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)

In some patients differentiation between autoimmune hepatitis and chronic viral disease may be difficult. In patients with chronic active hepatitis the coincidence of various types of autoantibodies and antibodies to hepatitis C virus (HCV-Ab) has been reported. It is important to diagnose the true etiology of the underlying liver disease because treatment for viral disease and autoimmune hepatitis is different. This paper reports about five patients who were referred to the liver outpatient clinic with the diagnosis of chronic active hepatitis. All of them had antibodies to liver-pancreas-antigen (LP-Ab) and HCV-Ab. Some authors believe that LP-Ab and anti-soluble-liver-antigen antibodies (SLA-Ab) are found with the same entity of autoimmune hepatitis. Nevertheless none of our patients had detectable antibodies against Cytokeratin 8/18, the major target antigen of SLA-Ab positive autoimmune hepatitis. Serum transaminases were elevated for more than 6 months and all patients were positive for HCV-RNA by PCR. Three patients had a history of exposure to blood products. In all five patients liver biopsy showed chronic active hepatitis compatible with chronic hepatitis C. All patients were treated with alfa-interferon. In four of five patients interferon led to improvement or normalization of serum transaminases. Thus we conclude that in a considerable number of patients with chronic active hepatitis associated with both LP-Ab and HCV-Ab, hepatitis C virus is the true etiology. Such patients with both LP-Ab and HCV-Ab may successfully be treated with alfa-interferon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differentiation between autoimmune hepatitis and hepatitis C virus related liver disease. 768 2

Complete congenital heart block is a serious complication of neonatal lupus erythematosus which most often occurs in children of mothers suffering from connective tissue disease. We report the occurrence of complete congenital heart block associated with autoimmune hepatitis (SLA-positive). A 32-year-old woman was treated for more than 10 years for autoimmune hepatitis (SLA-/ANA-positive) and remained in clinical remission under immunosuppressive therapy. She showed an MHC-haplotype typical for autoimmune hepatitis (A1, B8, DR3). After a normal first pregnancy, an emergency caesarean section was performed in the 32nd week of her second pregnancy because of fetal bradycardia. The child died a few hours after delivery of complete congenital AV-block. Retrospective analysis of the maternal serum showed the emergence of SS-A/Ro-antibodies prior to the second pregnancy. The maternal serum antibodies were reactive with the 52 kD SS-A/Ro-antigen, as demonstrated by immunoblot employing recombinant SSA/Ro-antigen. The occurrence of complete congenital heart block has been shown to be associated with the presence of SS-A/Ro antibodies as well as the MHC-haplotype DR3. With respect to this genetic linkage, pregnant patients with autoimmune hepatitis and the MHC-haplotype DR3 should be examined for the presence of SS-A/Ro-antibodies. They should be closely followed during pregnancy to enable early detection of the development of congenital heart block, as prevention by plasmapheresis plus dexamethasone may be possible at an early stage.
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PMID:Complete congenital heart block in autoimmune hepatitis (SLA-positive). 798 13

Acute and chronic autoimmune hepatitis are uncommon inflammatory liver diseases, mainly occurring in young women, in association with hypergammaglobulinemia and serum autoantibodies. Different types have been described: type 1 characterized by anti-smooth muscle and anti-nuclear antibodies; type 2 characterized by anti-LKM1 antibodies; type 3 characterized by anti-SLA antibodies. Other types, still not clearly defined, may exist. Autoimmune hepatitis are associated with HLA A1 B8 DR3 and HLA DR4. Without any treatment, the disease leads to cirrhosis and, uncommonly, to fulminant hepatitis. Large doses of corticosteroids usually allow to control the disease. Relapse of hepatitis is frequent after corticosteroid withdrawal. Concomitant administration of immunosuppressive agents such as azathioprine allows to reduce corticosteroid dosage and contributes to maintain the remission of the disease. Liver transplantation may be indicated in cases of severe cirrhosis or fulminant hepatitis.
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PMID:[Autoimmune hepatitis]. 817 63

