Biological interpretation of baseline hepatitis B surface antigen and cirrhosis in determining interferon treatment duration

Table 1 Key unresolved issues in biologically guided interferon treatment stratification

Issue	Why unresolved
Baseline HBsAg	Reflects both cccDNA activity and integrated HBV DNA, so it is not a complete surrogate of viral burden or immune status
Cirrhosis classification	Binary clinical definitions do not capture histological heterogeneity
Non-invasive markers	Existing markers reflect only part of the viral, inflammatory, and structural landscape
Hepatic remodeling	Mechanistic plausibility exists, but direct evidence remains limited
Integrated models	A robust framework combining viral, structural, and immune factors is still lacking

HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus.