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)

Hepatitis A virus (a picornavirus) and hepatitis E virus (so far unclassified) are small, non-enveloped and relatively stable RNA viruses with many similar, yet, not identical characteristics. Both viruses are transmitted preferentially by the fecal-oral route. Consequently, their spread is favoured by poor personal hygiene and inappropriate sanitary conditions. Infection can pass subclinically, take an acute and self limiting course, and can also manifest as fulminant hepatitis with liver failure. True chronic disease is unknown. Laboratory diagnosis is preferentially performed by serology, but can also be complemented by assay for viral RNA in stool or serum. Resolution of infection leads to immunity which, in the case of hepatitis A, is known to be fully protective and most likely lifelong. Available hepatitis A vaccines are able to induce a similar state of protection. Vaccines for hepatitis E are under development. Specific antiviral treatment is not yet available, neither for hepatitis A nor for hepatitis E.
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PMID:[Hepatitis A and E enterically transmitted virus infections of the liver]. 1545 63

Coxiella burnetii causes acute Q fever in humans and occasional chronic infections that typically manifest as endocarditis or hepatitis. Isolates associated with acute disease were found to be distinct from a group of chronic disease isolates by a variety of biochemical parameters and in a guinea pig fever model of acute disease, suggesting a difference in virulence potential. We compared antigenic polypeptides among C. burnetii isolates and found an immunodominant 28-kDa protein in acute group isolates but not in chronic group isolates (T. Ho, A. Hotta, G. Q. Zhang, S. V. Nguyen, M. Ogawa, T. Yamaguchi, H. Fukushi, and K. Hirai, Microbiol. Immunol. 42:81-85, 1998). In order to clone the adaA gene, the N-terminal amino acid sequence of adaA was determined and a 59-bp fragment was amplified from Nine Mile phase I DNA by PCR. The putative gene fragment was used to screen a lambda ZAP II genomic DNA library, and an open reading frame expressing a 28-kDa immunoreactive protein was identified. Sequence analysis predicted a gene encoding an approximately 28-kDa mature protein with a typical signal sequence. The adaA (acute disease antigen A) gene was detected in acute group C. burnetii isolates but not identified in chronic group isolates by PCR and Southern blotting. A typical signal peptide was predicted in adaA, and specific antibody to adaA reacted with the purified membrane fraction of acute group isolates by Western blotting, suggesting that adaA is exposed on the outer surface of C. burnetii. adaA was overexpressed in pET23a as a fusion protein in Escherichia coli to develop anti-recombinant adaA (anti-radaA) specific antibody, which recognized a approximately 28-kDa band in acute group isolates but not in chronic group isolates. In addition, immunoblotting indicates that radaA reacted with sera derived from animals infected with acute group isolates but did not react with sera from animals infected with chronic group isolates. These results support the idea that an adaA gene-targeted PCR assay and an radaA antigen-based serodiagnostic test may be useful for differential diagnosis of acute and chronic Q fever.
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PMID:Identification and characterization of an immunodominant 28-kilodalton Coxiella burnetii outer membrane protein specific to isolates associated with acute disease. 1573 Oct 54

