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Background: Polymorphisms of genes encoding the pro-inflammatory and anti-inflammatory cytokines can affect the clinical presentation of the infection. We aimed to assess the role of EGF gene single-nucleotide polymorphism in the outcome of chronic hepatitis B virus (HBV) infection in children. Methods: One hundred HBV-infected children and 75 healthy matched controls were enrolled in this prospective study. Patients included 18 chronic inactive and 82 chronic active carriers. EGF rs4444903 A>G genotypes were determined using allele-specific amplification. Results: Significant differences regarding EGF genotypic frequency (p=0.001) in patients compared to controls (p=0.001). Eighteen percent were inactive, and 82% were active carriers. AA, AG and GG genotypic frequency were 66.7%, 33.3%, 0% and were 3.7%, 37.8% and 58.5% in the inactive and active carriers, respectively, with significant differences regarding AA, AG, GG genotypic frequency (p=0.001 for all). EGF AA, AG, GG genotypes frequency were 1.9%, 33.3%, and 64.8%, respectively, with significant differences between cirrhotic and non-cirrhotic patients regarding AA, AG, GG genotypic frequency (p=0.001 for all). Conclusion: Increased G allele frequency in EGF rs4444903 A > G polymorphism in HBV- Egyptian children is associated with worse outcomes.