Periodontal disease is a chronic inflammatory condition associated with systemic diseases, highlighting the concept of periodontal medicine. This study aims to investigate the relationship between periodontal inflammation, oral lesions, and hepatitis B+D infection, with or without bulevirtide treatment. Oral-periodontal clinical parameters and targeted inflammatory biomarkers in saliva and gingival crevicular fluid will be evaluated in three groups: patients with hepatitis B+D receiving bulevirtide, patients with hepatitis B+D not receiving bulevirtide, and healthy controls.

Periodontal disease is characterized by chronic inflammation and destruction of tooth-supporting tissues. Emerging evidence links oral inflammatory conditions with systemic diseases, forming the basis of periodontal medicine. Hepatitis B+D infection is associated with systemic inflammation and immune dysregulation, yet little is known about its impact on oral health and inflammatory mediators in oral fluids.

This prospective, observational case-control study will recruit adult participants from the University of Medicine and Pharmacy of Craiova. Participants will be divided into three groups:

Hepatitis B+D - Bulevirtide: Patients receiving bulevirtide therapy.

Hepatitis B+D - No Bulevirtide: Patients not receiving bulevirtide.

Healthy Controls: Systemically healthy adults.

Clinical oral-periodontal examinations will be performed by a specialist periodontist, with photographs documenting oral findings. Saliva and gingival crevicular fluid will be collected using non-invasive methods to measure targeted inflammatory biomarkers. Biological samples will be analyzed at the Immunology Laboratory of the University of Medicine and Pharmacy of Craiova and at the University of Amsterdam.

Assessments will be performed at baseline and 6 months. Relevant clinical data will be extracted from medical records following data protection regulations. Statistical analysis will evaluate associations between periodontal inflammation, oral biomarkers, and hepatitis B+D status, as well as the potential impact of bulevirtide therapy.

Inclusion Criteria:

• Adults (≥18 years old) capable of providing informed consent.
• For Hepatitis B+D groups: confirmed hepatitis B and D co-infection.
• Bulevirtide group: receiving bulevirtide therapy as prescribed.
• No Bulevirtide group: not receiving bulevirtide.
• For Healthy Control group: systemically healthy adults without hepatitis B or D infection.
• Willingness to undergo oral-periodontal examination, saliva and gingival crevicular fluid collection, and oral cavity photography.

Exclusion Criteria:

• Patients with other systemic diseases that could influence periodontal health (e.g., uncontrolled diabetes, autoimmune diseases).
• Patients currently receiving other experimental therapies that may affect oral or systemic inflammation.
• Pregnancy or lactation.
• Inability or unwillingness to provide informed consent.
• History of oral or periodontal surgery within the last 6 months that could affect measurements.

The study population includes adult patients diagnosed with hepatitis B and D co-infection who are treated and followed at the Gastroenterology Clinic of the Clinical Emergency County Hospital Craiova. These patients will be divided into two cohorts based on treatment status: those receiving bulevirtide therapy as part of routine clinical care and those not receiving bulevirtide treatment.

A third cohort will consist of systemically healthy adult individuals without hepatitis B or D infection, recruited from the Periodontology Clinic of the University of Medicine and Pharmacy of Craiova, who will serve as a control group.

All participants will undergo oral-periodontal clinical examination, oral cavity documentation, and non-invasive collection of saliva and gingival crevicular fluid for the evaluation of inflammatory biomarkers. Assessments will be performed at baseline and after 6 months.