The Oral‐Hepatic Axis: Epidemiological and Mechanistic Links Between Periodontal and Liver Diseases

ABSTRACT

Chronic liver diseases and periodontitis are prevalent inflammatory disorders that impose substantial global health and economic burdens. Increasing evidence supports an oral–hepatic axis through which periodontal dysbiosis and chronic oral inflammation may influence hepatic homeostasis and disease progression. Epidemiologic studies have linked periodontitis with metabolic dysfunction–associated steatotic liver disease (MASLD), nonalcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, and hepatocellular carcinoma. Although many associations persist after adjustment for shared risk factors, including obesity, diabetes, smoking, nutritional status, and socioeconomic factors, the independent contribution of periodontitis to liver disease remains unclear. Experimental and translational studies indicate that periodontal pathogens and their virulence factors promote systemic inflammation, endotoxemia, microbial translocation, immune dysregulation, and alterations in gut microbial ecology. Nutritional factors may further influence these interactions through their effects on host immunity, inflammation, and microbial communities. Together, these mechanisms converge along the oral–gut–liver axis to activate hepatic inflammatory, oxidative stress and profibrotic pathways that contribute to steatosis, immune activation, and fibrogenesis. Emerging evidence suggests that trained immunity, driven by metabolic and epigenetic reprogramming, may represent an additional mechanism linking periodontitis and liver disease warranting future studies. Preliminary studies indicate that periodontal therapy may reduce systemic inflammatory burden and improve hepatic biomarkers; however, evidence for an effect on liver disease progression or clinical outcomes remains limited. Similarly, hepatic dysfunction may exacerbate immune dysregulation and periodontal breakdown, reinforcing an inflammatory loop. However, overall causal relationships remain to be established. This review summarizes current epidemiological, clinical, and mechanistic evidence linking periodontitis and chronic liver diseases, highlighting the oral–gut–liver axis, shared immunometabolic and nutritional pathways. Understanding these interactions shows the significance of integrated dental‐medical care and opens new avenues for prevention and adjunctive therapy to sustain oral and hepatic health.