glycogen and Hepatitis-B--Chronic

Ground-glass (GG) hepatocytes are classically associated with chronic hepatitis B (HBV) infection, storage disorders, or cyanamide therapy. In a subset of cases, an exact etiology cannot be identified. In this study, we sought to characterize the clinical, histological, and ultrastructural findings associated with HBV-negative GG hepatocytes. Our institutional laboratory information system was searched from 2000 to 2019 for all cases of ground-glass hepatocytes. Ten liver biopsies with GG hepatocellular inclusions and negative HBV serology, no known history of storage disorders, or cyanamide therapy were reviewed. Half of the patients had history of organ transplantation and/or malignancy. These patients took on average 8.1 medications (range: 3-14) with the most common medications being immunosuppressive and health supplements. Histologically, GG hepatocytes show either peri-portal or centrizonal distribution. The inclusions are PAS-positive and diastase sensitive. Electron microscopy showed intracytoplasmic granular inclusions with low electron density, consistent with unstructured glycogen. In summary, GG hepatocytes are a rare finding in liver biopsies, but are more common in patients with hepatitis B. They can also be seen in HBV-negative patients who have polypharmacy. In these cases, they are the result of unstructured glycogen accumulation putatively due to altered cell metabolism.

Topics: Adult; Aged; Biopsy; Carcinoma, Hepatocellular; Chemical and Drug Induced Liver Injury; Child, Preschool; Cyanamide; Cytoplasm; Dietary Supplements; Female; Glycogen; Glycogen Storage Disease; Hepatitis B, Chronic; Hepatocytes; Humans; Immunosuppressive Agents; Inclusion Bodies; Liver; Liver Neoplasms; Male; Microscopy, Electron; Middle Aged; Polypharmacy

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.

Topics: Adult; Child; Child, Preschool; Cytoplasm; Female; Glycogen; Hepatitis B, Chronic; Hepatocytes; Humans; Immunosuppression Therapy; Inclusion Bodies; Male; Middle Aged

Hepatocellular carcinomas elicited in woodchucks by the woodchuck hepatitis virus (WHV) emerge gradually from parenchymal areas of minimal structural deviation via two predominant preneoplastic hepatocellular lineages, composed of either glycogenotic/basophilic or amphophilic/basophilic cell foci. In this study we analyzed WHV replication during neoplastic development in both lineages.. In minimal deviation areas, preneoplastic hepatocellular foci, and hepatocellular neoplasms, developing in 16 WHV-carriers 31-38 months after WHV-inoculation, the proportion of hepatocytes containing WHV replicative intermediates (as detected by in situ hybridization for WHV DNA) and immunoreactive for WHV core and surface antigens was assessed.. Appearance of WHV replicative intermediates and expression of antigens were limited to the cytoplasm of hepatocytes and were strongly correlated (P<0.0001), both showing high levels in minimal deviation areas, but markedly reduced amounts in all types of preneoplastic hepatic focus (P<0.0001), and in hepatocellular adenomas. Most hepatocellular carcinomas were negative for WHV replicative intermediates and antigens.. In both the glycogenotic-basophilic and the amphophilic-basophilic preneoplastic hepatocellular lineage, WHV replication and antigen expression gradually decrease early during the preneoplastic phase. The close correlation of these changes with metabolic aberrations characterizing preneoplastic hepatocellular lineages suggests that oncogenic effects mimicking insulin/glucagon imbalances may be responsible for the repression of hepadnaviral replication.

Topics: Adenoma, Liver Cell; Animals; Cell Lineage; DNA, Viral; Glycogen; Hepatitis B Antigens; Hepatitis B Virus, Woodchuck; Hepatitis B, Chronic; Hepatocytes; In Situ Hybridization; Liver Neoplasms; Marmota; Precancerous Conditions; Virus Replication

To correlate the in vivo hydrogen 1 ((1)H) magnetic resonance (MR) spectroscopic features of the chronic hepatitis-involved liver with the histopathologic stages of fibrosis.. Seventy-five patients with chronic hepatitis were examined with (1)H MR spectroscopy, which was performed in the right hepatic lobe. The peak areas of glutamine and glutamate complex (Glx), phosphomonoesters (PME), glycogen and glucose complex (Glyu), and lipid were measured on the liver spectra. The histopathologic features were correlated with the in vivo (1)H MR spectroscopic findings at each stage of chronic hepatitis. Fifteen healthy volunteers also were included as a control group.. (1)H MR spectroscopy depicted Glx, PME, Glyu, and lipid in all livers. In the normal livers, the calculated mean (+/- SD) relative metabolite-to-lipid ratios of Glx, PME, and Glyu were 0.14 +/- 0.04, 0.03 +/- 0.01, and 0.21 +/- 0.04, respectively. The mean value of each metabolite-to-lipid ratio was significantly different between all stages of chronic hepatitis, and with the exception of the mean ratio at the interval between stages 0 and 1 (P > .05), the mean value increased significantly with increasing stage (P < .05). A pronounced peak was demonstrated at 3.9-4.1 ppm at (1)H MR spectroscopy of all stages of chronic hepatitis except stage 0.. The increased Glx, PME, and Glyu levels relative to the lipid content with chronic hepatitis indicated the severity of fibrosis and thus were concordant with the histopathologic stages. In vivo (1)H MR spectroscopy might be a substitute for liver biopsy in the diagnosis and staging of chronic hepatitis.

Topics: Adolescent; Adult; Biopsy; Female; Glucose; Glutamic Acid; Glutamine; Glycogen; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Lipids; Liver; Liver Cirrhosis; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphates