CRITICAL MEDIATORS OF INFLAMMATION-DRIVEN HEPATOCARCINOGENESIS INDUCED BY METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE

Introduction and Objectives

Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly recognized as a precursor to hepatocellular carcinoma (HCC). In addition, sustained inflammation is emerging as a critical promoter of the transition from steatosis to liver cancer. To evaluate the role of inflammation in hepatocarcinogenesis induction by MASLD.

Materials and Methods

Fischer 344 rats were fed a diet rich in fat, cholesterol, and sucrose, and administered low doses of CCl₄ and DEN intraperitoneally for 16 weeks. Liver damage, steatosis, inflammatory, and carcinogenesis-related markers were assessed through biochemical assays, immunohistochemical, and western blot analysis. Data were analyzed using one-way analysis with significance set at p < 0.05. All the experiments were approved by the ethics committee of CINVESTAV-IPN (protocol No. 310-20).

Results

The liver of MASLD-HCC groups shows visible tumor nodules and surface alterations (Figure 1A). Immunohistochemical and immunofluorescence analysis revealed a marked increase in NLRP3, GSDMD, and GSTP1 levels in MASLD-HCC group (Figure 1B-D), indicating the activation of inflammasome and pyroptosis pathways and suggesting a link between chronic inflammation and cellular transformation. The hepatotoxins induced a strong inflammatory response, with increased hepatic expression of NLRP3 inflammasome components. These alterations were accompanied by the increase in serum liver damage and neoplastic markers, which correlated with the appearance of neoplastic lesions.

Conclusions

Chronic inflammation induced by diet and hepatotoxic compounds serves as a central driver in the HCC development-associated MASLD. This finding supports the hypothesis that the inflammation-carcinogenesis axis plays a significant role in MASLD progression.