Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review addresses three related bone marrow failure diseases, the study of which has generated important insights in hematopoiesis, red cell biology, and immune-mediated blood cell injury. In Section I, Dr. Young summarizes the current knowledge of acquired aplastic anemia. In most patients, an autoimmune mechanism has been inferred from positive responses to nontransplant therapies and laboratory data. Cytotoxic T cell attack, with production of type I cytokines, leads to hematopoietic stem cell destruction and ultimately pancytopenia; this underlying mechanism is similar to other human disorders of lymphocyte-mediated, tissue-specific organ destruction (diabetes, multiple sclerosis, uveitis, colitis, etc.). The antigen that incites disease is unknown in aplastic anemia as in other autoimmune diseases; post-hepatitis aplasia is an obvious target for virus discovery. Aplastic anemia can be effectively treated by either stem cell transplantation or immunosuppression. Results of recent trials with antilymphocyte globulins and high dose cyclophosphamide are reviewed. Dr. Abkowitz discusses the diagnosis and clinical approach to patients with acquired pure red cell aplasia, both secondary and idiopathic, in Section II. The pathophysiology of various PRCA syndromes including immunologic inhibition of red cell differentiation, viral infection (especially human parvovirus B19), and myelodysplasia are discussed. An animal model of PRCA (secondary to infection with feline leukemia virus [FeLV], subgroup C) is presented. Understanding the mechanisms by which erythropoiesis is impaired provides for insights into the process of normal red cell differentiation, as well as a rational strategy for patient management. Among the acquired cytopenias paroxysmal nocturnal hemoglobinuria (PNH) is relatively rare; however, it can pose formidable management problems. Since its first recognition as a disease, PNH has been correctly classified as a hemolytic anemia; however, the frequent co-existence of other cytopenias has hinted strongly at a more complex pathogenesis. In Section III, Dr. Luzzatto examines recent progress in this area, with special emphasis on the somatic mutations in the PIG-A gene and resulting phenotypes. Animal models of PNH and the association of PNH with bone marrow failure are also reviewed. Expansion of PNH clones must reflect somatic cell selection, probably as part of an autoimmune process. Outstanding issues in treatment are illustrated through clinical cases of PNH. Biologic inferences from PNH may be relevant to our understanding of more common marrow failure syndromes like myelodysplasia.
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PMID:New Insights into the Pathophysiology of Acquired Cytopenias. 1170 33

A 53-year-old man who had a history of fluminant hepatitis caused by precore mutant hepatitis B virus (HBV) was admitted to our hospital for the treatment of relapsed non-Hodgkin's lymphoma in July 2000. At admission, serum levels of aspartate aminotransferase and alanine aminotransferase were normal, but he tested positive for HBs antigen. The titer was 64-fold by radioimmunoassay. We initiated lamivudine at a daily dose of 75 mg to prevent HBV proliferation during chemotherapy. By September 2000, he had received six courses of rituximab at 375 mg/m(2) and four courses of fludarabine and mitoxantrone. No hepatic damage was observed from the initiation of treatment until March 2001. At present, four months after the completion of chemotherapy, he continues lamivudine, and the titer of HBs antigen is low at 4-fold. Rituximab is usually associated with mild toxicity, usually limited to infusion periods. The drug is not generally associated with increased incidence of opportunistic infections. However, some case reports have been recently published on severe viral infections following administration of rituximab. These include fluminant hepatitis caused by HBV, pure red cell aplasia due to parvovirus B19 and fatal varicella-zoster infection. While it remains unknown whether rituximab can be safely administered in patients with chronic HBV infection, this case report suggested that prophylactic administration of lamivudine is beneficial for suppressing reactivation of HBV during chemotherapy including rituximab. Rituximab should be used cautiously for patients with HBV infection, but prophylactic administration of lamivudine may be beneficial for preventing reactivation of HBV.
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PMID:Prophylaxis of hepatitis B reactivation using lamivudine in a patient receiving rituximab. 1175 21

We observed a 12-year-old boy with acute hepatitis and associated aplastic anemia (AA), where parvovirus B19 genome was repeatedly detected in liver and bone marrow biopsies, but not in blood samples. We conclude that: (1) B19 infection may be underdiagnosed as the causative agent responsible for acute hepatitis and associated AA if no organ-specific diagnostic tests are applied; (2) B19 deoxyribonucleic acid (DNA) can persist in the liver; (3) during the acute phase of hepatitis, extramedullary hematopoiesis may be involved in the susceptibility for hepatic B19 infection.
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PMID:Acute liver disease and aplastic anemia associated with the persistence of B19 DNA in liver and bone marrow. 1184 76

