Liver Disease in Cytomegalovirus Mononucleosis: A Light Microscopical and Immunoperoxidase Study of Six Cases

Snover, Dale C.; Horwitz, Charles A.

doi:10.1002/hep.1840040309

Cited by 72 publications

(13 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It can be diagnosed by a positive anticytomegalovirus IgM or a fourfold increase in IgG titre, isolation of virus in a culture, via qualitative or quantitative PCR, immunofluorescent assay of cytomegalovirus pp65 antigen in blood or in situ hybridisation and by cytopathology showing the ‘owl's eye’ intracellular inclusion or positive immunohistochemical staining of the cytomegalovirus antigen. In liver biopsy specimen of immunocompetent patients, the finding of typical cytomegalovirus nuclear inclusions and immunohistochemical staining for cytomegalovirus antigen may be absent in acute cytomegalovirus hepatitis as previously reported 9. The pathogenesis behind these findings is thought to be active destruction of infected cells by the immunocompetent cellular immune system.…”

Section: Discussionsupporting

confidence: 65%

Acute cytomegalovirus hepatitis in an immunocompetent host

Omobomi

Lenox

et al. 2013

BMJ Case Reports

View full text Add to dashboard Cite

SUMMARYA 52-year-old woman presented with a 1-week history of recurrent fevers and joint pains accompanied by abdominal and low back discomfort. She has a history of hypoparathyroidism and is on calcium supplements. Physical examination revealed fever and tachycardia. The rest of the examination was normal. Laboratory tests showed newly increased transaminase activity. Serum bilirubin and prothrombin time were normal. She was admitted for evaluation of acute hepatitis. Serology for hepatitis A, B, C and HIV were negative. Her serum acetaminophen and alcohol were undetected. Abdominal imaging was normal. Cultures were sterile. Additional tests for uncommon viral hepatitis included herpes simplex virus, cytomegalovirus and Epstein-Barr virus. Liver biopsy revealed non-specific inflammation. Subsequently, cytomegalovirus serology showed an IgM positive and negative IgG titre. Cytomegalovirus DNA qualitative PCR was also positive. No antiviral medication was given. She continued to have intermittent daily fever but reported no associated symptoms. She was discharged 9 days after admission in stable condition per her request with the advice to follow-up in the clinic in 1 week. Her serum hepatic profile returned to normal and she reported no more episodes of fever. Repeated titres of cytomegalovirus serology showed seroconversion. BACKGROUND

show abstract

Section: Discussionsupporting

confidence: 65%

Acute cytomegalovirus hepatitis in an immunocompetent host

Omobomi

Lenox

et al. 2013

BMJ Case Reports

View full text Add to dashboard Cite

show abstract

“…36,37 HCMV infection causes a mild disease that can be associated with hepatitis in immunocompetent hosts, 38,39 but it is a life-threatening disease in immunosuppressed patients, including transplantation and AIDS patients.…”

Section: Discussionmentioning

confidence: 99%

A single viral protein HCMV US2 affects antigen presentation and intracellular iron homeostasis by degradation of classical HLA class I and HFE molecules

