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)

A 14-year-old girl with acute lymphoblastic leukemia in second remission received an allogeneic marrow graft from her HLA identical brother. Cyclosporine A and short term methotrexate were given for prophylaxis against graft versus host disease. On day 42 post transplantation elevation of SGOT and SGPT was recognized, rising the next day to 8,560IU and 2,590IU, respectively. Prothrombin activity dropped below 10%. HCV antibody and HBs antigen were both negative. Fulminant hepatitis was diagnosed, therefore plasma exchange was initiated. However, hepatic encephalopathy developed and she died on day 57. The postmortem liver appearance was consistent with early changes of veno-occlusive disease. Such atypical cases of VOD with late onset are difficult to distinguish from fulminant hepatitis but should be kept in mind.
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PMID:[Fulminant hepatitis-like veno-occlusive disease of the liver after allogeneic bone marrow transplantation in acute lymphoblastic leukemia]. 831 37

HLA-A, B, C and DR locus specificities studied in 168 patients (71 Chronic active Hepatitis, 97 Chronic Persistent Hepatitis) serologically and histopathologically proven Chronic Hepatitis B Virus infection. There were 113 men and 55 women with a mean age of 23.2 (21-52) years. Hundred and seventy four healthy subjects (107 men, 67 women) included in control group with a mean age of 26.4 (20-54) years. The frequency of HLA A3 (p < 0.01), HLA A11 (p < 0.01), HLA B35 (p < 0.05) and HLA B51 (p < 0.01) were significantly higher in patients than in healthy control subjects. Comparisons among the other HLA-A, B, C and DR locus were found to be statistically non-significant.
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PMID:[Relationship of histocompatibility groups to chronic HBV infections]. 836 14

GM-CSF has been used successfully in autologous BMTs, and more recently in patients undergoing allogeneic BMT, for acute or chronic leukemia. We report two patients with hepatitis-related aplastic anemia who received recombinant human GM-CSF following HLA-identical sibling allogeneic BMTs. Both patients were conditioned with CY 200 mg/kg given over 4 days and received GM-CSF at 250 micrograms/m2 beginning 6 h after marrow infusion and continuing daily until the absolute neutrophil count was > 1.0 x 10(9)/l for 2 days. Both patients had prompt engraftment, achieving an absolute neutrophil count of > 0.5 x 10(9)/l on day 13. Neither patient had side-effects attributable to the GM-CSF although one patient developed severe acute GVHD after the cessation of GM-CSF therapy. Our experience suggests that GM-CSF can be safely used in aplastic anemia patients undergoing BMT and that GM-CSF may be useful to decrease the incidence of graft failure associated with less intensive conditioning regimens.
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PMID:Use of recombinant GM-CSF following allogeneic BMTs for aplastic anemia. 840 68

The pathogenic mechanisms underlying the development of autoimmune hepatitis (AIH) are still unclear. Since AIH is associated with the presence of various autoantibodies and certain HLA subtypes, it is likely that T and B cells play a major role in this disease. In this study we have determined the functional capacities of in vivo preactivated liver-infiltrating T cells (LTC) from patients with AIH. As controls we used LTC from patients with non-autoimmune hepatitis (non-AIH). Our results show that preactivated LTC from patients with AIH predominantly (190/255 clones) reside in the CD4+ population, whereas LTC in non-AIH are dominated by the CD8+ phenotype (148/254 clones). In view of this finding we have investigated the cytokine secretion patterns of 102 randomly chosen CD4+ T cell clones from six patients with AIH. As controls we have used 58 CD4+ LTC from 11 patients with non-AIH. All clones were stimulated by lectin and irradiated accessory cells and subsequent cytokine production was evaluated. LTC from patients with AIH have a lower interferon-gamma (IFN-gamma)/IL-4 ratio compared with LTC from non-AIH. Although clones from some patients with AIH produced very high amounts of IL-4 in vitro, this was not a constant finding. These results show that in vivo preactivated LTC from patients with AIH are mostly CD4+ T cells that produce more IL-4 than IFN-gamma. In contrast, LTC from patients with non-AIH are dominated by CD8+ and CD4+ T cells that produce significantly less IL-4 than IFN-gamma. Thus, liver-infiltrating T cells from patients with AIH and non-AIH belong to different functional T cell subsets. This may have implications for the regulation of humoral and cellular immune responses in inflammatory liver disease.
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PMID:Analysis of the in vitro cytokine production by liver-infiltrating T cells of patients with autoimmune hepatitis. 840 1