Parvovirus B19 is the causative agent of erythema infectiosum. In addition, the infection may be associated with other disease manifestations: anemia and aplastic crisis, thrombo- or granulocytopenies; spontaneous abortion or hydrops fetalis in pregnant women; acute and chronic arthritis in adults and children, myocarditis and hepatitis. Both acute and persistent courses of B19-infections have been reported. All patients develop IgG against the capsid proteins VP1 and VP2, the majority of virus neutralizing antibodies that offer life-long protection against reinfections are directed against the VP1-unique region. IgM is mainly directed against VP2-specific epitopes. These antibodies may be present for only a rather short period of two to ten weeks after acute infection. IgG-antibodies against the nonstructural protein NS1 are preferentially found in patients which are unable to eliminate the virus and develop persisting viremia or virus persistence in distinct organs, e.g. synovial fluid, liver, bone marrow.
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PMID:Antibody responses in parvovirus B19 infected patients. 1211 51

Infection of human parvovirus B19 (B19) is usually a self-limiting febrile illness, but can sometimes be life-threatening under certain circumstances, such as aplastic crisis in patients with haemolytic anaemia, hydrops fetalis in pregnant women and fulminant hepatitis. B19 can be transmitted through respiratory secretions, transplacentally and by transfusion of blood or blood products. In the present case, administration of intravenous immune globulin (i.v.Ig) transmitted B19 infection and consequently caused pure red cell aplasia and aggravation of hepatitis to fulminant hepatitis. Our case may raise important questions as to the safety of i.v.Ig and possible contamination by B19.
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PMID:Life-threatening human parvovirus B19 infection transmitted by intravenous immune globulin. 1278 11

The development of new technologies leads to the discovery of new viruses. For each of these new infectious agents, relevance to transfusion, including transmissibility by transfusion, pathogenicity, prevalence in blood donors, persistence and the availability of screening assays needs to be assessed. Since 1995, one virus and a new family of viruses have been identified. GB virus-C/hepatitis G virus (GBV-C/HGV), a flavi virus with some homology with and epidemiological features of HCV, is not related to post-transfusion hepatitis but seems to positively interfere with human immunodeficiency virus replication. Human circoviruses include TT virus (TTV) and SEN-V. Both are highly variable, constituting a large family of distantly related viruses. They appear ubiquitous, infecting humans very early in life and are largely persistent. No clinical symptoms or pathogenicity is associated with TTV, but SEN-V might be associated with some non-A-E post-transfusion hepatitis. Parvovirus B19 has been known for many years, but its transmission to recipients of plasma derivatives despite viral inactivation raised the issue of screening plasma pools by nucleic acid testing. Most fractionators quantify B19 DNA in plasma pools to ensure a viral load of <10(4) IU mL-1.
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PMID:Nucleic acid testing for emerging viral infections. 1222 Feb 57

The reconstitution of blood and its components is hampered by factors of compatibility, availability, and the risk of transmission of infectious diseases. Protozoal agents such as plasmodium malariae and trypanosoma cruzi are only regionally relevant. Bacterial transmissions are easy to prevent and treat. Antibody, antigen, and nucleic acid screening have been implemented to prevent transmission of blood-borne viruses. Transfusion-relevant viruses include hepatitis B and C virus (HBV and HCV), human immunodeficiency virus (HIV), human T leukemia virus (HTLV-I), and in certain circumstances, parvovirus B19, hepatitis A virus (HAV), and cytomegalovirus (CMV). Of great concern is the possible transmission of prion protein causing transmissible spongiform encephalopathy. Of future interest will be whether other viruses such as Nipah and Hendra virus are blood-borne and whether viruses such as TT, SEN, and GBV-C are involved in diseases or their progression, while not causing hepatitis.
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PMID:Virus safety of human blood, plasma, and derived products. 1237 92

