Introduction: Hepatitis B Virus genotypes influence chronic hepatitis B evolution and show geographic preferences. In Eastern Europe, HBV-D genotype seems to be dominant, still, without enough information regarding the prevalence of its four subtypes. In addition, treatment with Nucleos(t)ide Analogues (NUCs) has lower impact on HBV-D genotype clearance compared to others. This study aimed at presenting the case of a middle age female diagnosed, followed-up and treated for eight years with entecavir 0. 5 mg/day, in whom an increase of anti-HBsAb titer was noted over the immunogenicity level and undetectable viremia, despite the continuous presence of HBsAg. This is an uncommon type of evolution, most patients with anti-HBsAb over 10 IU/mL show seroconversion in the “ s” system in a few months. Case Presentation: The researchers used the COBAS TaqMan HBV Monitor Test (Roche Diagnostics, Branchburg, NJ) in order to measure serum HBV DNA level, then, the viral DNA was extracted from 200 L of serum using QIAamp DNA blood mini kit (Qiagen, Germany). The amplification and sequencing of full DNA length was done by the Rolling Circle Amplification (RCA) technique. Hepatitis B Virus genotype was determined using the NCBI genotyping tool and phylogenetic analysis. Conclusions: The patient was proved to haveDgenotype. TheDNAanalyzes showed escape mutations in the “ a” determinant within the S gene, represented by sQ129R, respectively, sI134T, reported by the literature in a small number of C genotype patients. The paradoxical serum profile of the current patient with positive HBsAg, increased titers of anti-HBsAb, and undetectable viral load could be a possible model of evolution for D genotype HBV chronic infected patients treated with NUCs, cohort genetic studies on patients with the same serum profile are required to confirm this pattern of evolution.