Review of Expected Drug Targets and Targeted Drug Treatments for Hepatitis B

Chronic hepatitis B virus infection, which affecting over 300 million people globally, is strongly linked to hepatocellular carcinoma (HCC). HBV, partially double-stranded smal DNA virus, targets hepatocytes and will progress to liver cirrhosis and HCC. Although significant advancements have been made in antiviral therapy, a definitive cure remains elusive, primarily because of the persistence of covalently closed circular DNA (cccDNA). Significantly burdening patients and healthcare systems due to monitoring needs, drug resistance risks, and side effects. Current therapeutic options, including interferon- and NRTIs, provide only partial viral suppression and require lifelong treatment. Emerging therapeutic strategies, such as entry inhibitors, polymerase inhibitors, capsid assembly modulators, and gene-editing tools, are being engineered to address various phases of the HBV life cycle. Notably, CRISPR/Cas9 has shown promising potential for cccDNA eradication in preclinical studies. Aiming for the "functional cure," combination therapies involving these novel agents are defined by the sustained loss of hepatitis B surface antigen (HBsAg) after treatment cessation. The review provides a comprehensive overview of the HBV life cycle, current information and emerging therapeutic strategies, and the potential of combination therapies to enhance treatment efficacy. However, achieving complete viral eradication remains a significant challenge, underscoring the need for continued research into novel therapeutic approaches.