Abstract
The hepatitis B virus (HBV) genotype D (HBV/D) is the most extensively distributed genotype worldwide with distinct molecular and epidemiological features. This report provides an up-to-date review on the history of HBV/D subgenotyping and misclassifications, along with large-scale analysis of over 1000 HBV/D complete genome sequences, with the aim of gaining a thorough understanding of the global prevalence and geographic distribution of HBV/D subgenotypes. We have additionally explored recent paleogenomic findings, which facilitated the detection of HBV/D genomes dating back to the late Iron Age and provided new perspectives on the origins of modern HBV/D strains. Finally, reports on distinct disease outcomes and responses to antiviral therapy among HBV/D subgenotypes are discussed, further highlighting the complexity of this genotype and the importance of HBV subgenotyping in the management and treatment of hepatitis B.