Background: Hepatitis B virus (HBV) continues to be a significant global health issue,
impacting millions of people around the globe. Although antiviral medications have
greatly enhanced the treatment of chronic HBV infection, the development of antiviral
resistance presents a difficult obstacle to current therapeutic approaches. This review
analyses the progression of antiviral resistance in HBV, providing insight into the
underlying mechanisms and consequences for clinical treatment. The use of nucleos(t)ide
analogues (NAs) and interferon-based therapy represented important achievements in the
management of chronic HBV infection. Nevertheless, the extended utilization of
nucleoside analogues (NAs), such as lamivudine, entecavir, and tenofovir, has been
linked to the emergence of resistance mutations in the gene responsible for viral
polymerase. These modifications provide the virus with a specific benefit, which reduces
the effectiveness of antiviral drugs and requires changes in treatment. Moreover, the
presence of both wild-type and drug-resistant strains inside the same patient exacerbates
the complexity of treatment outcomes. The emergence of HBV antiviral resistance
highlights the significance of diligent surveillance and prompt intervention to enhance
treatment results and presents a substantial risk to current therapeutic approaches.
Continued research endeavours to comprehend the genetic and molecular foundation of
resistance, together with the creation of innovative antiviral substances, are crucial to
tackle this problem and improve the long-term control of chronic HBV infection.