Diagnosis: Ground-Glass Hepatocytes in Chronic Hepatitis B
• Ground-glass cytoplasmic inclusions in hepatocytes are a characteristic histopathologic feature of chronic hepatitis B, with or without cirrhosis.
• Cytoplasmic ground-glass inclusions of HBsAg can be confirmed by specific immunoperoxidase staining; this should always be accompanied by immunostaining for hepatitis B core antigen (HBcAg) to evaluate the tissue evidence of active viral replication. When many hepatocyte nuclei show positive staining for HBcAg or there is also accompanying cytoplasmic staining, active viral replication is present. Patients with these findings often have high levels of serum hepatitis B virus DNA and are positive for hepatitis B early antigen (HBeAg); HBeAg is another indicator of ongoing active viral replication.
• The differential diagnosis of ground-glass hepatocellular inclusions includes cyanamide alcohol aversion therapy, glycogen or abnormal glycogen inclusions (polyglucosan bodies) in type IV glycogen storage disease or in patients treated with polypharmacy after liver transplantation, Lafora disease (myoclonic epilepsy), and fibrinogen storage disease.
• If specific antibody to HBsAg and orcein or Victoria blue stains are negative in a biopsy specimen with ground-glass inclusions, other stains such as colloidal iron and Periodic acid–Schiff (PAS) may be helpful in diagnosis. Colloidal iron and PAS stains are usually positive in the ground-glass inclusions on biopsy specimens from patients with Lafora disease or posttransplant polypharmacy.
