Chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide as well as a therapeutic challenge (1 ). HBV belongs to the hepadnavirus family and replicates its DNA genome via a reverse transcription step (2 ). The spontaneous error rate of the viral reverse transcriptase is responsible for the evolution of the viral genome during the course of infection under the antiviral pressure of the host immune response or specific therapy (3 ). Eight major viral genotypes, A to H, have been identified (4 ) as well as many mutants, some of which have important clinical implications (3 ). In clinical practice, the most frequently encountered variant form of chronic HBV infections is the hepatitis B e antigen (HBeAg)-minus chronic hepatitis B associated with the replication of precore stop codon mutants that terminate preC/C protein (HBeAg precursor) expression (5 –8 ).