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)

Interferons (IFNs) have immunomodulatory properties such as direct increase in the production of pathogen autoantibodies, enhanced cytotoxic T cell and B cell activities, inhibition of T suppressor cell function and induction of HLA class I antigen expression. These actions of IFN induce autoimmune disorders including autoimmune thyroiditis, hemolytic anemia and thrombocytopenia, SLE, rheumatoid arthritis and psoriasis, however, these autoimmune diseases except for autoimmune thyroiditis, are rare among side effects of IFN therapy. Most of the patients showing these autoimmune disorders during IFN treatment have predisposal immunological abnormalities such as positive ANA and antithyroidal autoantibodies. We described here autoimmune disorders during and after IFN treatment among 1023 cases with chronic active type C hepatitis. The cases with SLE, thrombocytopenic purpura, rheumatoid arthritis and psoriasis showed good prognosis after cessation of IFN administration.
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PMID:[Autoimmune disorders in interferon therapy]. 752 40

In summary, type 1 autoimmune hepatitis is infrequently associated with serologic markers of viral infection, and there is no direct evidence that viruses are important causes of this disease. Patients seropositive for anti-LKM1 are commonly infected with HCV, but these patients have predominant features of chronic viral hepatitis and frequently lack antibodies to P450IID6. Such patients respond to therapy with interferon and should be distinguished from patients with type 2 autoimmune hepatitis who have anti-P450IID6, seronegativity for anti-HCV, and responsiveness to corticosteroids. In patients with ANA and/or SMA seropositivity and anti-HCV, a false-positive reaction for anti-HCV must be excluded by recombinant immunoblot assay. Patients with false anti-HCV seropositivity should be treated with corticosteroids. In contrast, patients with a true viral infection and low-titer autoantibodies should be treated with interferon. In patients with true viral infection and high titers of auto-antibodies, the treatment decision must balance the autoimmune and viral manifestations. An empiric trial of corticosteroids is justified if autoimmune features predominate.
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PMID:Autoimmune hepatitis and viral infection. 752 73

Viral infections are considered a possible trigger of autoimmune diseases. In autoimmune liver diseases the hepatotropic viruses, especially hepatitis C virus (HCV), have received particular attention as possible etiological agents. The present study was undertaken to investigate the relation between hepatitis virus infections and autoimmune liver diseases. We found a very low incidence of HCV infection in patients with autoimmune liver diseases. Only 5% (n = 7) of patients with AIH types I and III had antibodies against HCV antigens, but only two of these seven were HCV-RNA positive. Similar results were obtained in patients with PBC and PSC. Furthermore, the coexistence of LKM autoantibodies with chronic HC is a rare event and less common than low-titer ANA and SMA in viral liver diseases. In conclusion, a link between hepatitis viruses B or C and AI-liver diseases is very unlikely. Autoantibodies in viral liver diseases appear to be an expression of a generalized immune activation by cytokines, as observed during interferon treatment in viral liver diseases.
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PMID:The role of autoimmunity in hepatitis C infection. 760 86

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

Diclofenac is a frequently prescribed nonsteroidal antiinflammatory drug (NSAID). Significant hepatotoxicity related to diclofenac may be more common than previously recognized, as three patients with diclofenac-associated hepatitis were seen by one clinician in a single year. All patients were ANA positive during the hepatitis and had histologic features of chronic active hepatitis. Two had been inappropriately treated with corticosteroids. The third patient presented more acutely with jaundice and symptoms of hepatitis. Two of the patients developed the same hepatic reaction when rechallenged with diclofenac. The third patient was changed to tiaprofenic acid, a NSAID of the same family, and redeveloped evidence of hepatotoxicity. All three were subsequently able to take naproxen without liver dysfunction. Diclofenac-induced liver disease may be misdiagnosed. Twenty-six cases of significant hepatic reactions to diclofenac have been previously reported in the literature and are reviewed. Such hepatic reactions to diclofenac and related NSAIDs may be commoner than realized. Introduction of a NSAID of another class appears to be safe.
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PMID:Diclofenac induced hepatitis. 3 cases with features of autoimmune chronic active hepatitis. 846 74

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

We herein report a case of chronic hepatitis C where the patient developed severe thrombocytopenia during interferon therapy. The patient was a 61-year-old woman, who received interferon therapy on April 27, 1993 under the diagnosis of C type chronic active hepatitis. After 4 weeks, her platelet count had decreased to 18,000/microliters and intraoral hemorrhage had begun. Although she received 250 mg of methylprednisolone and 20 U of platelet transfusion three times, her platelet count continued to decrease to 4,000/microliters on both May 28, and on June 3, 1993, and so she was transferred to our hospital on June 4. On her second admission to our hospital, although the platelet-associated IgG (PA-IgG) had increased markedly and the megakaryocytes in her bone marrow had decreased, her platelet count had already increased to 37,000/ microliters, and this gradually returned to a normal level accompanied with a decrease of PA-IgG within one month In this case, although we found immunological abnormalities (high level of IgG, positive ANA and positive anti-smooth muscle antibody) prior to interferon treatment, we could not diagnose the patient as having suffered from autoimmune disease, including autoimmune hepatitis, because she did not satisfy the necessary criteria and because she did not have any symptoms suggesting autoimmune disease. We consider that there may be the possibility that interferon induced only an anti-platelet antibodies that caused the high level of PA-IgG and decreased the production level of platelets within the bone marrow.
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PMID:[Anti-platelet antibody and severe thrombocytopenia during interferon-alpha therapy for chronic active hepatitis C]. 870 92

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 number of autoantibodies associated with chronic liver disease continues to burgeon and characterization of these immunoreactivities will undoubtedly enhance understanding of the autoantigens that are targeted by cytodestructive immunocytes. Assays for the majority of these immunoserological species are not generally available and in most instances, assessments are restricted to individual laboratories with vested interests in characterizing a particular species. For clinical diagnosis and management of autoimmune liver disease, assays for ANA, SMA, anti-LKM1 and AMA are essential. This conventional armamentarium, however, must be upgraded on a regular basis to ensure availability and application of the most useful assays. Unfortunately, there are no formal mechanisms for improving the diagnostic resources and standardizing testing strategies. An important first step must be taken by the basic laboratories that advocate individual assay systems. These facilities must share methodologies and exchange serum samples so that the most clinically pertinent and cost-effective immunoserological batteries can be defined and promulgated. Industry can then respond to need and facilitate the commercialization of assays for general use. Currently, the assays that warrant dissemination are those that detect antibodies to the E2 subunits of the pyruvate dehydrogenase complex and antibodies to asialoglycoprotein receptor. Both assays have high diagnostic specificity and each reflects reactivity to an important target autoantigen of probable pathogenic importance. Each autoantibody species can supplant conventional assays such as those for AMA and ANA and they each may impart useful clinical information. In the case of antibodies to the E2 subunits, titres may reflect histological progression of PBC. In the case of anti-ASGPR, disappearance of the autoantibodies in patients with autoimmune hepatitis may secure a confident treatment end-point. Great progress has been made in defining the immunoserological manifestations of chronic liver disease but little has been done to distribute the resources.
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PMID:Autoantibodies. 890 2


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