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)

Autoimmune hepatitis is rarely described in combination with antiphospholipid syndrome. So far, only cases have been presented where the secondary antiphospholipid syndrome occurred as an effect of autoimmune hepatitis. We report on a 56-year-old Caucasian female with a history of thrombosis, thrombocytopenia and the detection of anti-cardiolipin antibodies. Interestingly, a few years later the patient developed liver failure with highly elevated liver enzymes. The immunological antibody pattern verified the diagnosis of type I autoimmune hepatitis, and immunosuppressive therapy led to the recovery of the patient. Thus, we present the first case of autoimmune hepatitis as a consequence of primary antiphospholipid syndrome.
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PMID:Antiphospholipid syndrome in combination with autoimmune hepatitis. 1567 4

Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver characterized by hypergammaglobulinemia, characteristic autoantibodies, association with HLA DR3 or DR4 and a favorable response to immunosuppressive treatment. The etiology is unknown. The detection of non-organ and liver-related autoantibodies remains the hallmark for the diagnosis of the disease in the absence of viral, metabolic, genetic, and toxic etiology of chronic hepatitis or hepatic injury. The current classification of AIH and the several autoantibodies/target-autoantigens found in this disease are reported. Current aspects on the significance of these markers in the differential diagnosis and the study of pathogenesis of AIH are also stated. AIH is subdivided into two major types; AIH type 1 (AIH-1) and type 2 (AIH-2). AIH-1 is characterized by the detection of smooth muscle autoantibodies (SMA) and/or antinuclear antibodies (ANA). Determination of antineutrophil cytoplasmic autoantibodies (ANCA), antibodies against the asialoglycoprotein receptor (anti-ASGP-R) and antibodies against to soluble liver antigens or liver-pancreas (anti-SLA/LP) may be useful for the identification of patients who are seronegative for ANA/SMA. AIH-2 is characterized by the presence of specific autoantibodies against liver and kidney microsomal antigens (anti-LKM type 1 or infrequently anti-LKM type 3) and/or autoantibodies against liver cytosol 1 antigen (anti-LC1). Anti-LKM-1 and anti-LKM-3 autoantibodies are also detected in some patients with chronic hepatitis C (HCV) and chronic hepatitis D (HDV). Cytochrome P450 2D6 (CYP2D6) has been documented as the major target-autoantigen of anti-LKM-1 autoantibodies in both AIH-2 and HCV infection. Recent convincing data demonstrated the expression of CYP2D6 on the surface of hepatocytes suggesting a pathogenetic role of anti-LKM-1 autoantibodies for the liver damage. Family 1 of UDP-glycuronosyltransferases has been identified as the target-autoantigen of anti-LKM-3. For these reasons the distinction between AIH and chronic viral hepatitis (especially of HCV) is of particular importance. Recently, the molecular target of anti-SLA/LP and anti-LC1 autoantibodies were identified as a 50 kDa UGA-suppressor tRNA-associated protein and a liver specific enzyme, the formiminotransferase cyclodeaminase, respectively. Anti-ASGP-R and anti-LC1 autoantibodies appear to correlate closely with disease severity and response to treatment suggesting a pathogenetic role of these autoantibodies for the hepatocellular injury. In general however, autoantibodies should not be used to monitor treatment, predict AIH activity or outcome. Finally, the current aspects on a specific form of AIH that may develop in some patients with a rare genetic syndrome, the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) are also given. Autoantibodies against liver microsomes (anti-LM) are the specific autoantibodies detected in AIH as a disease component of APECED but also in cases of dihydralazine-induced hepatitis. Cytochrome P450 1A2 has been identified as the target-autoantigen of anti-LM autoantibodies in both APECED-related AIH and dihydralazine-induced hepatitis. The latter may indicate that similar autoimmune pathogenetic mechanisms can lead to liver injury in susceptible individuals irrespective of the primary defect. Characterization of the autoantigen-autoantibody repertoire continues to be an attractive and important tool to get access to the correct diagnosis and to gain insight into the as yet unresolved mystery of how hepatic tolerance is given up and AIH ensues.
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PMID:Autoantibodies and autoantigens in autoimmune hepatitis: important tools in clinical practice and to study pathogenesis of the disease. 1567 7

