Serological and Molecular Epidemiology of Hepatitis B, C, and D Viruses in Northwest Russia: A Population-Based Cross-Sectional Study.

The hepatitis B (HBV), C (HCV), and D (HDV) viruses remain a major public health burden. Occult HBV infection (OBI) represents a hidden reservoir with clinical and epidemiological significance, yet its prevalence in Northwest Russia is unknown. We aimed to comprehensively assess the serological and molecular epidemiology of HBV, HCV, and HDV in St. Petersburg and the Leningrad region. Methods. In this cross-sectional study, 6773 apparently healthy volunteers were enrolled. Plasma samples were tested for hepatitis B surface antigen (HBsAg), antibodies to HBV core antigen (anti-HBc), antibodies to HBsAg (anti-HBs), antibodies to HCV (anti-HCV), and antibodies to HDV (anti-HDV) by ELISA. All anti-HCV- and anti-HDV-positive samples were tested for HCV RNA and HDV RNA by real-time PCR. All samples were tested for HBV DNA using a highly sensitive in-house nested real-time PCR assay (detection limit: 5 IU/mL). All "HBV DNA-positive, HBsAg-negative" cases confirmed by two independent extractions were classified as OBI. Vaccination status, self-reported history, and iatrogenic interventions were recorded. Results. Overall seroprevalence values were: HBsAg 1.7%; anti-HBc 11.3%; anti-HBs 43.0%; anti-HCV 1.9%; and anti-HDV 0.6%. Anti-HBc increased sharply with age (3.1% in children to 26.4% in the elderly, p < 0.0001), while anti-HBs declined (69.9% to 29.8%, p < 0.0001). HBV DNA was detected in 118 participants (1.7%). Of these, only 73 individuals (1.1%) were HBsAg-positive, while the remaining 45 participants (0.7%) had undetectable HBsAg, meeting the criteria for OBI. OBI was detected across all age groups, including children. Serological profiling of OBI cases revealed that 57.8% lacked both anti-HBc and anti-HBs, 35.6% had isolated anti-HBs, 2.2% had isolated anti-HBc, and 4.4% had both antibodies. HCV RNA was detected in 15.0% of anti-HCV-positive individuals (all adults). No HDV RNA was detected. Self-reported history underestimated true infection rates: 1.4% of those denying HBV infection were HBsAg-positive and 10.6% were anti-HBc-positive. Among those denying HCV infection, 1.4% were anti-HCV-positive. Vaccination coverage was 70.8%, declining from 90.9% in children to 39.0% in the elderly (p < 0.0001). Among vaccinated individuals, 48.0% lacked protective anti-HBs (<10.0 mIU/mL). Conclusions. This comprehensive serological and molecular study in Northwest Russia is the first to combine population-level serology with molecular detection of HBV, HCV, and HDV, including OBI in this region, and reveals that OBI accounts for a substantial proportion (38%) of all active HBV infections and is strongly associated with a history of iatrogenic interventions. The presence of OBI across all age groups, including children, shows that HBsAg screening alone substantially underestimates the true HBV burden. High rates of unrecognized infection and waning vaccine-induced immunity, highlight critical gaps in current surveillance. These findings provide an evidence-based rationale for integrating molecular testing into screening algorithms and for considering booster vaccination strategies to achieve viral hepatitis elimination goals.