Liver glycogen bodies: ground-glass hepatocytes in transplanted patients

Abstract

Ground-glass hepatocytes have been described in Lafora's disease, fibrinogen deposition, hepatitis B, type IV glycogenosis, and alcohol aversion (cyanamide) therapy. We encountered ground-glass hepatocytes with intracytoplasmic inclusions in four liver biopsies from three transplanted patients who had none of the above-mentioned underlying diseases. One patient was a 4-year-old boy who had a kidney transplant for severe ureterovesical reflux. Patient 2 was a 52-year-old man who had two liver transplants because of hepatitis C. The third patient was a 7-month-old girl who underwent a multivisceral transplant because of necrotizing enterocolitis and liver failure induced by total parenteral nutrition. The patients developed liver abnormalities from 45 days to 4 years after their transplants. The livers showed conspicuous ground-glass hepatocytes in 90% of the children's samples and 30% of the adult liver cells. The cytoplasmic bodies stained strongly for Gomori methenamine-silver; they were positive for periodic acid-Schiff without diastase, but negative after diastase digestion. They were negative for colloidal iron and hepatitis B core and surface antigens. Electron microscopy revealed non-membrane bound aggregates of glycogen. Idiopathic ground-glass hepatocytes occur in transplanted patients and represent accumulation of altered glycogen. However, their clinical significance and cause are not entirely elucidated.

NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. The 2014 Pathology Working Group Report

“…Two unusual manifestations associated with GVHD involve hepatocyte inclusions recognized by periodic acid Schiff (PAS) staining. These include both diastase-sensitive polyglucosan-like ground-glass cytoplasmic inclusions [35, 36] and PAS-positive diastase-resistant pseudo-Lafora bodies thought to represent an unusual form of degenerative organelles and glycogen [37, 38]. Data are insufficient to determine whether IHC staining for replicative senescence by p21 [39], determination of the Th17/T regulatory cell ratio [40], or staining for C4d provides additional information above and beyond the usual histological evaluation [41].…”

Tacrolimus induced hepatotoxicity in a patient with bilateral lung transplant

“…In our patient, the HCV viral load increased significantly after transplant, but did not have inflammatory changes consistent with reactivated HCV infection in liver biopsy. We concluded that our patient’s hepatic dysfunction was due to tacrolimus toxicity because of the following: (i) extensive hepatic work‐up that exclude all other etiologies including hepatic veno‐occlusive disease, (ii) the ground glass hepatocytes found on transjugular liver biopsy [9], and c) the rapid reversal of LFT after tacrolimus was stopped. Ground‐glass hepatocytes have been described earlier with other causes, such as chronic hepatitis B infection, Lafora’s disease, type 4 glycogenosis, cynamide alcohol aversion therapy, and fibrinogen storage disease.…”

“…Ground‐glass hepatocytes have been described earlier with other causes, such as chronic hepatitis B infection, Lafora’s disease, type 4 glycogenosis, cynamide alcohol aversion therapy, and fibrinogen storage disease. There has been report of patients with glycogen inclusions in hepatocytes in patients on multiple immunosuppressive medications, which included tacrolimus [7–10].…”

Ground glass-like inclusions: associated with liver toxicity

“…All of the 12 patients were using polypharmacotherapy, mostly including steroids and tacrolimus (FK506) (4). Similarly, all three patients in the series by Bejarano et al were undergoing multidrug medication including steroids and tacrolimus (9). In summary of the above studies, PAS+ ground glass inclusions have been mostly reported in immunosuppressed patients on multidrug medications in a setting of transplantation and immunosuppression.…”