Chronic Hepatitis B Infection: Current and Emerging Therapeutic Strategies

The chronic infection of the hepatitis B virus (CHB) represents a major public health problem worldwide. Despite the availability of an effective prophylactic vaccine, millions of hepatitis B patients are at increased risk of developing chronic liver disease. The currently available treatments for HBV infection include interferon and nucleos(t)ide analogues that are effective at suppressing viral load and preventing or delaying the progression of liver disease. However, these treatments offer somewhat unsatisfactory clinical cures due to the persistence of the intrahepatic pool of covalently closed circular DNA (cccDNA) that serves as a reservoir for viral progenies and a potential source of recurring infections. Elimination of viral cccDNA remains a challenge for scientists and pharmaceutical industries in order to achieve the eradication and control of HBV infection. This would involve a detailed understanding of the molecular mechanisms of cccDNA formation, its intracellular stability, and regulation during replication and transcription. Recent advances in drug therapy have heralded a new horizon of novel therapeutic approaches for CHB infection, with several promising antiviral and immunomodulatory agents currently in preclinical or clinical testing. However, approval of any new curative therapy would involve rigorous evaluation of the efficacy and safety of each treatment and defining correct endpoints associated with improved clinical outcomes. This article summarizes the current landscape of HBV treatments, and drugs in clinical trials and highlights the most recent anti-HBV small molecules designed to directly target HBV or to improve immune response during chronic infection.