References (Periodontal Disease and Liver Health: Exploring the Bidirectional Link)

Elhassan, A. T. & Peeran, S. W. The linking mechanisms between liver and periodontal diseases. EC Dent. Sci. 4, 45–54 (2016).
Liver diseases are associated with worsened periodontal health, including increased plaque, calculus, and alveolar bone loss. Evidence suggests a bidirectional relationship potentially mediated by biological mechanisms, but most studies are cross-sectional and limited by confounding factors. Further research is needed to clarify causality and underlying pathways.

Misrachi, C. Improvement in oral health in developing countries. Odontol. Chil. 38, 15–24 (1990).
Oral health improvement requires public health strategies beyond systemic fluoride use. Education programs and government-level policies are essential to reduce periodontal disease prevalence, especially in developing countries where diet, sugar intake, and cultural beliefs impact oral health.

Mutthineni, R. B., Himaja, G., Paul, R. A., Muralidharan, G., Burli, V. V. A. & Duddukuri, H. Evaluation of different local drug delivery systems in the management of chronic periodontitis: a comparative study. IP Int. J. Periodontol. Implantol. 8, 87–95 (2023).
Adjunctive local delivery of metronidazole gel or tetracycline fibers with scaling and root planing improves clinical outcomes in chronic periodontitis, reducing plaque, gingival inflammation, and pocket depth more effectively than mechanical therapy alone.

Yadav, S., Khan, G. & Mishra, B. Advances in patents related to intrapocket technology for the management of periodontitis. Recent Pat. Drug Deliv. Formul. 9, 89–98 (2015).
Intrapocket drug delivery innovations, including fibers, gels, and nanoparticles, enhance treatment efficacy for periodontitis. The development of antibiotic-free systems and novel technologies shows potential for improved localized therapy.

Graziani, F., Discepoli, N., Gennai, S., Karapetsa, D., Nisi, M., Bianchi, L., Rosema, N. A. M. & Van der Velden, U. The effect of twice daily kiwifruit consumption on periodontal and systemic conditions before and after treatment: a randomized clinical trial. J. Periodontol. 89, 345–354 (2018).
Daily kiwifruit intake reduces gingival inflammation without adjunctive periodontal treatment. No additional benefits were observed when combined with initial periodontal therapy, indicating dietary impact on gingival bleeding independent of mechanical intervention.

Hogue, C. M. & Ruiz, J. G. Oral health and aging. Springer, 1–312 (2022).
Comprehensive review of oral health in older adults, covering age-related changes, systemic disease interactions, periodontal disease management, and disparities in care access. Emphasizes prevention, health literacy, and tailored interventions for vulnerable populations.

Geisinger, M. L., Kaur, M. & Basma, H. Nonsurgical periodontal therapy: a review of current standards of care and innovations to improve gingival and periodontal health. Curr. Oral Health Rep. 6, 175–184 (2019).
Nonsurgical therapy, including patient home care and professional debridement, is effective in managing periodontitis and peri-implant disease. Adjunctive therapies may benefit high-risk patients, but long-term maintenance is crucial to prevent recurrence.

Jepsen, K. & Jepsen, S. Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis. Periodontol. 2000 71, 111–140 (2016).
Adjunctive systemic and local antimicrobials improve outcomes of nonsurgical mechanical therapy in moderate periodontitis. Benefits must be weighed against side effects and antibiotic resistance concerns.

Sweeting, L. A., Davis, K. & Cobb, C. M. Periodontal treatment protocol (PTP) for the general dental practice. J. Dent. Hyg. 82 Suppl 3, 10–18 (2008).
Structured periodontal treatment protocols in general practice improve diagnosis, treatment consistency, and patient outcomes. Emphasizes patient education, monitoring, and use of adjunctive local antimicrobials where appropriate.

Nagao, Y., Kawahigashi, Y. & Sata, M. Association of periodontal diseases and liver fibrosis in patients with HCV and/or HBV infection. Hepat. Mon. 14, 1–10 (2014).
Periodontitis is linked to progression of viral liver disease, with factors including age, obesity, brushing frequency, and platelet count affecting risk. Controlling oral disease may help prevent liver fibrosis in HCV/HBV patients.

