Background/Objective: Comorbidities represent a critical risk factor in the prognosis of patients receiving immunosuppressive therapy. For patients with anti-HBc IgG positivity requiring Hepatitis B virus (HBV) prophylaxis, the long-term physiological impact of oral antivirals remains a concern. This study aims to prospectively monitor bone, renal, and metabolic dysfunctions associated with oral antiviral use and other systemic risk factors over a long-term period.

Methods: The REANT Cohort is designed as a 4-year, multicenter prospective study. The cohort will consist of patients initiated on HBV prophylaxis due to immunosuppressive treatment. Participants will undergo regular longitudinal assessments to evaluate bone mineral density, renal filtration and tubular functions, and metabolic profiles. The interplay between antiviral therapy, baseline comorbidities, and long-term organ dysfunction will be analyzed.

Conclusion: The findings from the REANT Cohort are expected to provide robust evidence regarding the safety of long-term HBV prophylaxis and assist in the development of monitoring guidelines for immunosuppressed patients with latent HBV infection.

Patient Recruitment and Enrollment:

The patient enrollment phase for the study is scheduled to conclude on June 30, 2026. Each participating center is projected to enroll 35 patients, ensuring a balanced distribution of data across the multicenter framework. The study will be initiated simultaneously across all participating sites to maintain temporal consistency in data collection.

Electronic Case Report Form (e-CRF) and Coding:

Data will be managed through a centralized e-CRF system. To ensure systematic tracking and data integrity, the system will assign a unique center code to each participating institution.

Patient Identification and Confidentiality:

For each participant, a specific patient code will be automatically generated by the system. Following the standardized protocol of the study, the patient's Full Name must be entered into the system, formatted specifically with a hyphen between the first and last name (e.g., John-Doe). This structured nomenclature will ensure uniformity in the electronic database.

Inclusion Criteria:

• Aged 18 years or older
• Positive for Anti-HBc IgG
• Must be candidate for immunosuppressive therapy.

Exclusion Criteria:

• Voluntary Withdrawal
• Failure to attend follow-up visits

The REANT Cohort is designed as a nationwide, multicenter study conducted across 14 specialized centers in Türkiye. These centers have been strategically selected to reflect a broad geographical and demographic diversity, ensuring a robust representation of the patient population receiving HBV prophylaxis.

Participating Provinces:

The study will be carried out simultaneously in the following 13 provinces (with 14 participating clinical sites):

Ankara, Sivas, İstanbul, Kocaeli, İzmir, Antalya, Adana, Gaziantep, Şanlıurfa, Diyarbakır, Samsun, Rize, Düzce

Sample Size Projection:

De-identified individual participant data collected during the trial will be made available upon reasonable request to qualified researchers for academic purposes following the publication of the primary study results.

After publication and then.

Data will be shared with qualified academic researchers who provide a methodologically sound proposal. To gain access, data requestors must sign a data use agreement (DUA) and provide proof of institutional review board (IRB) or ethics committee approval for their secondary analysis. The requested data must be used solely for the purposes of the approved research proposal.