Abstract
Viral hepatitis B and C (HBV and HCV) and metabolic dysfunction-associated steatotic liver disease (MASLD) are major public health concerns in Mexico, driving liver cirrhosis and hepatocellular carcinoma. The Genome-based Mexican (GENOMEX) diet, rich in bioactive compounds, may provide a nutritional strategy for preventing and managing liver disease. This study combines a literature review with integrative bioinformatic analyses to map the antiviral and hepatoprotective mechanisms activated by GENOMEX-derived bioactives and assess their therapeutic potential for preventing and managing liver disease. A literature-based review integrated with bioinformatics to identify the pathways activated by nutrients and bioactive compounds of the GENOMEX diet against HBV, HCV, and MASLD, incorporating data from in silico, in vitro, in vivo, and clinical studies, was conducted. An integrative bioinformatic approach, incorporating the Comparative Toxicogenomic Database and Functional Enrichment Analysis (STRING, DAVID, and Enrichr), was used to identify links between genes, nutrients, and bioactive compounds, with a subset of Mexican food staples included in the GENOMEX diet. The GENOMEX diet includes bioactive nutrients that may modulate molecular pathways related to immune response, oxidative stress, nutrient metabolism, and inflammation. Through integrative analysis, we identified key molecular targets-including TNF, PPARA, TP53, and IL6-that are implicated in viral replication, MASLD progression, and hepatocarcinogenesis. Functional enrichment revealed that these traditional Mexican foods and their nutrients are associated with genes and pathways involved in viral infection, metabolic dysfunction, fibrosis, and liver cancer. These findings highlight that the gene-nutrient interactions of the Mexican staple food in the GENOMEX diet can be integrated into nutritional strategies to prevent and manage HBV, HCV, and MASLD, while reducing fibrosis and HCC progression. These strategies are especially relevant in regions where antiviral treatments are limited due to high costs, antiviral resistance, and an escalating mismatch between the population's evolutionary genetics and modern environment.