Our findings, including largely normal histology, consistently normal ALT levels, infrequent Ki67 RNA expression, stable human albumin levels over infection course, and the presence of HBsAg-positive/rcDNA-positive cells lacking detectable cccDNA, suggest that spontaneous cccDNA loss occurs primarily through non-cytolytic mechanisms (58) in most cells that avoided cytopathic consequences, with a minor contribution from cytopathic clearance in a subset of cells with cytopathic effects during persistent HBV infection established in this chimeric mouse model. Here, ALB is linked to infection.