Hepatitis B surface antigen inclusions on Victoria blue stain appear as homogeneous (not granular) crescentic intracytoplasmic inclusions in hepatocytes, usually randomly distributed throughout the parenchyma and not localized in periportal hepatocytes. Chronic hepatitis B is usually not associated with chronic biliary obstruction and impaired copper excretion.
There is impaired egress of bile (including the copper in bile) from the liver in late, chronic cholestatic disorders including PSC and primary biliary cirrhosis (PBC), resulting in periportal copper overload. There is resultant upregulation of synthesis of an intralysosomal metallothionein protein (i.e., copper-binding protein, stainable with Victoria blue stain), which sequesters copper and decreases the likelihood of hepatocellular damage from copper retention.
Cardiac hepatopathy refers to the congestion, sinusoidal dilatation, and related perivenular (i.e., centrilobular) fibrosis associated with chronic cardiac disease; hepatic copper overload is not a feature.
Significant copper overload that is associated with significant periportal copper-binding protein staining on Victoria blue stain is not seen until the late stages (i.e., stage 3 or 4) of PBC.
The periportal globules of AAT seen in AAT deficiency are stained with diastase-pretreated Periodic acid–Schiff (PAS) stain, not Victoria blue stain. The globules of AAT deficiency are highly variable in size, whereas granules of copper-binding protein on Victoria blue stain are very small and uniform.