Molecular Insights Into the S Gene of Hepatitis B Virus: Analysis Among Household Contacts and Clinical Implications of Mutations

Occult hepatitis B infection (OBI) represents a unique diagnostic and clinical challenge due to undetectable HBsAg despite HBV DNA presence. Genetic mutations, particularly in the HBV S gene, play a crucial role in immune evasion and diagnostic failures associated with OBI. This cross-sectional study investigated the genetic mutations in the S gene of HBV among family members of chronically infected patients. This study enrolled 243 family members from 62 HBV-infected index cases. Serological assays were used to identify HBsAg and anti-HBc positivity. HBV DNA was amplified and sequenced in 12 cases, focusing on the S gene. The impact of mutations in the S gene was assessed through in silico analyses, including epitope prediction and secondary structure modelling. Of the household contacts, 9.05% were HBsAg-positive and 37.03% were suspected OBI due to anti-HBc positivity. Out of the suspected OBI, 20% of individuals had detectable HBV DNA. Mutations like R122K and V194A were found to be enriched among OBI sequences and were shown to alter immune epitopes without affecting protein structure. Genotype D was predominant in chronic cases, while genotype A was more frequent in OBI. The adw2 serotype was commonly observed in OBI cases. Thus, this study highlights the role of S gene mutations in OBI's diagnostic and immune escape mechanisms. The findings underline the importance of genotype-specific diagnostic approaches and further investigations into the pre-S regions to enhance understanding of HBV pathogenesis.