title: Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions.
abstract: The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term "recombino-subgenotype". Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term "immigro-subgenotype" to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.
authors: Mahmoud Reza Pourkarim, Marc Van Ranst, Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium.
authors: Mahmoud Reza
authors: MR
authors: Pourkarim
authors: Mahmoud Reza Pourkarim, Marc Van Ranst, Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium.
authors: Samad
authors: S
authors: Amini-Bavil-Olyaee
authors: Mahmoud Reza Pourkarim, Marc Van Ranst, Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium.
authors: Fuat
authors: F
authors: Kurbanov
authors: Mahmoud Reza Pourkarim, Marc Van Ranst, Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium.
authors: Marc
authors: M
authors: Van Ranst
authors: Mahmoud Reza Pourkarim, Marc Van Ranst, Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium.
authors: Frank
authors: F
authors: Tacke
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D004641:Emigration and Immigration; D019143:Evolution, Molecular; D005838:Genotype; D006509:Hepatitis B / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D010641:Phenotype; D010802:Phylogeny
chemical_list: D000998:Antiviral Agents
keywords: Classification; Genotype; Hepatitis; Hepatitis B virus; Phylogenetic tree; Subgenotype