Hepatitis B in Isolated Anti-HBc Carriers: Predictors of Detectable HBV DNA and Implications for Risk-Stratified Screening

Background/Objectives: Isolated anti-HBc (IAHBc)—anti-HBc reactivity without HBsAg or anti-HBs—may indicate occult HBV infection (OBI) and confers reactivation risk under immunosuppression, yet most evidence derives from single specialties. We assessed the frequency, predictors, and diagnostic yield of detectable HBV DNA across multiple clinical specialties in a large real-world cohort to inform risk-based testing. Methods: In this 8-year, single-center retrospective study from an intermediate-endemic setting, 36,506 patients were screened for HBsAg, anti-HBs, and anti-HBc IgG. Patients with the IAHBc pattern who underwent HBV DNA testing formed the analytic cohort. Predictors of HBV DNA positivity were identified by multivariable logistic regression, and the number needed to screen (NNS) was calculated per specialty. Results: IAHBc prevalence was 4.16% (1517/36,506); 1412 patients comprised the analytic cohort (median age 60 years; 55.2% male). HBV DNA was detectable in 117 patients (8.3% of the cohort; 0.32% of all screened). Positivity varied more than fifteen-fold across specialties, with NNS ranging from 4.3 in gastroenterology to 66 in other clinics. High-intensity immunosuppression was the strongest independent predictor (adjusted OR 14.5), alongside younger age and gastroenterology or infectious diseases referral; the model showed good discrimination (AUC 0.810), while male sex was not an independent predictor. Among positive patients, 47% had HBV DNA below 200 IU/mL, consistent with low-level occult infection. Conclusions: These findings support guideline-recommended HBV DNA testing in all anti-HBc-positive patients before immunosuppression and, where universal testing is not feasible, provide local denominators for prioritizing it as an exercise in diagnostic stewardship. The proposed algorithm is institution-level rather than generalizable.