Cases reported "Hepatitis, Viral, Human"

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1/26. Analysis of immune cells in a patient with post-transfusion hepatitis caused by human cytomegalovirus.

    Cellular immune responses are associated with the pathogenesis of human cytomegalovirus (HCMV) hepatitis. We investigated a patient with post-transfusion HCMV hepatitis. A 9 year-old girl was involved in a traffic accident and suffered from traumatic damage to the left kidney and diaphragm and received a pelvic bone fracture. At emergency surgery she was transfused with 1200 ml of fresh whole donor blood. Abnormal liver function was observed in the 10 days after surgery. Titers of serum anti-HCMV IgG and IgM antibodies were elevated at 11, 17 and 25 weeks after operation. We analyzed the surface markers of peripheral blood mononuclear cells obtained 21 weeks after surgery. The CD4/CD8 ratio and the number of CD16 CD56 decreased. We detected HCMV immediate early (IE) dna in the fractionated peripheral blood cells (polymorphonuclear leukocytes, CD2 , CD4 and CD8 T lymphocytes) by polymerase chain reaction. The histology of liver biopsy at 23 weeks after operation showed the findings of acute hepatitis and the absence of HCMV IE antigen. It was considered that the immunosuppressive condition associated with the trauma, operation or transfusion itself induced the reactivation of HCMV or that transfused blood cells infected with HCMV caused reinfection. It was also speculated that HCMV hepatitis was not only due to the direct damage of hepatic cells by HCMV, but also due to the cellular immune responses associated with HCMV infection.
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2/26. Detection of human parvovirus B19 in a patient with hepatitis.

    parvovirus B19 has been associated by some investigators with cases of severe hepatitis. The aim of the present study was to determine the presence of active parvovirus B19 infection among 129 Brazilian patients with non-A-E hepatitis. The patients were assayed for antibodies against parvovirus B19, IgM class, by ELISA. In IgM-positive cases, parvovirus B19 dna was assayed by PCR in serum and liver tissue and parvovirus VP1 antigen in liver tissue was assayed by immunohistochemistry. Antibodies against parvovirus B19, IgM class, were detected in 3 (2.3%) of 129 patients with non-A-E hepatitis. Previous surgery and blood transfusions were reported by these 3 patients. One patient was a 56-year-old female with severe hepatitis, with antimitochondrial antibody seropositivity and submassive necrosis at liver biopsy, who responded to corticosteroid therapy. Strong evidence for active parvovirus B19 infection was found in this patient, with parvovirus B19 dna being detected by PCR in liver tissue. Furthermore, parvovirus VP1 antigen was also detected in liver tissue by immunohistochemistry. The other two IgM-positive patients were chronic hepatitis cases, but active infection was not proven, since neither viral dna nor antigen were detected in their liver tissues. This and other reports suggest a possible relation between parvovirus B19 infection and some cases of hepatitis.
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3/26. SARS-associated viral hepatitis caused by a novel coronavirus: report of three cases.

    Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the world health organization case definition of probable SARS and developed marked elevation of alanine aminotransferase were included. Percutaneous liver biopsies were performed. Liver specimens were examined by light and electron microscopy, and immunohistochemistry. Reverse-transcriptase polymerase chain reaction (RT-PCR) using enhanced real-time PCR was applied to look for evidence of SARS-associated coronavirus infection. Marked accumulation of cells in mitosis was observed in two patients and apoptosis was observed in all three patients. Other common pathologic features included ballooning of hepatocytes and mild to moderate lobular lymphocytic infiltration. No eosinophilic infiltration, granuloma, cholestasis, fibrosis, or fibrin deposition was noted. Immunohistochemical studies revealed 0.5% to 11.4% of nuclei were positive for proliferative antigen Ki-67. RT-PCR showed evidence of SARS-associated coronavirus in the liver tissues, but not in the sera of all 3 patients. However, electron microscopy could not identify viral particles. No giant mitochondria, micro- or macro-vesicular steatosis was observed. In conclusion, hepatic impairment in patients with SARS is due to SARS-associated coronavirus infection of the liver. The prominence of mitotic activity of hepatocytes is unique and may be due to a hyperproliferative state with or without disruption of cell cycle by the coronavirus. With better knowledge of pathogenesis, specific therapy may be targeted to reduce viral replication and modify the disease course.
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4/26. Syncytial giant-cell hepatitis. Sporadic hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features.

    BACKGROUND AND methods. We describe a new form of hepatitis, occurring in 10 patients over a period of six years, characterized clinically by manifestations of severe hepatitis, histologically by large syncytial giant hepatocytes, and ultrastructurally by intracytoplasmic structures consistent with paramyxoviral nucleocapsids. RESULTS. The patients ranged in age from 5 months to 41 years. The tentative clinical diagnosis before biopsy was non-A, non-B hepatitis in five patients and autoimmune chronic active hepatitis in the others. Five patients underwent liver transplantation; the others died. The diagnosis of syncytial giant-cell hepatitis was established pathologically. The liver cords were replaced in all 10 patients by syncytial giant cells with up to 30 nuclei. In 8 of the 10 the cytoplasm contained pleomorphic particles of 150 to 250 microns, filamentous strands, and particles of 14 to 17 nm with peripherally disposed spikes resembling paramyxoviral nucleocapsids. Structures resembling degenerated forms were found in the other two patients. One of two chimpanzees injected with a liver homogenate from the index patient had an increase in the titer of paramyxoviral antibodies, probably an anamnestic reaction to previous paramyxoviral infection, suggesting that a paramyxoviral antigen but not viable virus was present in the liver homogenate. CONCLUSIONS. Although further virologic studies will be required for precise classification, we believe that paramyxoviruses should be considered in patients with severe sporadic hepatitis.
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5/26. Clustering of different subtypes of hepatitis B surface antigen in families of patients with chronic liver diseases.

