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)

Most cases of hepatitis C virus (HCV) infection result in chronic disease; however, a very small fraction of patients naturally clear the virus and resolve chronic hepatitis. In an attempt to correlate immune response with chronic disease resolution, we compared the antibody response in patients with different outcomes of the infection. Antibody responses to HCV structural proteins were assessed in 34 patients originally diagnosed with acute hepatitis. Five cases resolved acute infection, 22 developed chronic hepatitis, and 7 naturally resolved chronic hepatitis C. To estimate HCV neutralizing antibodies we used the neutralization of binding (NOB) assay, which evaluates inhibition of the envelope-2 protein binding to human cells. Enzyme-linked immunosorbent assay was used for the quantitative assessment of serum antibodies. The presence of HCV RNA was ascertained by reverse transcription-polymerase chain reaction. In 6 of 7 patients naturally recovered from chronic hepatitis C, the emergence and the persistence (for more than 3 months) of high serum titers (>1/600) of NOB antibodies coincided with virus clearance and clinical resolution of hepatitis. NOB antibody activity was observed in only 2 of 5 patients recovered from acute hepatitis C. Chronic patients who did not show any resolution during the course of the study developed low or no NOB antibodies. Because of the correlation between prolonged high NOB titers and natural resolution of chronic hepatitis C, vaccination or passive immunization aimed at high titers of NOB antibodies may be valuable new therapeutic approaches for chronic hepatitis C.
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PMID:High titers of antibodies inhibiting the binding of envelope to human cells correlate with natural resolution of chronic hepatitis C. 975 51

Chronic disease conditions that are associated with elevated proliferation are well established as risk factors for cancer development. These may be due to viruses (for example, in the case of hepatitis and liver cancer), bacterial infections, parasite infestation or physical trauma. In addition to these exogenous agents there are also metabolic abnormalities that can contribute, caused by genetic or epigenetic influence. In the latter case, an increase in serum levels of the hormones oestrogen, testosterone and insulin may be of special importance. The present review concentrates attention on factors that induce elevated cell turnover and for which there is epidemiological and/or experimental evidence of a link with neoplasia, with particular stress on the individual organ or tissue level.
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PMID:Chronically elevated proliferation as a risk factor for neoplasia. 988 83

Q fever is a zoonosis with a worldwide distribution with the exception of New Zealand. The disease is caused by Coxiella burnetii, a strictly intracellular, gram-negative bacterium. Many species of mammals, birds, and ticks are reservoirs of C. burnetii in nature. C. burnetii infection is most often latent in animals, with persistent shedding of bacteria into the environment. However, in females intermittent high-level shedding occurs at the time of parturition, with millions of bacteria being released per gram of placenta. Humans are usually infected by contaminated aerosols from domestic animals, particularly after contact with parturient females and their birth products. Although often asymptomatic, Q fever may manifest in humans as an acute disease (mainly as a self-limited febrile illness, pneumonia, or hepatitis) or as a chronic disease (mainly endocarditis), especially in patients with previous valvulopathy and to a lesser extent in immunocompromised hosts and in pregnant women. Specific diagnosis of Q fever remains based upon serology. Immunoglobulin M (IgM) and IgG antiphase II antibodies are detected 2 to 3 weeks after infection with C. burnetii, whereas the presence of IgG antiphase I C. burnetii antibodies at titers of >/=1:800 by microimmunofluorescence is indicative of chronic Q fever. The tetracyclines are still considered the mainstay of antibiotic therapy of acute Q fever, whereas antibiotic combinations administered over prolonged periods are necessary to prevent relapses in Q fever endocarditis patients. Although the protective role of Q fever vaccination with whole-cell extracts has been established, the population which should be primarily vaccinated remains to be clearly identified. Vaccination should probably be considered in the population at high risk for Q fever endocarditis.
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PMID:Q fever. 1051 1

Hepatitis C virus (HCV) was unambiguously identified in the year 1989 as the agent responsible for most cases of non-A, non-B hepatitis, a chronic disease that often leads to cirrhosis and hepatocellular carcinoma. Having developed the means to detect the virus in the general population, it is now apparent that HCV infection is widespread and is likely to remain a health threat unless effective treatments are developed. The inability to propagate the virus in tissue culture and the scarcity of convenient animal models have proved to be major obstacles in drug discovery. Despite these limitations, several opportunities exist for targeted drug development based on the viral enzymes that have been characterized so far. These targets and inhibitors reported to be active against them are discussed in the following review.
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PMID:Hepatitis C virus: an overview of current approaches and progress. 1052 69

