Genetic Diversity, Occult Hepatitis B, and Mutational Signatures in Migrants from Regions with Varying HBV Endemicity: Importation of Diverse Viral Variants into St. Petersburg, Russia

The importation of hepatitis B virus (HBV) variants through migration challenges elimination efforts in low-endemicity countries. This study evaluated the seroprevalence, occult hepatitis B infection (OBI), and molecular signatures of HBV among 537 international migrants from 46 countries who arrived in St. Petersburg, Russia. HBsAg, anti-HBs, and anti-HBc were measured by ELISA. This was followed by nested real-time PCR targeting viral genes (S, X) and a human housekeeping gene (HPRT, internal control), amplification of overlapping fragments covering the complete HBV genome, and Sanger sequencing. HBsAg prevalence was 2.61% (95% CI: 1.43–4.34), while anti-HBc was detected in 16.39% (95% CI: 13.36–19.79). HBV DNA was found in 8.19% (44/537; 95% CI: 6.02–10.04) of migrants. Notably, OBI (HBsAg-negative/HBV DNA-positive) was identified in 33 individuals, yielding a prevalence of 6.15% (33/537; 95% CI: 4.27–8.52) in the entire cohort and 6.31% among HBsAg-negative subjects. The findings among OBI cases were as follows: the majority (54.5%) had no detectable anti-HBc or anti-HBs; 30.3% were positive for anti-HBs only; 6.06% were positive for anti-HBc IgG only; 9.09% of cases featured both anti-HBc and anti-HBs. Viral loads in OBI cases were uniformly low (14–53 IU/mL). Genotype D predominated (86.36%, 38/44). The distribution of subgenotypes among all sequenced isolates was as follows: D1 in 36.36% (16/44), D2 in 36.36% (16/44), D3 in 13.64% (6/44), while genotypes A2 (6.82%, 3/44), B4 (4.55%, 2/44), and C2 (2.27%, 1/44) were rare. In the major hydrophilic region (MHR), the most frequent amino acid substitutions were at positions T127P/I (61.4%) and T118R/M/V/A (45.5%). Immune escape mutations were significantly associated with OBI (81.82% of OBI cases versus 18.18% of HBsAg-positive cases; p = 0.003). Drug resistance mutations (L180M + M204V ± T184A) were detected in 11.4% of isolates (all genotype D2). In the precore region, stop codon mutation W28* was found in 31.82% of samples, and the A1762T/G1764A double substitution in the basal core promoter occurred in 25.0%. The high prevalence of OBI, coupled with the accumulation of escape and drug resistance mutations in imported HBV variants, highlights the urgent need to include molecular HBV screening in mandatory medical examinations for arriving migrants to prevent undetected transmission and inform clinical management in receiving countries.