Non-alcoholic fatty liver disease (NAFLD) is the most common type of liver disease and the hepatic component of the metabolic syndrome. It is estimated to affect 17-33% of the adult U.S. population depending on race/ethnicity and diagnostic modality. Known risk factors are insulin resistance and obesity while proinflammatory state is increasingly recognized as an emerging risk factor. Though, the pathogenesis of NAFLD is poorly understood, epidemiologic studies have linked proinflammatory cytokines to certain components of the metabolic syndrome and NAFLD. Thus, factors known to elicit a systemic inflammatory response potentially represent an unrecognized but modifiable pathway in NAFLD etiopathogenesis. Specifically, chronic periodontitis (CP), a major cause of tooth loss, affects approximately 45% of the adult U.S. population and is reported to exacerbate insulin resistance. Additionally, animal and epidemiologic studies have reported the propensity for CP to elicit low-grade systemic inflammation via proinflammatory cytokines. The hypothesized molecular mechanism linking elevated cytokine levels to NAFLD has been demonstrated in experimental animal and epidemiologic studies. CP was recently linked to NAFLD in humans but the study was insufficiently powered. Due to uncertainty in prevalence of NAFLD and limited knowledge regarding its relation with CP, we propose to address this gap in literature through a secondary data analysis of data from the Study of Health in Pomerania (SHIP), a population based prospective cohort study of northeastern Germany. SHIP study is a well-characterized cohort of 4,308 participants who experience high levels of abdominal obesity, metabolic syndrome, and other cardio-metabolic risk factors. Replication analysis will be conducted using data from the Hispanic Community Health Study/Study of Latinos in which n=14,000 adults had measurements of serum transaminases and clinical periodontal status. Relationships between CP and NAFLD will be investigated cross-sectionally in both cohorts and longitudinally in SHIP. In both cohorts, comparable protocols were used to measure of periodontal pocket depth and clinical attachment level. NAFLD was characterized using serum transaminase levels in both cohorts and with hepatic ultrasound at baseline and follow-up in SHIP. Estrogens are reported to exert protective effects against NAFLD occurrence among premenopausal because of its antioxidant effects, thus we hypothesize a gender difference in the proposed CP/NAFLD association. Lastly, because of the inflammatory basis of CP and NAFLD, we further propose to assess modification of the CP/NAFLD association by a panel of genetic markers of inflammation.
The causes of non-alcoholic fatty liver disease (NAFLD) are unclear, despite it being the most common form of liver disease, with the best evidence implicating systemic inflammatory response to low-grade infections. This epidemiologic study will investigate the contribution of periodontal disease and its systemic-inflammatory consequences to NAFLD through secondary analysis of data from the Study of Health in Pomerania (SHIP), with replication using data from the Hispanic Community Health Study / Study of Latinos (HCHS/SoL). Phenotypic data from oral examination, liver ultrasound, and serum enzymes together with targeted genotypes will be analyzed from both cohorts to determine if periodontitis represents a risk factor for components of the metabolic syndrome and for expression of NAFLD.
| Akinkugbe, Aderonke A; Barritt, A Sidney; Cai, Jianwen et al. (2018) Periodontitis and prevalence of elevated aminotransferases in the Hispanic Community Health Study/Study of Latinos. J Periodontol 89:949-958 |
| Akinkugbe, A A; Avery, C L; Barritt, A S et al. (2017) Do Genetic Markers of Inflammation Modify the Relationship between Periodontitis and Nonalcoholic Fatty Liver Disease? Findings from the SHIP Study. J Dent Res 96:1392-1399 |
| Akinkugbe, Aderonke A; Slade, Gary D; Barritt, A Sidney et al. (2017) Periodontitis and Non-alcoholic Fatty Liver Disease, a population-based cohort investigation in the Study of Health in Pomerania. J Clin Periodontol 44:1077-1087 |