Arieh

Laham

Schechter

et al. 2003

Blood

View full text Add to dashboard Cite

HFE is a nonclassical class I molecule that associates with ␤2-microglobulin (␤2m) and with the transferrin receptor. HFE accumulates in transferrin-containing endosomes, and its overexpression in human cell lines correlates with decreased transferrin receptor (TFR)-mediated iron uptake and decreased intracellular iron pools. A mutation that interferes with proper folding and assembly of HFE complexes results in a severe iron-overload disease hereditary hemochromatosis. We previously suggested that viruses could also interfere with iron metabolism through the production of proteins that inactivate HFE, similarly to classical class I proteins. In particular, we demonstrated in a transient expression system that human cytomegalovirus (HCMV) US2 targeted HFE for proteasomal degradation. Here we demonstrate that the stable expression of HCMV US2 in HEK 293 cells constitutively expressing HFE leads to loss of HFE expression both intracellularly and on the cell surface, and the significant reduction of classical class I expression. Both HFE and classical class I molecules are targeted to degradation via a similar pathway. This HCMV US2-mediated degradation of HFE leads to increased intracellular iron pools as indicated by reduced synthesis of TfR and increased ferritin synthesis. Whether this interference with regulation of iron metabolism potentiates viral replication and/or promotes damage of HCMV-infected tissues remains to be determined. Nevertheless, the deleterious effect of US2 on the expression of HFE and classical class I major histo-compatibility complexes ( IntroductionHuman cytomegalovirus (HCMV) down-regulates the surface expression of major histocompatibility complex (MHC) class I molecules. 1-3 Analysis of HCMV deletion mutants led to the identification of genes within the short segment of the HCMV genome, ie, US2, US3, US6, and US11 that independently mediate this effect. [4][5][6][7][8][9][10][11] Two of these gene products, US2 and US11, target class I heavy chains for dislocation from the endoplasmic reticulum (ER) to the cytosol. 6,7 The heavy chains are deglycosylated by N-glycanase and, subsequently, degraded by the proteasome. The general mode of action of the 2 proteins seem to be similar, but they differ in their ability to attack allelic class I heavy chain gene products. 12 It has been suggested that US2 and US11 specifically down-regulate molecules that are associated with classical antigen presentation pathways because they preferentially promote the degradation of HLA-A and -B loci products relative to those encoded by Supporting the association of HCMV US2 with reduced antigen presentation by HCMV-infected cells and their escape from specific immune responses are data showing that US2 also down-regulates class II MHC DM␣ and DR␣ molecules. 16,17 Most effects of US2 were demonstrated using an astrocytoma cell line; however, recently both US2 and US11 have been shown to down-regulate class I, but not class II, MHC molecules in human dendritic cells. 18 We have previously observed that US...

show abstract

“…119 Phlebotomy has been shown to improve or normalize liver enzyme abnormalities in these patients. 122,123 Liver infection by other herpes viruses, adenovirus, and bacteria and fungi, may occur following HCT, but the morphologic changes associated with such infections would not be expected to cause confusion with GVHD. 121 Although HCT patients are susceptible to liver infection due to opportunistic and other organisms, unlike in the GI tract, the morphologic changes occurring in this setting do not usually mimic those related to GVHD.…”

Section: Iron Overloadmentioning

confidence: 99%

Hematopoietic Stem Cell Transplantation

Kambham

Higgins

Sundram

et al. 2014

Advances in Anatomic Pathology

View full text Add to dashboard Cite

Hematopoietic stem cell transplantation (HCT), formerly known as bone marrow transplantation, is an integral part of treatment for many hematological malignancies. HCT is associated with several complications and comorbidities with differential effects on a wide spectrum of organs and tissues. We present an update on HCT-associated complications such as graft versus host disease (GVHD) and infection, with focus on the surgical pathology of the gastrointestinal (GI) tract, liver, and lung. Although the grading system for GI tract acute GVHD was proposed 40 years ago, recent studies have shed light on minimal histologic criteria for diagnosis of GVHD, as well as its differential diagnosis, including histologic effects of various medications. GI dysfunction in autologous transplant recipients is increasingly appreciated and patients are often biopsied. Acute liver injury in HCT is often due to sinusoidal obstruction syndrome (previously known as venoocclusive disease), or acute GVHD. Liver dysfunction at later time posttransplantation may be associated with acute or chronic GVHD, iron overload, or other causes of hepatitis. Lung injury in HCT is multifactorial, and it remains crucially important to diagnose and treat pulmonary infections. The pulmonary biopsy yields clinically unsuspected diagnoses in the majority of cases and its utilization is likely to increase. The pathology of the skin and kidney in HCT patients are detailed in accompanying articles.

show abstract

Liver Disease in Cytomegalovirus Mononucleosis: A Light Microscopical and Immunoperoxidase Study of Six Cases

Cited by 72 publications

References 15 publications

Acute cytomegalovirus hepatitis in an immunocompetent host

Acute cytomegalovirus hepatitis in an immunocompetent host

A single viral protein HCMV US2 affects antigen presentation and intracellular iron homeostasis by degradation of classical HLA class I and HFE molecules

Hematopoietic Stem Cell Transplantation

Contact Info

Product

Resources

About