Autoimmune hepatitis is a self-perpetuating hepatocellular inflammation. The diagnosis is established by a number of diagnostic criteria, defined by the International Autoimmune Hepatitis Group, and the exclusion of other causes of chronic hepatitis. There are two fundamental goals in therapy: induction of remission and maintenance of remission. The standard initial treatment is prednisone monotherapy or combination therapy with prednisone and azathioprine, which induce a clinical, biochemical and histologic remission in 65-87% of patients within 3 years. Other typical treatment endpoints in autoimmune hepatitis are an incomplete response, treatment failure and intolerance of the administrated drugs. If the treatment results are unsatisfactory, liver transplantation and alternative drugs such as Cyclosporin A, tacrolimus, cyclophosphamide, mycophenolate mofetil, budesonide, ursodeoxycholic acid should be considered; however, efficacy in clinical trials has not been shown. Future investigations must focus on the clarification of pathogenic mechanisms, characterization of target autoantigens, identification of host susceptibility factors, and assessment of alternative treatment strategies.
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PMID:[Autoimmune hepatitis: new diagnostic and therapeutic approach]. 1568 53

New drugs and advances in molecular biology afford opportunities to upgrade the treatment of autoimmune hepatitis. The aims of this study were to define treatment problems, identify possible solutions, and stimulate investigations to improve patient care. A clinical subcommittee of the International Autoimmune Hepatitis Group reviewed current management difficulties and proposed corrective actions. The assessment of new front-line and salvage therapies for adults and children were given top priority. Cyclosporine and mycophenolate mofetil were endorsed as drugs worthy of rigorous study in severe disease, and budesonide was endorsed for study as front-line therapy in mild disease. Diagnostic criteria and treatment regimens for children required codification, and pharmacokinetic studies were encouraged to develop optimal dosing schedules based on therapeutic ranges. Collaborative efforts were proposed to help understand racial, geographical, and genetic factors affecting outcome and to establish definitions and therapies for variant syndromes and graft dysfunction after transplantation. The development of experimental animal models was deemed essential for the study of site-specific molecular interventions, and gene therapy was endorsed as a means of bolstering reparative processes. In conclusion, evolving pharmacological and technical advances promise to improve the treatment of autoimmune hepatitis, and investigations of these advances are timely, feasible, and necessary.
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PMID:Treatment challenges and investigational opportunities in autoimmune hepatitis. 1569 Apr 85

Autoimmune hepatitis can affect diverse ethnic groups, and its clinical expression and outcome can vary accordingly. An asymptomatic presentation may identify patients who respond more readily to medication. Celiac sprue is important to recognize and treat by gluten restriction. Centrilobular necrosis and coincidental destructive cholangitis do not preclude the diagnosis, and antibodies to soluble liver antigen/liver pancreas may identify patients susceptible to relapse. Women, who have non-DRB1*0401 DR4 alleles more commonly than do men, may respond to a diverse range of autoantigens. DRB1*1301 is associated with autoimmune hepatitis in Brazil, especially among children, and it may favor an indigenous triggering agent. Variant syndromes are heterogenous conditions that probably reflect referral biases, and molecular mimicry between foreign and self-antigens is the basis for most theories of pathogenesis. Immunosuppressive medications (eg, cyclosporine, mycophenolate mofetil) have been used empirically with success, and recurrent and de novo disease after liver transplantation must be considered in all patients with graft dysfunction.
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PMID:Autoimmune liver disease. 1570 63

Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.
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PMID:Autoimmune hepatitis. 1572 81