Variant viruses mutated in the immunodominant cytotoxic T cell epitope surface (S) glycoprotein S-510-518 are selected in mice chronically infected with mouse hepatitis virus, strain JHM. We determined whether this selection occurred in the presence of an oligoclonal or polyclonal T cell response using soluble MHC/peptide tetramers in direct ex vivo analyses of CNS-derived lymphocytes. A total of 42% (range, 29-60%) of CD8 T cells in the CNS of mice with acute encephalitis recognized epitope S-510-518. A total of 34% (range, 18-62%) of cells from mice with hind limb paralysis (and chronic demyelination) were also epitope specific, even though only virus expressing mutated epitope is detected in these animals. Sequence analysis of the beta-chain CDR3 of 487 tetramer S-510-518-positive cDNA clones from nine mice showed that a majority of clonotypes were identified in more than one mouse. From these analyses, we estimated that 300-500 different CD8 T cell clonotypes responsive to epitope S-510-518 were present in each acutely infected brain, while 100-900 were present in the CNS of each mouse with chronic disease. In conclusion, a polyclonal CD8 T cell response to an epitope does not preclude the selection of T cell escape mutants, and epitope-specific T cells are still present at high levels even after RNA-encoding wild-type sequence is no longer detectable.
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PMID:Selection of CTL escape mutants in mice infected with a neurotropic coronavirus: quantitative estimate of TCR diversity in the infected central nervous system. 1057 Mar

Known since the beginning of the first millenium, the hemophilias are among the most frequent inherited disorders of blood coagulation and definitely the most severe. In the 1970s, with the availability of concentrated preparations of the deficient coagulation factors VIII and IX and with the large-scale adoption of home treatment, hemophilia care became one of the most gratifying examples of successful secondary prevention of a chronic disease. Unfortunately, in the early 1980s It was recognized that factor concentrates prepared from plasma pooled from thousands of donors transmitted the hepatitis and the human immunodeficiency viruses. The scientific community reacted promptly to the devastation brought about by hepatitis and AIDS. The last 15 years of the second millenium have witnessed the development of methods that applied during concentrate manufacturing inactivate viruses escaping the screening procedures. The adoption of these measures has reduced dramatically the risk of transmission of bloodborne infections. The production of recombinant factors and their availability for patient treatment epitomize progress in hemophilia care through DNA technology. Methods based on the polymerase chain reaction (PCR) have unraveled an array of gene lesions associated with hemophilia, permitting improved secondary control of the disease through carrier detection in women from affected families and prenatal termination of their affected male infants. This article will review the aforementioned areas of progress and discuss unresolved problems (such as treatment of patients with antibodies, the risk of new infectious complications, and the issue of secondary tumors). Hopes and expectations for further improvement in the third millenium and particularly the prospects of hemophilia cure through gene replacement therapy will also be mentioned.
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PMID:The hemophilias: progress and problems. 1059 59

GB virus C (GBV-C) RNA positivity rates were examined in serum specimens from 231 patients with liver disease (23 patients with hepatitis B, 175 patients with hepatitis C, five patients with hepatitis B virus plus hepatitis C virus coinfection, and 28 patients with non-A, non-B, non-C hepatitis) to clarify the clinical significance of this virus. GBV-C RNA was detected in none of 12 patients with fulminant hepatitis, one of two patients with acute hepatitis positive for hepatitis B surface antigen and one of four patients with acute non-A, non-B, non-C hepatitis. Pathogenetic involvement of GBV-C was suspected in some patients in the latter group. Among patients with the non-B, non-C type of chronic disease, one of seven with cirrhosis (14%) and none with chronic hepatitis or hepatocellular carcinoma were GBV-C-positive. In chronic hepatitis C patients who had received interferon treatment, no difference was found in clinical findings, alanine aminotransferase (ALT) concentrations, histology or response to interferon between 11 patients who were GBV-C RNA-positive and 101 patients who were GBV-C RNA-negative. Moreover, changes in ALT after interferon therapy showed no relation to positivity for GBV-C RNA. On the basis of these findings, GBV-C appears to be an unlikely cause of initiation or progression of chronic hepatic diseases.
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PMID:GB virus C infection: clinical significance. 1062 21

