Background: Genotypically, hepatitis B virus (HBV) is divided into 8 groups, A–H. The interaction between HBV replication and immune responses against HBV infection plays an important role in the pathogenesis of virus infection. Aims and Objectives: In an attempt to elucidate the role of immunomodulatory, pro-inflammatory, and anti-inflammatory mediators in the pathogenesis of HBV genotype D fulminant hepatitis (FH), we assessed the role of interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) in such patients. Subjects and Methods: Two hundred and seventy-six cases of acute hepatitis among which 37 cases of fulminant hepatic failure were screened. A genotyping system based on polymerase chain reaction using type-specific primers was used in this study (Sami et al. 2013). TNF-α, IL-10 levels, and IFN-γ serum level were measured by ELISA. Results: Genotype D was detected in 10 cases (27.02%) out of 37 FH patients. Mean IL-10, IFN-γ, and TNF-α levels in FH patients were significantly higher than the healthy controls at 127.6 ± 73.45 pg/ml (P