CD8+ T cells are important for clearance of neurotropic mouse hepatitis virus (MHV) strain A59, although their possible role in A59-induced demyelination is not well understood. We developed an adoptive-transfer model to more clearly elucidate the role of virus-specific CD8+ T cells during the acute and chronic phases of infection with A59 that is described as follows. C57BL/6 mice were infected with a recombinant A59 virus expressing the gp33 epitope, an H-2Db-restricted CD8+ T-cell epitope encoded in the glycoprotein of lymphocytic choriomeningitis virus, as a fusion with the enhanced green fluorescent protein (RA59-gfp/gp33). P14 splenocytes (transgenic for a T-cell receptor specific for the gp33 epitope) were transferred at different times pre- and postinfection (p.i.). Adoptive transfer of P14 splenocytes 1 day prior to infection with RA59-gfp/gp33, but not control virus lacking the gp33 epitope, RA59-gfp, reduced weight loss and viral replication and spread in the brain and to the spinal cord. Furthermore, demyelination was significantly reduced compared to that in nonrecipients. However, when P14 cells were transferred on day 3 or 5 p.i., no difference in acute or chronic disease was observed compared to that in nonrecipients. Protection in mice receiving P14 splenocytes prior to infection correlated with a robust gp33-specific immune response that was not observed in mice receiving the later transfers. Thus, an early robust CD8+ T-cell response was necessary to reduce virus replication and spread, specifically to the spinal cord, which protected against demyelination in the chronic phase of the disease.
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PMID:Increased epitope-specific CD8+ T cells prevent murine coronavirus spread to the spinal cord and subsequent demyelination. 1573 Dec 31

Systemic amyloidosis frequently involves liver, however, clinically apparent liver disease is rare and, if observed, is usually mild. Rarely, primary amyloidosis may present with evidence of portal hypertension or hepatic failure. Although secondary amyloidosis may involve the liver and rarely causes liver pathologies such as cholestatic hepatitis and portal hypertension, to our knowledge, hepatic failure due to secondary amyloidosis has been reported once before. Herein, we presented a woman with subacute fulminant hepatic failure who had no known history of a chronic disease other than episodes of urinary tract infection, and secondary amyloidosis was diagnosed with post-mortem liver biopsy.
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PMID:Fulminant hepatic failure due to secondary amyloidosis. 1646 Oct 24

Lymphocyte infiltration into the central nervous system (CNS) following viral infection represents an important component of host defense and is required for control of viral replication. However, the mechanisms governing inflammation in response to viral infection of the CNS are not well understood. Following intracranial (i.c.) infection of susceptible mice with mouse hepatitis virus (MHV), mice develop an acute encephalomyelitis followed by a chronic demyelinating disease. The CXC chemokine ligand 10 (CXCL10) is expressed following MHV infection and signals T cells to migrate into the CNS. The functional contribution of the CXCL10 receptor CXCR3 in host defense and disease in response to MHV infection was evaluated. The majority of CD4+ and CD8+ T cells infiltrating the CNS following MHV infection express CXCR3. Administration of anti-CXCR3 antibody reduced CD4+ T cell infiltration (p<or=0.05), while CD8+ T cell trafficking was not affected. Anti-CXCR3 treatment during chronic disease correlated with improved motor skills and reduced demyelination. The selective effect of anti-CXCR3 treatment on CD4+ T cells was not the result of either reduced proliferation or modulation in chemokine receptor gene expression. Therefore, CXCR3 signaling has a non-redundant role in T cell subset trafficking in response to viral infection.
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PMID:Differential roles for CXCR3 in CD4+ and CD8+ T cell trafficking following viral infection of the CNS. 1647 46

The entity of non-A, non-B (NANB) hepatitis was identified in the early 1970's in the course of studies of transfusion-associated hepatitis. It was first thought to be a mild illness because most persons identified with acute hepatitis lacked symptoms, had mild enzyme elevations, and were not jaundiced. It was only after realisation that enzyme elevations persisted in almost all affected persons, and that about 20% of those undergoing liver biopsy showed fibrosis and even cirrhosis, that concern began to grow. This escalated further when it became clear that another potential outcome was evolution to hepatocellular carcinoma, a process that could take 20 to 40 years to develop. The discovery of the hepatitis C virus (HCV) in 1989 proved revolutionary, indicating that most (80% or more) of the NANB hepatitis cases were caused by this virus, and reinforcing the evidence that the majority of those acutely infected developed persistent chronic disease that could culminate in cirrhosis and even cancer. The first efforts to assess the natural history were retrospective studies that confirmed the long duration of infection, but identified a high rate of liver disease progression. Because they were conducted in tertiary care centers, the majority of patients that they studied already had potentially severe disease when first seen. Subsequent prospective studies described a more benign outcome, but most were of relatively short duration and therefore could not provide the needed long-term outcome information. Recently, a series of retrospective-prospective (non-concurrent prospective) studies involving transfusion recipients, children, women, and persons with community-acquired HCV infection suggest that evolution to cirrhosis is highly variable (2 to 20% at 20 years) and that progressive disease may be limited and not universal. Recent data suggest also that spontaneous recovery from infection may be higher than previously believed.
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PMID:Strategies for assessing the long-term consequences of Hepatitis C virus infection. 1650 39