Six different hepatitis viruses have now been characterized. Hepatitis B and C are the two hepatitis infections that are of greatest concern for surgeons. Hepatitis B and C share several features that have led to this concern. Both are blood-borne infections. Both are associated with chronic infection ultimately leading to cirrhosis, portal hypertension, and hepatocellular carcinoma, and both can be occupational infections for the surgeon after percutaneous injury associated with infected blood. Chronic hepatitis B infection is seen in 1.25 million people in the U.S. It is associated with a transmission rate to healthcare workers of 25 to 30 per cent following a hollow needle stick injury. Five per cent of acute infections result in chronic disease. It can be effectively prevented as an occupational infection by vaccination with the highly effective hepatitis B vaccine. Chronic hepatitis C infection is present in nearly 4 million people in the U.S. It has a lower rate of transmission than hepatitis B following needle stick injury, but it has a 50 to 80 per cent rate of chronic disease after acute infections. There is no vaccine for hepatitis C, and only prevention of blood exposure will avoid the risks of this occupational infection. Other hepatitis viruses are likely to be identified. Prevention of blood exposure, by the better use of barriers in the operating room and modification of surgical techniques, is recommended to prevent occupational infection from both known and unknown blood-borne viruses from the surgical patient.
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PMID:Hepatitis: risks for the surgeon. 1069 49

Autoimmune hepatitis can present as either acute or chronic disease in children. Clinical and laboratory features, including association with extrahepatic autoimmune syndromes and prompt response to immunosuppressive treatment, circulating autoantibodies and hypergammaglobulinemia, suggest an immune etiology. However, the disease mechanism remains uncertain. Different types of autoimmune hepatitis are defined on the basis of which autoantibodies are present: anti-smooth muscle (type 1), anti-liver/kidney microsomal (type 2), or anti-soluble liver antigen (type 3). Diseases which may be clinically similar to autoimmune hepatitis must be excluded before the diagnosis of autoimmune hepatitis is established: Wilson's disease, primary sclerosing cholangitis, chronic hepatitis B or C, and drug-induced liver disease are among the most important entities. Corticosteroids alone or with azathioprine constitute the usual treatment for autoimmune hepatitis. Although some children achieve a complete remission, or even recovery, and can stop immunosuppressive treatment, others required low-dose prednisone treatment indefinitely.
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PMID:Autoimmune hepatitis. 1082 19

Publications about liver transplantation (LTX) for autoimmune hepatitis (AIH) have started to emerge, but many issues remain unresolved. We reviewed data on 32 patients transplanted for AIH to determine how pretransplantation and posttransplantation characteristics correlate with recipient outcome, including disease recurrence. Recipients were 37+/- 14 years old; 30 of 32 were women. Most had chronic disease (8 +/- 6 years); 25% had fulminant failure. The majority had ascites (91%), jaundice (88%), elevated prothrombin time (18 +/- 3 seconds), and hypoalbuminemia (2.7 +/- 0.6 g/dL). All had hypergammaglobulinemia (3.0 +/- 1.0 g/dL) and autoantibodies (72% antinuclear, 74% smooth muscle). Only one was HLA A1-B8-DR3 positive. Other autoimmune disorders affected 25% of patients; half improved after transplantation. Actuarial survival was 81% at 1 and 2 years posttransplantation. There was a high frequency of rejection (75% of recipients had 1.7 +/- 0.8 episodes), and 39% of rejections required OKT3. Among 24 recipients with long-term follow-up (27 +/- 14 months), histologically proven recurrent AIH occurred in 25%, 15 +/- 2 months posttransplantation; half (3 patients) required retransplantation 11 +/- 3 months after diagnosis. After retransplantation 2 of 3 patients had re-recurrence within 3 months; 1 received a third LTx. Recurrence occurred in 6 of 18 patients transplanted for chronic disease vs. 0 of 6 transplanted as fulminants (P = not significant [NS]). Patients with and without recurrence had similar rejection profiles. In summary, results of LTx for AIH are excellent. However, AIH patients have a high frequency of rejection and often require OKT3. Furthermore, severe recurrent AIH sometimes develops, particularly in chronic versus fulminant AIH patients and in those already retransplanted for recurrence. Multicenter studies could elucidate the best posttransplantation immunosuppressive regimens for AIH patients.
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PMID:Liver transplantation for autoimmune hepatitis. 1100 37


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