Ground-glass hepatocellular inclusions are associated with polypharmacy

Area of Science:

• Hepatology
• Cellular Pathology
• Biochemistry

Background:

• Ground-glass (GG) hepatocytes are typically associated with chronic hepatitis B (HBV) infection, certain storage disorders, or cyanamide therapy.
• However, the etiology of GG hepatocytes remains unidentified in a subset of cases.
• Characterizing these findings in HBV-negative individuals is crucial for differential diagnosis.

Purpose of the Study:

• To investigate the clinical, histological, and ultrastructural features of HBV-negative GG hepatocytes.
• To identify potential causes and associations in patients without known risk factors for GG hepatocytes.

Main Methods:

• Retrospective review of liver biopsies (2000-2019) with GG hepatocellular inclusions and negative HBV serology.
• Exclusion of patients with known storage disorders or cyanamide therapy.
• Clinical data review, including medication history, and histological/ultrastructural analysis (PAS staining, diastase sensitivity, electron microscopy).

Main Results:

• Ten cases of HBV-negative GG hepatocytes were identified.
• Half of the patients had a history of organ transplantation and/or malignancy, with an average of 8.1 medications.
• Histology revealed peri-portal or centrizonal PAS-positive, diastase-sensitive inclusions consistent with unstructured glycogen on electron microscopy.

Conclusions:

• Ground-glass hepatocytes are a rare finding, more prevalent in HBV infection but also observed in HBV-negative patients with polypharmacy.
• These inclusions represent unstructured glycogen accumulation, likely resulting from altered cellular metabolism in the context of multiple medications.
• Further research into drug-induced metabolic alterations in hepatocytes is warranted.