Rheumatoid arthritis is the commonest form of inflammatory arthritis and affects about 1-3% of the population in the West and even more in the developing world due to the compounded factors of late detection and inadequate treatment in the overall background of poverty, deprivation, and improper macro and micronutrients in the diet in a sizeable segment of the population. Nearly 90% of patients with aggressive disease will become clinically disabled within 20 years. Furthermore, in patients with severe disease or extra-articular symptoms, mortality is equal to that for patients with triple artery coronary artery disease or Stage IV Hodgkin's lymphoma. Anemia is a very common comorbidity of rheumatoid arthritis. Anemia in rheumatoid arthritis is caused by various factors, for instance, cytokine impact of the advanced arthritic process on the host, or lack of proper nutrition and essential micronutrients in the diet, or coexistent helminthiasis, and/or impact of antiarthritic drugs on the host system, i.e., high steroid induced gastritis or ulcerations in gastric mucosa or subclinical or clinical hepatitis due to methotrexate or salazopyrin effects on bone marrow, only to name a few. Other pre-existing or compounding gastrointestinal problems, which alter the available iron stores or cause bone marrow dysfunction, may also help in adding to an anemic condition. If the anemia is 8 g/dl or less, blood transfusion or erythropoietin injection with adequate hematinic reserve is effective in normal situations, but is not that effective in anemia with a chronic disease background like rheumatoid arthritis. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypo antigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Seventy-eight units (42 ml -136 ml mean 80.6 ml +/- 3.6 ml SD, median 82.4 ml, mean packed cell volume 48.2 +/- 2.1 SD, mean percent hemoglobin concentration 16.4 g/dl +/- 1.5 g/dl SD) of placental umbilical cord whole blood was transfused (from 1 April 1999 to April 2005) after lower uterine cesarean section (LUCS) from consenting mothers to 28 informed consenting patients with advanced rheumatoid arthritis who had plasma hemoglobin of 8 g/dl or less. After collection, the blood was immediately transfused following the standard adult blood transfusion protocol. Each case was passed through the institutional ethical committee. The patients received two to six units of freshly collected placental umbilical cord blood without encountering any clinical, immunological or non-immunological reactions. Three days after completion of the transfusion of placental umbilical cord blood, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 2.03 to 23%, which returned to base level in most of the cases at the three-month CD34 re-estimation, without provoking any clinical graft vs host reaction in any of the patients.
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PMID:Placental umbilical cord whole blood transfusion to combat anemia in the background of advanced rheumatoid arthritis and emaciation and its potential role as immunoadjuvant therapy. 1676 35

Despite the absence of a natural reservoir for Q fever in the desert of Southern California, six cases have been identified during the past 32 years. During that period of time, two areas have been used by northern sheep ranchers from Idaho and Wyoming to import sheep to an area in the Coachella Valley through 1985. Thereafter, because of housing development, the sheep area was moved to Blythe along the Colorado River. All but two of these patients probably acquired infection by Coxiella burnetii by living or working in close proximity to these grazing areas but not directly involved with the sheep. The shift of infected patients from the Coachella Valley to Blythe (100 miles distant) seems to support that supposition. All patients with acute Q fever developed antibodies primarily to phase II antigen, whereas the only person with chronic Q fever developed phase I antibodies. All patients presented with granulomatous hepatitis. One also had a pulmonary infiltrate, and the single individual with chronic Q fever also had a mitral valve prosthesis, although echocardiography could not define endocarditis. All patients with acute infections responded to 3-5 weeks of therapy with doxycycline, whereas the patient with chronic disease failed 3 years of therapy with combination regimens. Further studies at the Eisenhower Medical Center on the prevalence of infection in Blythe, CA, and elsewhere are anticipated.
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PMID:Q fever in the Southern California desert: epidemiology, clinical presentation and treatment. 1683 4

