Hepatitis B reactivation with TNF-α inhibitors: assessing antiviral prophylaxis efficacy - protocol for systematic review and meta-analysis.

BACKGROUND

The widespread use of TNF-α inhibitors (infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept) in gastrointestinal, rheumatologic, and dermatologic disorders raises concerns about hepatitis B reactivation (HBVr). The exact risk remains unclear due to the variability in previous meta-analyses. This study aims to assess the effectiveness of antiviral prophylaxis in preventing HBV reactivation in patients on TNF-α therapy and to investigate the associated reactivation risk.

METHOD: A systematic review adhering to PRISMA guidelines will be conducted. Comprehensive searches of electronic databases (MEDLINE via PubMed, Google Scholar, CENTRAL, and ClinicalTrials.gov) will identify relevant studies. Eligible studies will include patients with a hepatitis B infection treated with anti-TNF-α therapy. The efficacy of antiviral prophylaxis will be assessed using risk ratios (RR) with 95% confidence intervals (CI) in a random-effects model that controls for variation among trials. Heterogeneity will be evaluated using the I2 statistic and Cochran's Q test, with I2 > 50% or p < 0.10 indicating significant heterogeneity. Subgroup analyses will explore sources of heterogeneity, such as the type of antiviral medication, HBV serostatus, and the type of anti-TNF agent. Publication bias will be assessed using funnel plots and Egger's test. The incidence of HBV reactivation will be estimated using pooled estimates and 95% CIs in a random-effects model, excluding patients receiving antiviral prophylaxis.

DISCUSSION: The rate of hepatitis B virus (HBV) reactivation varies greatly between chronic and occult carrier states. Despite established practice standards, high-risk individuals still get insufficient preventative antiviral treatment. Current recommendations propose prophylactic nucleoside/nucleotide analogue (NA) prophylaxis for immunosuppressive treatment that has a high risk of reactivating HBV. For low-risk treatments, on-demand NA treatment is recommended. For intermediate-risk drugs, either strategy might be suitable. However, there is an urgent need for agreement on standardized criteria and reporting protocols for HBV reactivation in the setting of immunosuppressive treatments. TRIAL REGISTRATION: Systematic review registration: PROSPERO CRD42024548106.