Microplastics and Liver Health: A PRISMA Systematic Review of Hepatic Injury Mechanisms and Carcinogenic Potential

Objective: Microplastics (MPs) and nanoplastics (NPs) are increasingly detected in water, food, air and, importantly, within human tissues. Because the liver receives both intestinal and systemic inputs, it becomes a likely site where these particles may accumulate or exert secondary effects. Experimental work suggests hepatotoxicity mediated through oxidative, inflammatory and metabolic pathways, but the strength, direction and clinical relevance of these changes remain uncertain. To perform a PRISMA-compliant systematic review of in vivo and translational studies examining how MPs influence hepatic structure and function, with emphasis on mechanisms related to oxidative stress, inflammation, gut–liver axis disturbance, metabolic dysregulation, fibrotic signaling and carcinogenesis. A specific goal was to determine whether MPs can initiate hepatocellular carcinoma (HCC). Methods: A structured search of PubMed/MEDLINE, Scopus, and Web of Science (2016–2026) identified experimental in vivo, ex vivo, and translational human biomonitoring studies reporting hepatic outcomes after MP or NP exposure, using Boolean combinations of microplastic/nanoplastic and hepatic/hepatotoxicity terms. Two independent reviewers screened titles, abstracts, and full texts against predefined eligibility criteria. Studies lacking liver-related biological endpoints were excluded. Risk of bias was assessed using an adapted SYRCLE tool (animal studies) and a qualitative methodological evaluation (in vitro studies). Data were extracted for polymer type, exposure route, and mechanistic endpoints, then synthesised narratively across seven mechanistic domains. 22 studies met predefined criteria and are summarised in three analytic tables. Results: Across mammalian models and aquatic vertebrates, MPs consistently induced hepatic oxidative stress, mitochondrial injury, Kupffer-cell activation, inflammatory signaling, barrier disruption along the gut–liver axis, and metabolic changes resembling early MASLD. Some studies reported fibrotic signaling and stellate-cell activation, though these findings were less frequent. No study showed de novo tumor initiation by MPs; however, a limited number of studies suggest mechanistic plausibility for a tumor-promoting role under conditions of combined hepatic stress rather than independent carcinogenic activity. Conclusions: Current evidence suggests that MPs disturb hepatic metabolic and immune homeostasis through interconnected oxidative, mitochondrial and gut-derived pathways. These effects echo mechanisms that drive MASLD progression and could potentially worsen underlying liver disease. However, there is no evidence that MPs independently initiate HCC, highlighting a major gap in the field. Studies using long-term, low-dose and environmentally relevant exposures are needed to define the true clinical impact of MPs on liver health. In addition, current animal models primarily focus on healthy livers, but mechanistic parallels between MP-induced injury and established pathways in viral hepatitis (HBV/HCV), autoimmune hepatitis, alcohol-associated liver disease, and MASLD suggest that microplastic exposure could potentially worsen pre-existing hepatic susceptibility. No studies have directly evaluated these interactions. However, the overlap in oxidative stress, immune activation, mitochondrial dysfunction, and gut-derived endotoxemia increases concern that MPs may quicken decompensation or progression in chronic liver diseases.