    Clustering of hepatitis B surface antigen (HBsAg) with both subtypes adr and adw in three families of patients with chronic liver diseases or hepatocellular carcinoma was demonstrated in taiwan where adw is the main subtype. The subtype in the children was similar to that in their mothers, suggesting maternal transmission. In all the family units clustered with different subtypes, the same pattern occurred, invariably with fathers carrying HBsAg/adr and the children carrying HBsAg/adw. The subtype difference clearly rules out the transmission of hepatitis b virus (HBV) from father. Horizontal infection with the locally dominant adw-subtyped HBV in the children of fathers carrying HBsAg/adr explains the discrepancy of the subtypes in these families. Clustering of two HBsAg-positive brothers with hepatocellular carcinoma in one of the families was found. That both adr-subtyped and adw-subtyped HBV are capable of inducing chronic active hepatitis in another family suggests that host factors are probably more important in determining the clinical course of HBV infection.
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6/26. Simultaneous primary infection with HIV and CMV leading to severe pancytopenia, hepatitis, nephritis, perimyocarditis, myositis, and alopecia totalis.

    Simultaneous primary infection with HIV and CMV in an 18-year-old woman led to an acute cytotoxic reaction, manifesting as pancytopenia, hepatitis, nephritis, perimyocarditis, and myositis. Within 14 days parameters indicating acute cell damage reverted to normal. Two weeks later transient alopecia totalis developed. Initially, HIV-antigen but no hiv antibodies were present. Within 3 weeks HIV-IgG antibodies appeared while HIV antigen disappeared. Anti-CMV-IgM was clearly and anti-CMV-IgG questionably positive; IgM persisted further, while IgG remained definitely undetectable. We speculate that a particular HIV-induced imbalance of the immune system led to a generalized severe cytotoxic reaction to a simultaneous infection with CMV.
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7/26. Immunohistologic identification of Epstein-Barr virus-induced hepatitis reactivation after OKT-3 therapy following orthotopic liver transplant.

    Reactivated Epstein-Barr virus infection associated with hepatitis appeared in a liver transplant patient receiving monoclonal OKT-3 antibody for rejection. The histologic findings in liver biopsy specimens characteristic of allograft rejection were observed prior to and during the initial phase of antirejection therapy. However, failure of a complete response to antirejection therapy promoted rebiopsy. The specimen showed portal infiltrates composed predominantly of plasma cells and immunoblasts. The presumptive diagnosis of Epstein-Barr virus hepatitis was confirmed by staining frozen liver tissue for Epstein-Barr virus nuclear-associated antigen. OKT-3 therapy was discontinued, and cyclosporine and steroid doses were reduced. Gradually, clinical features, serum aminotransferase and bilirubin levels, and the portal lymphoid infiltrate resolved. Epstein-Barr virus serology showed an increase in convalescent titers IgG-antiviral capsid antigen, and Epstein-Barr virus nuclear-associated antigen. The histologic, clinical, and laboratory features supporting the diagnosis of Epstein-Barr virus hepatitis in a liver transplant patient are presented and discussed. This diagnosis guided appropriate therapy.
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8/26. Impaired fibrin polymerization in viral hepatitis. Report of a case: probable identity of the inhibitor with beta2-microglobulin.

    A case is described in which a patient developed TT prolongation and bleeding during CMV hepatitis following successful renal transplantation. Bence-Jones proteinuria was noted, but there was no other evidence of myeloma. Bence-Jones proteinuria, TT prolongation, and bleeding abated as hepatitis resolved. in vitro, a protein isolated from the patient's urine was capable of prolonging the TT markedly, but it did not impair thrombin esterase activity. The effect of the protein seemed to be inhibition of fibrin polymerization. Sephadex gel filtration revealed a single TT-prolonging peak at 11,000 daltons, containing kappa, lambda, and delta antigens. By radioimmunoassay, virtually all the protein present reacted as beta2-microglobulin. Incubation with anti-beta2-microglobulin antiserum markedly attenuated anticoagulant activity. The paraprotein observed transiently in this patient's urine during hepatitis had potent anticoagulant activity and may well have accounted for his abnormal TT and bleeding diathesis; this paraprotein was not distinguishable from beta2-microglobulin.
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9/26. Disseminated herpes simplex virus infection in an apparently immunocompetent woman.

    A young, previously healthy woman developed bilateral exudative tonsillitis that was associated with severe systemic symptoms. This was followed by evidence of multisystem disease with acute abdominal pain, raised liver enzyme levels, respiratory difficulty, increasing drowsiness and multiple vesicular skin lesions. herpes simplex virus type-1 was isolated from skin lesions and a throat swab and herpes simplex virus type-1 antigen was detected in a liver biopsy sample. She recovered rapidly without any sequelae after treatment with intravenously administered acyclovir.
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10/26. Adenovirus hepatitis in a patient with severe combined immunodeficiency.

    An autopsy case of adenovirus hepatitis with severe combined immunodeficiency (SCID) is presented. A 7-month-old female was admitted to the Kitasato University Hospital with chief complaint of persistent fever. A diagnosis of severe combined immunodeficiency (SCID) was made because of defective function in both T and B lymphocytes. Respiratory disturbance and severe hepatic dysfunction were manifested after admission. She died of respiratory failure on the 40th hospital day. autopsy findings revealed many focal necroses scattered irregularly throughout the liver. Degenerating hepatocytes around the focal necrosis contained nuclear inclusion bodies, and crystalline arrays of adenovirus virions were recognized in these cells by electron microscopy. Adenovirus antigens were brilliantly detected in the nuclear inclusion bodies by indirect immunofluorescence.
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