Evolution is a natural event that enables the animal and plant kingdoms to adapt and survive to changing environmental effects. The same evolutionary pressures also help to shape micro-organisms, including viruses. The evolutionary significance of virus infections has been a subject of discussion for decades1; however, modern genomic analysis became an important focus of research when it became apparent that genetic variants of viruses could be linked to pathogenesis and disease progression. The first questions relating virus diversity to disease progression were provided by Pierre Lépine in 1938 who reported on the evolution of different strains of rabies viruses and a link between different characteristics of infectivity and virulence.2 Recent reports have also revealed the importance of viral evolution and genetic diversity in the pathogenesis of viral diseases, in particular, of RNA (influenza virus, HCV)3 ,4 and retrovirus infections (HIV).5 Hepatitis B virus (HBV) utilises a reverse transcription strategy that, together with an error-prone viral polymerase, has the potential to generate a large number of genetic variants. Chronic HBV (CHB) infection follows four complex dynamic phases, namely immune tolerance, immune clearance, immune control/inactive state and immune escape/reactivation that evolve over several decades. This scenario is usually accompanied by HBeAg seroconversion. The frequency and severity of hepatitis flares can predict disease progression, while early HBeAg seroconversion confers a favourable outcome, and late or absent HBeAg seroconversion results in progression to severe liver disease, such as cirrhosis. …