Autoimmune hepatitis (AIH) is a disease of unknown etiology, characterized by liver-related autoantibodies. Autoimmune hepatitis is subdivided into two major types: AIH type 1 is characterized by the detection of ANA, SMA, ANCA, anti-ASGP-R, and anti-SLA/LP. Autoimmune hepatitis type 2 is characterized to be mainly related with drug-metabolizing enzymes as autoantigens, such as anti-LKM (liver-kidney microsomal antigen)-1 against CYP2D6, anti-LKM-2 against CYP2C9-tienilic acid, anti-LKM-3 against UGT1A, and anti-LC1 (liver cytosol antigen)-1 and anti-APS (autoimmune polyglandular syndrome type-1) against CYP1A2, CYP2A6, and others. Anti-LKM-1 sera inhibited CYP2D6 activity in vitro but did not inhibit cellular drug metabolism in vivo. CYP2D6 is the major target autoantigen of LKM-1 and expressed on plasma membrane (PM) of hepatocytes, suggesting a pathogenic role for anti-LKM-1 in liver injury as a trigger. Anti-CYP1A2 was observed in dihydralazine-induced hepatitis, and radiolabeled CYP1A2 disappeared from the PM with a half-life of less than 30 min, whereas microsomal CYP1A2 was stably radiolabeled for several hours. Main antigenic epitopes on CYP2D6 are aa 193-212, aa 257-269, and aa 321-351; and D263 is essential. The third epitope is located on the surface of the protein CYP2D6 and displays a hydrophobic patch that is situated between an aromatic residue (W316) and histidine (H326). Some drugs such as anticonvulsants (phenobarbital, phenytoin, and carbamazepine) and halothane are suggested to induce hepatitis with anti-CYP3A and anti-CYP2E1, respectively. Autoantibodies against CYP11A1, CYP17, and/or CYP21 involved in the synthesis of steroid hormones are also detected in patients with adrenal failure, gonadal failure, and/or Addison disease.
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PMID:Autoantibodies against CYP2D6 and other drug-metabolizing enzymes in autoimmune hepatitis type 2. 1574 2

Autoimmune hepatitis is a rare disease with unclear pathogenesis. Several viruses have been proposed to act as triggering agents for the inflammatory process of the disease; however, HIV has only very rarely been reported to be associated. We report a case of a patient with autoimmune hepatitis and HIV infection. The possible pathogenetic mechanism is discussed. Antiretroviral treatment led to normalization of liver biochemistry, supporting the hypothesis of HIV induced autoimmune hepatitis.
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PMID:Autoimmune hepatitis in an HIV infected patient that responded to antiretroviral therapy. 1576 6

Autoimmune hepatitis has a global occurrence, diverse clinical phenotype, and evolving treatment options. The goals of this report are to review the codified diagnostic criteria, spectrum of clinical presentations, proposed pathogenic mechanisms, conventional treatment strategies, and promising interventions. The literature published in English from 1980-2005 was reviewed and an updated current perspective provided. Autoimmune hepatitis affects all ages, may be asymptomatic, frequently has an acute onset, and can present as fulminant hepatitis. Perivenular (zone 3) necrosis is within the histological spectrum. Autoimmune hepatitis can recur or develop de novo after liver transplantation. CD4+ T-helper cells and natural killer T cells have been implicated in the pathogenesis, and molecular mimicry may break self-tolerance. DRB1*0301 and DRB1*0401 are the susceptibility alleles among white North Americans and northern Europeans, whereas diverse alleles of HLA DR4 have been associated with the disease in Japan, mainland China, and Mexico. DRB1*1301 is associated with autoimmune hepatitis in South American children, and it may predispose to an indigenous etiologic agent. Antibodies to soluble liver antigen/liver pancreas may have prognostic importance, and cyclosporine and mycophenolate mofetil must be assessed by clinical trial before incorporation into management algorithms. Site-specific interventions are feasible, and they require a confident experimental animal model for evaluation. Variant syndromes lack diagnostic and therapeutic guidelines. In conclusion, autoimmune hepatitis must be considered in all patients with acute and chronic liver disease and those with allograft dysfunction after transplantation. New immunosuppressive agents and site-specific interventions promise to improve care.
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PMID:Current concepts in autoimmune hepatitis. 1579 57

A 68-year-old woman with Felty's syndrome was admitted to our hospital due to breathlessness. She was diagnosed as having rheumatoid arthritis at age 59 years. Abdominal computed tomography indicated ascites, splenomegaly and liver atrophy. She had no antigens or antibodies for hepatitis virus, or antibodies for mitochondria with the exception of antinuclear antibody. According to the International Autoimmune Hepatitis (AIH) scoring system, she was diagnosed as having chronic hepatitis, compatible with AIH. The association of Felty's syndrome with AIH is very rare and the most difficult problem to overcome is whether or not steroid therapy is necessary in patients with Felty's syndrome complicated by AIH.
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PMID:Felty's syndrome with chronic hepatitis and compatible autoimmune hepatitis: a case presentation. 1589 48


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