Hepatitis B functional cure: Current and future perspective

Figure 1 Clinical benefits of a functional cure in chronic hepatitis B. A functional cure leads to multiple favorable outcomes, including reduced risk of cirrhosis, hepatocellular carcinoma, and hepatic decompensation. It also enables treatment discontinuation, durable virological response, improved liver histology, reduced transmission risk, and enhanced quality of life. HCC: Hepatocellular carcinoma; HBV: Hepatitis B virus.

Figure 2 This schematic illustrates key steps in the hepatitis B virus life cycle and corresponding therapeutic intervention points. The virus enters hepatocytes, forms Covalently closed circular DNA (cccDNA) in the nucleus, and undergoes transcription, translation, encapsidation, and release. Potential therapeutic targets include entry inhibition (e.g., Myrcludex B), cccDNA silencing (e.g., clustered regularly interspaced short palindromic repeats-Cas), post-transcriptional suppression (e.g., small interfering RNAs, antisense oligonucleotides), polymerase inhibition (e.g., tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir), capsid assembly modulation (e.g., core protein allosteric modulators), release inhibition (e.g., nucleic acid polymers), and immune modulation strategies (e.g., therapeutic vaccines and checkpoint inhibitors). These interventions aim to disrupt viral persistence and promote functional cure. HBV: Hepatitis B virus; cccDNA: Covalently closed circular DNA; siRNA: Small interfering RNA; ASO: Antisense oligonucleotide; TAF: Tenofovir alafenamide; TDF: Tenofovir disoproxil fumarate; ETV: Entecavir; CpAM: Core protein allosteric modulator; NAP: Nucleic acid polymer; NTCP: Sodium taurocholate co-transporting polypeptide.