Vijayalakshmi, R., Senthil, S., Dave, P. H., Mahendra, J., Kumari, B. N., Priya, K. L. & Namasivayam, A. Metabolomics as a diagnostic tool for periodontal diseases: an overview. IP Int. J. Periodontol. Implantol. 8, 123–131 (2023).
Metabolomics of saliva and gingival crevicular fluid offers a promising approach for early detection and understanding of periodontal disease, complementing conventional clinical assessments.

Jensen, A., Grønkjær, L. L., Holmstrup, P., Vilstrup, H. & Kilian, M. Unique subgingival microbiota associated with periodontitis in cirrhosis patients. Sci. Rep. 8, 1–10 (2018).
Cirrhosis patients with periodontitis display a unique subgingival microbiota, suggesting immune-compromised dysbiosis rather than classical periodontal pathogens as disease drivers.

Storjord, E. et al. Dental and periodontal health in acute intermittent porphyria. Life 12, 1270 (2022).
Poor dental health in AIP correlates with insulin resistance, inflammation, and kidney/liver biomarkers, indicating systemic disease influences oral outcomes.

Shin, H. S., Hong, M. H., Moon, J. Y. & Sim, S. J. Periodontal disease could be a potential risk factor for non-alcoholic fatty liver disease: an 11-year retrospective follow-up study. Clin. Oral Investig. 26, 4023–4032 (2022).
Periodontitis is associated with increased incidence of NAFLD, suggesting that prevention and management of periodontal disease may reduce liver disease risk.

Åberg, F. & Helenius-Hietala, J. Oral health and liver disease: bidirectional associations—a narrative review. Dent. J. 10, 16 (2022).
Periodontitis may contribute to liver injury through systemic inflammation and gut dysbiosis, while liver disease exacerbates oral health problems, highlighting an oral-gut-liver axis.

Wei, Ying, Deng, Yaxin, Ma, Shuting, Ran, Meixin, Jia, Yannan, Meng, Jia, Han, Fei, Gou, Jingxin, Yin, Tian, He, Haibing, Wang, Yanjiao, Zhang, Yu & Tang, Xing. Local drug delivery systems as therapeutic strategies against periodontitis: A systematic review. J. Control. Release 333, (2021).
Highlights local drug delivery systems (LDDS) as adjunctive therapy to scaling and root planing for periodontitis. LDDS offer targeted drug release, improving efficacy and reducing side effects. The review discusses bioactive agents, delivery routes, challenges, and future research directions.

Geisinger, Maria L., Geurs, Nicolaas C., Ogdon, Dorothy & Reddy, Michael S. Commentary: Targeting underlying biologic mechanisms in selecting adjunctive therapies to improve periodontal treatment in smokers. J. Periodontol. 88, 8 (2017).
Examines adjunctive therapies for smokers with periodontitis, emphasizing local antimicrobial delivery and host modulation to address disease mechanisms and improve treatment outcomes.

Sah, Abhishek K., Dewangan, Mahendra & Suresh, Preeti K. Potential of chitosan-based carrier for periodontal drug delivery. Colloids Surf. B Biointerfaces 178, (2019).
Focuses on chitosan-based carriers (fibers, films, microparticles, nanoparticles, gels) for localized sustained release in periodontal therapy. Chitosan offers antimicrobial efficacy, biodegradability, and tissue healing properties.

Varela-López, Alfonso, Bullón, Pedro, Ramírez-Tortosa, César L., Navarro-Hortal, María D., Robles-Almazán, María, Bullón, Beatriz, Cordero, Mario D., Battino, Maurizio & Quiles, José L. A diet rich in saturated fat and cholesterol aggravates the effect of bacterial lipopolysaccharide on alveolar bone loss in a rabbit model of periodontal disease. Nutrients 12, 5 (2020).
Shows that high-fat, high-cholesterol diets exacerbate LPS-induced alveolar bone loss. Poor periodontal health interacts with dietary habits to promote dyslipidemia and NAFLD progression.