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

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

Antineutrophil cytoplasmic antibodies (ANCA) are a group of autoantibodies first associated with Wegener's granulomatosis (WG). In autoimmune liver diseases, ANCA have been described recently in patients with primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). Controversy exists about the prevalence and specificity of ANCA in patients with autoimmune liver diseases. The purpose of this study was first to assess the prevalence of antineutrophil antibodies in patients with primary biliary cirrhosis and second to identify possible target antigens of antineutrophil antibodies. Sera from 33 patients with PBC, 75 patients with AIH, 16 patients with PSC, 90 control sera (chronic hepatitis B, chronic hepatitis C, alcoholic liver cirrhosis, systemic lupus erythematosus) and sera from healthy blood donors were enrolled in the present study. ANA and ANCA were detected using standard protocols, antibodies against the nuclear antigen SP100 were detected by ELISA with recombinant antigen, antibodies against neutrophil alpha-granules were detected by ELISA. P-ANCA were found in two of 33 PBC sera, both patients presented with PBC/AIH overlap syndrome. In six of 33 (18%) PBC sera a nuclear dot like immunofluorescence pattern (antineutrophil nuclear antibodies, ANNA) was observed. These dots were small in size and located all over the nucleus, the anti-SP100 fluorescence. This result was confirmed by IFT on HEp-2 cells and by ELISA. High tier antibodies against SP100 were found to be specific for patients with PBC. Comparing the IFT results on HEp-2 cells and human neutrophils, we found an excellent correlation (Spearman's rank correlation coefficient = 0.968, P < 0.001). ANCA were detected in AIH type-1 (75%), SLA-positive AIH (36%) and PSC (63%). AIH type-2 was found to be ANCA negative. All PSC contained no antibodies against neutrophil alpha-granules. Our results show: 1. P-ANCA in patients with PBC indicate a PBC/AIH overlap syndrome; 2. ANNA in patients with PBC are mostly directed against SP100; 3. neutrophil granule components are not the ANCA specific antigens in patients with PSC.
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PMID:Antineutrophil nuclear antibodies (ANNA) in primary biliary cirrhosis: their prevalence and antigen specificity. 906 1

Autoimmune hepatitis (AIH) is a rare disease, characterized by female predominance, hypergammaglobulinemia, autoantibodies, association with HLA DR3 and HLA DR4 and a good response to immunosuppression. Different subtypes of AIH may be distinguished, based on differences in the autoantibody patterns. AIH type 1 is characterized by anti-nuclear (ANA) and/or anti-smooth muscular (SMA) autoantibodies. AIH type 2 is characterized by liver/kidney microsomal autoantibodies (LKM). AIH type 3 may be distinguished by autoantibodies to soluble liver proteins (SLA) or the liver pancreas antigen (LP). AIH-2 affects predominantly pediatric patients and is characterized by a more severe clinical course, a higher frequency of relapse under immunosuppressive treatment and a more frequent progression to cirrhosis. In contrast, AIH types 1 and 3 show a higher age of onset and a better long-term response to immunosuppressive treatment. At present, the treatment of choice is prednisone alone or a combination with prednisone and azathioprine. Both treatment protocols show high survival rates. However, a rate of 13% of treatment failures and the failure to induce permanent remission in most patients underlines the urgent need to develop additional treatment regimens. A yet unknown genetic predisposition is believed to act as the underlying etiological factor in AIH. This genetic predisposition includes a few known risk factors such as the presence of HLA DR3 or HLA DR4, deletions of C4A alleles and female gender. Furthermore, it has to be postulated that defects in immunoregulatory genes exist. A model for such defects may be the autoimmune polyglandular syndrome type 1 (APS1), which results from the defects in a single gene, the autoimmune regulator type 1 (AIRE-1). Patients with APS1 suffer from mucocutaneous candidiasis and a number of organ-specific autoimmune diseases. Characteristic is a high variability in the number and character of the disease components in APS1, indicating that other genetic and environmental factors may strongly modulate the outcome of disease. Environmental factors may comprise chemical influences, such as nutritional compounds and drugs, or virus infections. Several drugs or chemicals were shown to induce hepatitis with autoimmune involvement, e.g. tienilic acid, dihydralazine and halothane. Adduct formation of an activated metabolite is believed to act as a trigger and to induce a specific immune response. Similarly, viruses were repeatedly shown to trigger autoimmune hepatitis. In virus infections, sequence similarities between viral and self-proteins may trigger autoimmune processes and the simultaneous presence of inflammatory cytokines during virus infection may further increase the risk of developing self-perpetuating autoimmune reactions which overshoot.
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PMID:Autoimmune hepatitis. 1072 4