Immunopathologic mechanisms leading to liver tissue injury in hepatitis caused by hepatitis A virus (HAV) were studied in an autologous in vitro model. Data show virus-specific killing by liver-infiltrating T lymphocytes in man and support the hypothesis that hepatocellular damage as well as efficient elimination of virus-infected hepatocytes is mediated by HLA-restricted, HAV-specific CD8+ T lymphocytes. Furthermore, experimental results demonstrate that human interferon-gamma produced by HAV-specific T cells may act as a key factor in T-cell-promoted clearance of HAV-infected hepatocytes. Besides the well-known hepatotropism, the myelotropic properties of HAV have some important clinical implications. Perturbations of hematopoietic regulation, ranging from transient granulocytopenia to rare cases of bone marrow failure, are associated with HAV infection. In an attempt to elucidate the pathogenetic mechanisms, we could show a direct suppressive effect of HAV on human bone marrow progenitors and a significant progressive decline in these cells in HAV-infected long-term bone marrow cultures.
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PMID:Hepatitis A: hepatotropism and influence on myelopoiesis. 840 40

An etiopathological link between hepatitis virus infection and autoimmune liver disease, in particular autoimmune hepatitis has been suggested. In some patients features of both viral and autoimmune disease are present. We have studied 352 patients with autoimmune liver disease and 507 patients with viral hepatitis for diagnostic characteristics as well as for evidence of an etiological connection. 38 of the 201 patients with hepatitis C (19%) and 42 of the 306 patients with hepatitis B (14%) had significant titres of autoantibodies (ANA, SMA or LKM). SLA autoantibodies were found exclusively in patients with autoimmune liver disease. LKM auto-antibody was found in only one of the 201 HCV patients. Evidence of past or present hepatitis B virus and past hepatitis A virus infection was most common in the hepatitis C virus patients and least common in autoimmune hepatitis. 28 of the 352 patients with autoimmune liver diseases tested positive in the second generation anti-HCV ELISA, but only five patients (two with autoimmune hepatitis, one with primary sclerosing cholangitis and two with primary biliary cirrhosis) were positive in confirmatory anti-HCV assays, and only in these could HCV-RNA be isolated. Autoimmune hepatitis patients had significantly higher transaminase, GLDH and IgG levels. HLA-B8, HLA-DR3 and HLA-DR4 were significantly more common in autoimmune hepatitis. Distinction between autoimmune liver disease and viral hepatitis C could be made reliably on clinical and laboratory grounds. Our data show that a link between hepatitis A, B, or C virus infection and autoimmune liver diseases is highly unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation between autoimmune liver diseases and viral hepatitis: clinical and serological characteristics in 859 patients. 852 56

As part of ongoing studies to define the nature of anti-nuclear antibodies in autoimmune hepatitis and assess their clinical significance, we tested sera from 65 patients who had previously been screened for reactivities to recombinant ribonucleoproteins (U1RNP-A and U1RNP-70K), ribonucleoprotein complexes (52K SSA/Ro and 60K SSA/Ro) and centromere (Cenp-B) for antibodies to histones by enzyme immunoassay. Twenty-three specimens were reactive to histones (35%). Eleven of the 23 seropositive specimens were also reactive to other nuclear antigens (48%); 12 specimens (52%) were reactive only to histone. Histone-reactive sera did not have a characteristic pattern by indirect immunofluorescence. Patients with antibodies to histones were indistinguishable from other by age, gender, clinical and laboratory findings. HLA phenotype, or responses to corticosteroid therapy. Eighteen sera (28%) that had demonstrated nuclear reactivity by indirect immunofluorescence lacked reactivity to the five recombinant nuclear antigens and histones. We conclude that antibodies to histones are common in autoimmune hepatitis and that they are an important species associated with antinuclear reactivity. In some patients, they may be the only findings. Seropositive patients lack distinctive features or different outcomes after therapy. Reactivities against other nuclear antigens probably exist and remain undefined.
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PMID:Frequency and significance of antibodies to histones in autoimmune hepatitis. 853 Aug 7