The immune response to foreign or self antigens mediates liver damage during viral or autoimmune hepatitis. However, it now appears that also specific antigen-independent liver diseases, where liver damage has been attributed to occur from oxygen radical formation, seem to be mediated by cells of the innate and adaptive immune response. These liver disorders include alcoholic liver disease, non-alcoholic fatty liver disease or non-alcoholic steatohepatitis, and ischemia/reperfusion injury that impairs the function of liver grafts. Here it seems that breakdown of the gastrointestinal barrier might increase the concentration of bacterial toxins in the portal blood, which then activate cells of the innate immune system, e. g., Kupffer cells, but, depending on the nature of the toxin, probably also conventional T cells. Invariant NKT cells which specifically recognize glycolipid antigens were supposed to become activated during metabolic disorders related to obesity. However, both steatohepatitis as well as ischemia/reperfusion injury are associated with a Th1 cytokine response characterized by IFNgamma and TNFalpha elevation, that might reflect an NKT cell response on the one hand, but also conventional T lymphocytes, in particular CD4 (+) T cells, are critical for the pathophysiology of these disorders. In 1992 we described a model of T cell-dependent liver injury inducible by the T cell-mitogenic lectin concanavalin A. This model of immune-mediated liver injury was intensively used to study pathophysiological immune effector mechanisms as well as cytokine signaling important for hepatocellular apoptosis, inhibition of apoptosis and regeneration. Recently it became evident that the inflammatory response in this model is regulated by specific cytokine signals as well as by immune regulator cells. The immune-regulatory functions of the liver are of particular interest with respect to the scavenger function of this organ, being continuously exposed to foreign antigenic material from the gut which should be eliminated without causing chronic disease.
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PMID:Cellular and cytokine-mediated mechanisms of inflammation and its modulation in immune-mediated liver injury. 1723 22

Acute infection due to hepatitis C virus results in a chronic progression in 50-84% of cases. In the light of the risk of developing chronic disease and the response rate to treatment once the disease is established, it is very important to consider early treatment of acute hepatitis C before it progresses to the chronic form. The aim of this review is to evaluate the real efficacy and tolerance of Peg-interferon alpha-2b in monotherapy and in association with ribavirin in the treatment of patients affected by acute C hepatitis, to delineate the viral factors correlated with the sustained virological response and to consider when treatment should be started in relation to onset and what is the optimal duration of therapy. Also the pharmacodynamic and pharmacokinetic characteristics of PEG-IFN alpha-2b and ribavirin are reassessed. The analysis of literature demonstrates that Peg-interferon alpha-2b treatment is efficacious in terms of attaining sustained virological response (71-94% of cases). Treatment must be started within three months of onset and must be prolonged for three months. Only two studies have provided evidence the needed of a prolonged treatment for six months for genotype 1 infections. In all studies therapy has been generally well tolerated. Sustained virological response is independent of baseline viral load and of HCV genotypes in patients treated for six months, while in subjects treated for three months it seems to be dependent on HCV-genotype, with genotype 1 characterized by a less favourable outcome. Combination therapy with ribavirin does not seem to increase the response rate but could be proposed as a second choice to patients not responding to IFN monotherapy.
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PMID:PEG-interferon alpha-2b for acute hepatitis C: a review. 1769 45


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