Systematic review links periodontitis to NAFLD progression and HCC risk

Oral microbiota plays a critical role in linking oral and systemic health, with dysbiosis closely associated with the onset and progression of chronic liver diseases. This review systematically examines the central role of the “oral–gut–liver axis” in hepatic pathophysiology. Epidemiological evidence has identified periodontitis and specific oral pathogens, such as Fusobacterium nucleatum (F. nucleatum), as independent risk factors for the progression of non-alcoholic fatty liver disease (NAFLD), development of cirrhosis, and incidence of hepatocellular carcinoma (HCC). The underlying mechanisms primarily involve four interrelated pathways: (1) direct bacterial translocation, where pathogens such as F. nucleatum colonize the liver via bacteremia and activate oncogenic pathways; (2) systemic dissemination of bacterial metabolites, such as lipopolysaccharides (LPS), driving hepatic inflammation, oxidative stress, and fibrosis via Toll-like receptor 4 (TLR4) signaling and reactive oxygen species (ROS)-mediated pathways; (3) systemic immune inflammation, wherein periodontitis acts as a chronic inflammatory focus that continuously releases pro-inflammatory mediators into the circulation; and (4) indirect effects mediated by gut microbiota dysbiosis, whereby oral bacteria compromise the intestinal barrier, facilitating the influx of gut-derived toxins into the liver. These findings underscore the significant impact of oral health on hepatic status. In the short term, oral microbial profiles represent promising noninvasive diagnostic and prognostic biomarkers. Preliminary clinical trials indicate that periodontal therapy can improve metabolic parameters in patients with NAFLD. In the long term, promoting interdisciplinary collaboration between hepatology and oral medicine and strategically integrating oral health interventions into the comprehensive management framework for liver diseases hold significant public health potential for mitigating the global burden of hepatic disorders.