Precision stratification for hepatitis B functional cure: Biomarkers, machine learning and the combination-therapy era

Figure 1 Sources of circulating hepatitis B surface antigen and selected therapeutic targets. Covalently closed circular DNA produces pregenomic RNA and preS/S messenger RNA. Integrated hepatitis B virus DNA can also produce surface antigen, generally without supporting a complete replication cycle. RNA-silencing activity depends on retention of the compound-specific target sequence. Entry inhibitors target sodium taurocholate cotransporting polypeptide; small interfering RNA, antisense oligonucleotides, capsid assembly modulators and immune therapies act at the indicated sites. Solid arrows represent simplified pathways; dashed arrows indicate therapeutic targets[4,6,7,18]. HBV: Hepatitis B virus; NTCP: Sodium taurocholate cotransporting polypeptide; ASOs: Antisense oligonucleotides; siRNA: Small interfering RNA; HBsAg: Hepatitis B surface antigen.