KJ, Nisha. Role of Matrixmetalloproteinases in Periodontal Disease - A Review. Biomed. J. Sci. & Tech. Res. 2, 1 (2018).
Reviews the involvement of MMPs in periodontal tissue destruction and their potential as therapeutic targets. Emphasizes the need for mechanism-focused interventions to improve clinical outcomes.

Ytzhaik, Noya, Zur, Dorit, Goldstein, Chen & Almoznino, Galit. Obstructive Sleep Apnea, Metabolic Dysfunction, and Periodontitis—Machine Learning and Statistical Analyses of the DOME Big Data Study. Metabolites 13, 5 (2023).
Analyzes OSA’s association with dental and systemic conditions, identifying periodontitis as a significant risk factor. Machine learning highlights obesity, male sex, age, and periodontal disease as key predictors.

Wilensky, Asaf, Frank, Noa, Mizraji, Gabriel, Tzur, Dorit, Goldstein, Chen & Almoznino, Galit. Periodontitis and Metabolic Syndrome: Statistical and Machine Learning Analytics of a Nationwide Study. Bioengineering 10, 12 (2023).
Large-scale study linking periodontitis to metabolic syndrome components, OSA, NAFLD, and lifestyle factors. Identifies a vulnerable patient profile and emphasizes holistic risk assessment.

Yoshida, Kayo, Yoshida, Kaya, Fujiwara, Natsumi, Seyama, Mariko, Ono, Kisho, Kawai, Hotaka, Guo, Jiajie, Wang, Ziyi, Weng, Yao, Yu, Yaqiong, Uchida-Fukuhara, Yoko, Ikegame, Mika, Sasaki, Akira, Nagatsuka, Hitoshi, Kamioka, Hiroshi, Okamura, Hirohiko & Ozaki, Kazumi. Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury. Biochim. Biophys. Acta Mol. Basis Dis. 1867, 11 (2021).
Demonstrates that extracellular vesicles from Pg-infected macrophages reach distant organs, including lungs, causing inflammation and tissue injury via NF-κB activation. Provides a mechanism for systemic effects of periodontal disease.

Kaur, Kiranjit, Sculley, Dean, Wallace, Janet, Turner, Alexandria, Ferraris, Celeste, Veysey, Martin, Lucock, Mark & Beckett, Emma L.. Micronutrients and bioactive compounds in oral inflammatory diseases. J. Nutr. Intermed. Metab. 18, (2019).
Reviews the role of micronutrients in periodontal and other oral inflammatory diseases. Highlights nutritional modulation of disease progression and tissue healing through supplementation and diet.

Grønkjær, Lea Ladegaard. Periodontal disease and liver cirrhosis: A systematic review. SAGE Open Med. 3, (2015).
Systematic review showing increased prevalence of periodontal disease in cirrhosis patients. Limited evidence links oral health to disease progression and mortality, calling for further studies.

Sharma, Praveen, Cockwell, Paul, Dietrich, Thomas, Ferro, Charles, Ives, Natalie & Chapple, Iain L. C. INfluence of Successful Periodontal Intervention in REnal Disease (INSPIRED): Study protocol for a randomised controlled pilot clinical trial. Trials 18, 1 (2017).
Pilot RCT protocol investigating the effect of periodontal treatment on cardio-renal health in CKD patients. Highlights systemic inflammatory burden reduction through periodontal therapy.

Duseja, Ajay, Chahal, Gurparkash, Jain, Ashish, Mehta, Manu, Ranjan, Aditya & Grover, Vishakha. Association between nonalcoholic fatty liver disease and inflammatory periodontal disease: A case-control study. J. Indian Soc. Periodontol. 25, 1 (2021).
Finds higher prevalence of periodontal disease in NAFLD patients, with worse oral hygiene and periodontal status. Correlations noted between TNF-α and bleeding on probing, suggesting systemic inflammation links.