Serological and Demographic Correlates of HBV DNA Detection Below the Limit of Quantification in Treated Chronic Hepatitis B and HBsAg-Negative Patients.

Objectives: This study aimed to evaluate very low HBV DNA viral load below the limit of quantification and to identify correlational factors in different patient groups, including individuals with chronic hepatitis B (CHB), occult HBV infection (OBI), and others. Methods: We retrospectively analyzed 390 patients with very low-level viremia (VLLV). HBV DNA levels were measured in plasma samples using real-time quantitative PCR (qPCR). Serological markers were evaluated in serum samples using chemiluminescence microparticle immunoassay (CMIA). Demographic variables, HBV serological markers (anti-HBs, anti-HBe, anti-HBc), and DNA results were evaluated. Results: The study included 193 CHB patients with maintained virological suppression and 197 patients in the other group; of which, 60 patients had occult hepatitis B infection (HBV DNA positive, HBsAg negative) and 137 had no occult hepatitis B infection. Very low viral load was more common in men (53.3%) and in individuals aged ≥50 years (63.3%). In univariate analysis, OBI was associated with anti-HBe (odds ratio (OR) = 2.874, 95% CI: 1.255-6.579, p = 0.013), and anti-HBc seropositivity (OR = 5.750; 95% CI: 2.626-12.591, p < 0.001). In multivariate analysis, anti-HBe positivity and anti-HBc positivity were independently associated with OBI. Anti-HBs positivity was independently and inversely associated with OBI. Conclusions: In patients with VLLV cohort, anti-HBc and anti-HBe seropositivity were independently associated with detectable but unquantifiable HBV DNA. Although anti-HBe positivity reflects reduced viral replication, it does not indicate complete viral suppression and may be detected at very low viremia levels, especially in occult HBV infection. These findings highlight the complex interplay between viral replication dynamics and host immune responses across the VLLV spectrum, characterize the serological landscape associated with detectable but unquantifiable HBV DNA, and warrant validation in prospective studies.