Prevalence and clinical relevance of antibodies to soluble liver antigen (tRNP((Ser)Sec)/SLA) in autoimmune hepatitis (AIH) have been investigated using partially purified or prokaryotically expressed antigen. The aim of this study was to improve the detection of anti-tRNP((Ser)Sec)/SLA by establishing an immunoassay that was able to identify antibodies directed to conformational epitopes and to investigate the clinical implication of this autoantibody in autoimmune liver disease. By using eukaryotically expressed tRNP((Ser)Sec)/SLA as target in a radioligand assay (RLA), 81 patients with autoimmune liver disease (AILD) (33 type 1 AIH, 31 type 2 AIH, and 17 autoimmune sclerosing cholantitis [ASC]), 147 pathologic, and 56 healthy controls were investigated. RLA results were compared with those obtained using a commercial enzyme-linked immunosorbent assay (ELISA) and immunoblot. Reactivity to tRNP((Ser)Sec)/SLA was present in 58% of patients with type 1 and type 2 AIH, 41% with ASC, but in only 3 pathologic controls. RLA was similarly disease-specific but remarkably more sensitive than ELISA and immunoblot. A prospective study showed that anti-tRNP((Ser)Sec)/SLA-positive patients run a severe clinical course, having worse histology, needing longer to achieve remission, relapsing and requiring liver transplantation or dying more frequently than anti-tRNP((Ser)Sec)/SLA negative patients. Anti-tRNP((Ser)Sec)/SLA production was favored by the possession of DR3 and A1-B8-DR3 in AIH type 1 and ASC, and prevented by the possession of A2 in all 3 types of AILD, particularly in type 2 AIH. In conclusion, anticonformational tRNP((Ser)Sec)/SLA reactivity is frequent in type 1 and type 2 AIH and ASC, defining patients with a worse prognosis.
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PMID:Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease. 1219 75

We have recently reported that anti-SLA seropositive autoimmune hepatitis (AIH) patients develop autoantibodies against glutathione S-transferase (GST). GSTs are multifunctional enzymes mediating hepatic detoxification of cytotoxic and genotoxic compounds and are also involved in biliary secretion. We have observed varying reactivity of individual AIH sera towards several GST isoenzymes. Since the GST subunits have very similar molar masses and therefore are not satisfactorily resolved by one-dimensional gel electrophoresis, we have performed their fractionation by reverse-phase high performance liquid chromatography (HPLC) to better separate the individual GST isoenzymes. 4 individual GST subunits were isolated as judged by electrophoretic analysis of the 4 distinct peaks. The identity of isolated proteins was unequivocally determined by protein sequencing. Isolated subtypes were loaded on 15% SDS gels and blotted. Immunoblotting was performed with eleven anti-SLA positive sera that displayed differential reactivity with total GSTs. Fractionation of the GSTs by HPLC did not impair their ability to react with specific autoantibodies. Interestingly, the majority of GST-positive AIH sera reacted with one or two GST subtypes, only two sera recognized 3 subunits. Ya was most prevalent autoantigen. Autoantibodies against Yb2 were detected solely in one serum. This pattern of reactivity indicates that individual patients' sera discriminate between GST subunits despite their sequence homology. It is well known that the GST variants differ within their amino-terminal part while the residual moiety is highly conserved. It would suggest that autoantibodies recognize distinct epitopes located within amino-terminus of individual GST variants.
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PMID:Anti-SLA seropositive autoimmune hepatitis sera recognize distinct subunits of glutathione S-transferase: high prevalence of the Ya autoantigen. 1203 Apr 35

We describe the case of a patient with chronic hepatitis C (CHC) who showed a progressive increase in aminotransferase level, reaching values of aspartate aminotransferase 1723 UI/L, alanine aminotransferase 1519 UI/L and gamma-glutamyl-transpeptidase 296 with a bilirubin level of 6 mg/dL and direct bilirubin level of 4.6 mg/dL. One year previously, the patient had been diagnosed with CHC, genotype 1, and had an initial hepatitis C virus RNA load of 249,000 UI/mL. All the specific blood tests performed were negative except for antisoluble liver antigen (anti-SLA) antibodies, which were positive in two different determinations. A diagnosis of overlap syndrome CHC and autoimmune hepatitis was made. Steroid and azathioprine treatment was started with good response. The relationship between CHC and anti-SLA is not well characterized but has been described in these patients. We found no prior reports in the literature of CHC associated with positive anti-SLA in a patient with persistent acute hepatitis.
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PMID:[Persistent acute hepatitis in a patient with chronic hepatitis C]. 1702 Jun 78


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