Chronic inflammatory liver diseases can be induced by virus infections, toxic-metabolic factors and/or autoimmune mechanisms. This overview deals with the immunopathogenesis of chronic hepatitis B and C and autoimmune hepatitis (AIH). 1. Chronic hepatitis B: The immune response to HBV-antigens is responsible both for viral clearance and disease pathogenesis during HBV-infection. The humoral immune response to HBsAg contributes to the clearance of circulating virus particles, the cell mediated immune response to HBsAg, HBcAg and polymerase antigen eliminates infected cells. The class I- and class II restricted T-cell-responses to HBV is strong, polyclonal and multispecific in acute HB with successful clearance of the virus, but weak or incomplete in chronic HB with viral persistence. In addition to ineffective immune response host and viral factors as well as abnormalities in virus-host interactions may be the main reasons for the maintenance of HBV-carrier status. 2. Chronic hepatitis C develop in more than 60% of infected patients. There is increasing evidence that the immune response to HCV-epitopes plays an important role in the course and the pathogenesis of the disease. It has been shown that CD4+ and CD8+ T-cells recognize viral peptides in the presence of class I and II molecules. The fine specificity and functional significance of liver infiltrating and peripheral blood T-cells demonstrate HCV specific immunodominant epitopes targeted by class Ii restricted CD4+ cells in patients with chronic HCV infection. The T-cell response correlates with disease activity. The cytokine release of T-cells resemble a TH1-like profile. Studies of the humoral immune response to HCV show a correlation between IgM-anti-HCV and disease activity. In vitro and in vivo anti-HCV secretion by PBMC is due to persistent antigenic stimulation of B-cells by ongoing production of viral antigens and reflects HCV replication in PBMC. Of special interest are several immune mediated disease and immune abnormalities in chronic hepatitis C. 3. Autoimmune hepatitis (AIH) is a distinct group of acute and chronic necro-inflammatory disorders of unknown etiology characterized by immunological and autoimmunological features including the presence of autoantibodies but without an antecedent of viral infections. Marker autoantibodies define 3 subtypes: Type I (ANA/SMA), Type II (LKM1-AB), Type II (SLA-AB). AIH is associated with a distinct genetic background (HLA A1, B8, DR3 or DR4). Several studies clearly demonstrate that liver cell damage in AIH is mediated by autoimmune reactions against normal constituents of hepatocytes. Although the precise mechanisms are not yet fully understood, there is now considerable evidence that autoantigens of the hepatocellular membrane in particular the ASGPR are important targets of liver damaging autoreactions in AIH. Cellular and humoral immune reactions against the human ASGPR correlate with disease activity and usually disappear under immunosuppressive therapy.
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PMID:[Immunopathology of chronic liver diseases]. 860 Jun 84

We present 10 Italian patients with type 2b autoimmune hepatitis (anti-LKMI positivity) and HCV infection. 6 patients had IgG concentrations above the upper limit of normal and all had histological features of chronic autoimmune hepatitis or chronic persistent hepatitis or cirrhosis. ANA and SMA were positive in 2 patients, pANCA in 3 patients. Anti-GOR were negative in all patients, 6 of them were HLA B8 DR3 and 2 HLA B8 DR4. Antibodies to HCV (tested by ELISA 2nd and 3rd generation) were positive in all patients and in 9 subjects were detected HCV RNA. The two patients with positivity for ANA and SMA were treated successfully with corticosteroids, but they relapsed after the drug withdrawal; the others received interferon, that had to be suspended in 2 patients because inducing an autoimmune thyroiditis. Although, at present, it is still not known if HCV is a really trigger factor in developing autoimmunity or if the two diseases are coincidental, the authors suggest that it is important for clinicians to use appropriate treatment strategies on the basis of the predominant illness.
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PMID:Type 2 autoimmune hepatitis and hepatitis C viraemia. 876 75

The aim of this study was to clarify the relationship between human leukocyte antigen DR allele distribution and the degree of liver cell injury of hepatitis C virus (HCV) carriers in Japan. The subjects, 68 HCV carriers, were divided into two groups according to the laboratory data and liver histology. Those in the asymptomatic carrier group (n = 19) had normal ALT levels persistently for 8-153 months (mean 25.7 months) and were diagnosed histologically as normal liver, nonspecific reactive hepatitis or chronic persistent hepatitis. Those in the chronic active hepatitis group (n = 49) had elevated ALT levels and were diagnosed histologically with chronic active hepatitis. The human leukocyte antigen DR alleles of all subjects were defined using the polymerase chain reaction restriction fragment length polymorphism method. The expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane were also examined in 14 patients from each group using an indirect immunohistochemical method. The frequency of DR13 (42.1%) in the asymptomatic carrier group was significantly higher (Pc < 0.003) than that of the chronic active hepatitis group (4.1%). There were no significant differences for the other DR alleles. The frequencies of expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane of the asymptomatic carrier group were significantly less than those of the chronic hepatitis group (64% vs. 100% P < 0.05, 29% vs. 71% P < 0.05, respectively), although there was no significant difference in the serum HCV-RNA titer between the two groups (10(6.4 +/- 1.1) vs. 10(6.5 +/- 0.7) copies/mL). These results demonstrate that the cellular immune response of the asymptomatic carrier group is less activated than the response of the chronic active hepatitis group and that HLA DR13 may be closely associated with this low activity of hepatitis among HCV carriers.
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PMID:Increased frequency of HLA DR13 in hepatitis C virus carriers with persistently normal ALT levels. 882 3


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