environmental science, molecular biology, and clinical hepatology is urgently needed.