Glycogen Pseudoground Glass Change in Hepatocytes

Abstract

Ground glass cytoplasmic change in hepatocytes is typically associated with chronic hepatitis B infection. We report 12 cases of glycogen pseudoground glass change that closely mimics hepatitis B inclusions. Nine individuals were immunosuppressed secondary to liver or kidney transplant (N=3), bone marrow transplant (N=2), HIV infection (N=2), kidney dialysis (N=1), or chronic inflammatory bowel disease (N=1). Medication history was available in 10 individuals and all were on multiple medications (range 2 to 33). Histologically, the pseudoground glass change was identical to the ground glass change seen in chronic hepatitis B infection, with distinct, circumscribed, gray-glassy inclusions surrounded by a rim of cytoplasm. The background livers showed mild or no inflammation and mild or no fibrosis. All cases were negative for chronic hepatitis B infection. The pseudoground glass change was PAS positive and diastase sensitive. Electron microscopy of the inclusions showed glycogen in 3/3 cases. No evidence for viral particles or significant endoplasmic reticulum proliferation was seen. Three cases had follow-up biopsies (1, 1, and 36 mo), and the pseudoground glass was persistent in 2 cases and showed partial resolution in 1 case (1 mo biopsy interval). We conclude that glycogen pseudoground glass change is typically seen in immunosuppressed individuals on numerous medications. The changes are generally seen in the background of mild chronic hepatitis with mild or no fibrosis. Glycogen pseudoground glass change can resolve, but may also persist for years.

Ground-glass-like hepatocellular inclusions in the course of adult-onset Still’s disease

“…In reported patients, other than HBV, the underlying pathophysiology regarding GGH is largely attributed to the glycogen accumulation in hepatocytes [2][3][4]. It is not known whether this condition reflects hepatocyte adaptation or hepatocyte injury [2]. On the other hand, our case reflects some similarities with patients requiring transplantation, as both diseases require immunosuppressives such as high-dose corticosteroids.…”

“…In our case, serology and HBsAg staining with respect to HBV infection were negative, and clinical and laboratory findings as well as patient history were unlikely for the diagnosis of above mentioned diseases. In reported patients, other than HBV, the underlying pathophysiology regarding GGH is largely attributed to the glycogen accumulation in hepatocytes [2][3][4]. It is not known whether this condition reflects hepatocyte adaptation or hepatocyte injury [2].…”

“…She fulfilled all major and minor diagnostic criteria for AOSD [7], and she underwent liver biopsy because of increasing liver enzyme levels despite treatment. GGH appearance is the cardinal biopsy feature of chronic HBV infection and may also be present in other specific conditions, including Lafora's disease (myoclonus epilepsy), cyanamide aversion therapy for alcohol use, patients with transplantation, uremia, and metabolic disorders (glycogenosis type IV and fibrinogen storage diseases) [2][3][4]. In our case, serology and HBsAg staining with respect to HBV infection were negative, and clinical and laboratory findings as well as patient history were unlikely for the diagnosis of above mentioned diseases.…”

“…GGH represents a histological hallmark of chronic hepatitis B virus (HBV) infection and has also been described in a limited number of diseases [2][3][4]. On the other hand, adult-onset Still's disease (AOSD) is an inflammatory rheumatic disease that presents with a variety of symptoms, including fever, rash, sore throat, arthritis, lymphadenopathy, and organomegaly [5,6].…”

Ground Glass Hepatocellular Inclusions Caused by Disturbed Glycogen Metabolism in Three Children on Parenteral Nutrition

“…Recently they have been described in a more diverse context, often associated with polypharmacy and immunosuppression, with the hypothesis that they arise as a result of deranged glycogen metabolism [1,2]. An imbalance in the activities of glycogen synthase (GS) and glycogen branching enzyme (GB) has been shown to produce an abnormal product in mice with a reduced number of branches [3].…”