Association Between Periodontitis and NAFLD-Related Diseases: Results from the NHANES and Mendelian Randomization Study

Abstract

Background and Objectives: The purpose of this research is to utilize a combination of cross-sectional data and Mendelian randomization (MR) to establish a causal association between periodontitis and non-alcoholic fatty liver disease [NAFLD; now also referred to as metabolic associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD)], including the progression of the latter to liver fibrosis. Methods: First, a cross-sectional analysis included 4,425 participants from the National Health and Nutrition Examination Survey (NHANES) 2009 - 2014. The study employed two multivariable logistic regression models to evaluate the correlation between advanced fibrosis (AF) and periodontitis, as well as NAFLD. Model 2 controlled for age, gender, and race, while model 3 was additionally adjusted for Body Mass Index (BMI), education level, household income poverty ratio, smoking status, physical activity, and history of diabetes. Second, in the two-sample MR analysis, periodontitis (n = 17,353 cases) was used as the exposure, and NAFLD (n = 2,275 cases), fibrosis (n = 146 cases), cirrhosis (n = 1,142 cases), and fibrosis/cirrhosis (n = 1,841 cases) were used as outcomes, and causality validation was performed. Sensitivity analyses, such as heterogeneity tests, multiple validity tests, and exclusion analyses, were also conducted to ensure the reliability of the findings. Results: Both the cross-sectional and MR analyses yielded null results. In the observational study, including participants (mean age: 53.1 years, 50.3% male), there was no significant correlation between periodontitis and NAFLD or AF. Similarly, MR analyses found no significant association between genetically predicted periodontitis and liver conditions. Conclusions: According to cross-sectional research, there is no discernible link between NAFLD or liver fibrosis and periodontal disease, and MR analyses do not support a causal relationship between them.