Fresh frozen plasma (FFP) contains higher levels of intact coagulation factors and coagulation and fibrinolysis inhibitors than solvent/detergent-treated plasma (SD plasma), and also greater residual cell contamination. SD plasma is a particle-free plasma of uniform quality. SD treatment, however, has the specific result of reducing the activities of some inhibitors. Both plasma types carry a minimal residual risk of transmitting human immunodeficiency virus (HIV)-1/2, hepatitis virus B (HBV), and hepatitis virus C (HCV), but SDP is, in addition, also safe with respect to other lipid-enveloped viruses and perhaps with respect to hepatitis virus A (HAV), also due to its antibody (Ab) content. Future revisions of therapeutic plasma safety and quality standards should consider the following points:For FFP:reduce residual cell count in all FFP units to values below 5 x 10(6) leukocytes/l;screen donors for Parvovirus B19 genome and antibodies in order to establish a sufficiently large collection of genome-negative and antibody-positive donors whose FFP can be used for selected patients;For SDP:introduce pool testing for Parvovirus B19 genome; fix an upper limit for genome and a lower limit for antibody content;in addition to the standard quality control methods for therapeutic plasma, focus on assays to test for functionally intact proteinase inhibitors such as alpha(2)antiplasmin (alpha(2)AP) and alpha(1)proteinase inhibitor (alpha(1)PI) that are important for plasma indications. Commercially available kits may not be sufficient to show changes in inhibition kinetics. For both types:introduce an activation marker such as thrombin-antithrombin complex (TAT) as a random test to monitor activation processes during withdrawal, separation, manufacturing, and storage;abolish inappropriate parameters like Antithrombin III (AT III) and coagulation factor XI that are not relevant for changes in plasma quality;finally, support every effort towards establishing an efficient documentation and reporting system on efficacy and side effects of plasma transfusions. Effective reporting alone might help to reveal deficiencies of specific plasma quality and to overcome them through modifications to manufacturing processes and testing, or by defining its indications more precisely.
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PMID:Quality of therapeutic plasma-requirements for marketing authorization. 1237 93

In an effort to determine the cause of non-A-E hepatitis, a retrospective study was undertaken on a group of patients with hepatitis but without serological infection markers of hepatitis viruses A-E. A total of 60 patients admitted to Beijing Ditan Hospital during the period of September 1997 and September 1999 were chosen for this study. These patients were diagnosed as either acute or chronic hepatitis, but no serological markers of hepatitis viruses A-E were detected. Since TT virus (TTV), human parvovirus B19 (B19), SEN virus (SENV), and GB virus C/HGV were reported to be associated with hepatitis, attempts were made to detect the presence of these viruses in the sera of patients with non-A-E hepatitis by a nested polymerase chain reaction (nPCR) method. Also, more sensitive nPCR and RT-nPCR methods were used to determine HBV DNA and HCV RNA in these patients. Results derived from these analyses demonstrate that HBV DNA was detected in most of these patients (47/60, 78.3%), suggesting that HBV infection played a major role in occult non-A-E hepatitis and detection of HBV DNA by more sensitive PCR methods such as nPCR should be considered for diagnosis of HBV infection. In addition, HCV RNA was detected in three (5%) of these patients. However, GBV-C (HGV) RNA was not detected, and TTV, B19, and SENV appear not to be associated with non-A-E hepatitis, as the prevalence rates of these viruses in patients with non-A-E hepatitis were similar to those in patients with viral hepatitis A-E. The results from this study indicate that co-infection of TTV or B19 with HBV did not increase the severity of the disease.
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PMID:Retrospective analysis of non-A-E hepatitis: possible role of hepatitis B and C virus infection. 1243 78

Erythrovirus B19 (B19) previously called parvovirus B19 is the only human pathogen in the family Parvoviridae. B19 is an autonomously replicating small single stranded non-enveloped DNA of 5.5 Kb with hairpin termini through which it replicates, when the cells are in the S-phase. Virus host interactions are mediated through the capsid protein VP2 attaching to P antigen receptor expressed on certain host cells, which imparts narrow host and tissue tropism. It affects the progenitor red cells, megakaryoblast, endothelial cells and a few organs like the kidney and the heart. VP1 antibodies are neutralizing, non-structural protein NS-1 exert cell cytotoxicity while NS-2 regulates replication. The virus is present world-wide. Most infections are asymptomatic but individuals with red cell defect, immune system defects or immunosuppression manifest disease, which may be persistent. In the immunocompetent host it causes erythema infectiosum in children, arthralgia or chronic polyarthritis especially in females, nonimmune hydrops foetalis, several haematological disorders and recently fulminant hepatitis in children. The virus is transmitted through the upper respiratory tract by droplets, transfusion of blood or its components (factor VIII) and transplacentally. The incubation period is 6-11 days after intranasal inoculation, in human volunteers. Detection of IgM antibodies is most important in serological diagnosis. Viral DNA can be detected by polymerase chain reaction (PCR) or hybridization procedures in patients sera or infected tissues. Intravenous immunoglobulin can be used in the treatment as well as in prophylaxis. In view of its increasing association with a wide variety of clinical diseases, a closer look in its biology, host virus interactions and evaluation of VP1 and VP2 recombinant proteins as B19 vaccines are areas which need the urgent attention of parvovirologists, epidemiologists and clinicians.
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PMID:Erythrovirus B19 infection in humans. 1245 23


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