First identification of occult hepatitis B infection among ethnic minority students in Thai Nguyen, Vietnam

Abstract Background Hepatitis B virus (HBV) remains a major health concern particularly in regions with intermediate-to-high endemicity such as Vietnam. Occult hepatitis B infection (OBI) defined as the presence of replication-competent HBV DNA in the absence of detectable hepatitis B surface antigen (HBsAg) poses challenges for diagnosis and blood safety. However, data on OBI among Vietnam’s ethnic minority populations are scarce. Methods A cross-sectional study was conducted among 267 HBsAg-negative ethnic minority students at Thai Nguyen University of Medicine and Pharmacy in 2024. Serum samples were screened for HBV serological markers (anti-HBs, anti-HBc) using commercial ELISAs. HBV DNA was extracted, amplified by nested PCR targeting a conserved S/P region, and sequenced for genotyping and mutational analysis. Quantitative real-time PCR (qPCR) was used to assess viral loads. Results Among participants, 57% were susceptible (anti-HBs–/anti-HBc–), 27% exhibited vaccine-induced immunity, 12% had resolved infections, and 4% showed isolated anti-HBc positivity. Overall, 16% were anti-HBc positive, indicating prior exposure. HBV DNA was detected in two samples (0.7%), both with undetectable viral loads by qPCR. One case represented seronegative OBI and the other seropositive OBI. Phylogenetic analysis classified both isolates as genotype B. Mutational analysis identified substitutions K122R, F200Y, Y206C, and I187V, with S117N uniquely present in one isolate. Conclusions This study provides the first evidence of OBI among ethnic minority students in northern Vietnam. Although prevalence was low, the high proportion of HBV-susceptible individuals highlights ongoing vulnerability and underscores the need for strengthened immunization, awareness, and surveillance programs in underserved communities.