Currently, there are two therapeutic strategies approved for HBV treatment: five nucleos/tide analog reverse-transcriptase inhibitors, or NRTIs (lamivudine, telbivudine, entecavir, adefovir, and tenofovir), which inhibit the HBV genome replication, and the immune-based therapy that includes standard and pegylated interferon-α (IFN-α). Both treatments are not capable of eradicating chronic HBV infection and curing patients, or even of efficiently controlling the infection. IFN therapy is associated with low response rates, liver decompensation and numerous (often severe) side effects, while NRTIs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. An effective treatment is still not available, and chronic hepatitis B remains a serious clinical problem worldwide.
Available antiviral options suppress viral replication and improve patient survival, but they do not eradicate the virus and the cccDNA pool, which results in viral reactivation after cessation of treatment and in the development of liver disease progression. The goal of new therapeutic strategies is to eliminate or control HBV and to allow access to therapy in poor, high-endemicity areas, where the consequences of HBV infection are more severe. Current research efforts focus on the identification of novel compounds that inhibit viral entry, viral polymerase, nucleocapsid assembly, reverse transcription, cccDNA formation and stability, viral RNA encapsidation, immune system modulators, small interfering RNAs, cyclophilin inhibitors and more.