A J Czaja

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..Ethnic-based deviations from classical phenotypes and the frequency of late-stage disease can complicate the diagnosis and management of autoimmune hepatitis in non-white populations...

..Development of these feasible new interventions for autoimmune hepatitis requires therapeutic animal models, societal support, and a collaborative network of investigators to conduct rigorous clinical trials...

..None has been licensed for use in autoimmune hepatitis, and their applications have been based on results from small singlecenter experiences...

..The nonstandard, nonsteroidal medications are mainly salvage therapies with off-label indications that must be used in highly individualized and well-monitored clinical situations...

..It is emerging as a frontline treatment, especially for noncirrhotic patients with uncomplicated disease...

..The substitution of mycophenolate mofetil for azathioprine and switch of the calcineurin inhibitor or its replacement with rapamycin have also been used for refractory disease. Re-transplantation has been necessary in 8-23 %...

..Standard treatment regimens for autoimmune hepatitis can be upgraded without adjustments that require major new expertise...

..The pathogenic mechanisms are presumed to be identical to those of classical disease. Autoantibody-negative autoimmune hepatitis is an infrequent but treatable disease that must be considered in unexplained acute and chronic hepatitis...

..Autoimmune hepatitis is a model of autoreactivity that reflects multiple disturbances in the counter-regulatory mechanisms essential for immune homeostasis...

..Progress has been made in the diagnosis and treatment of autoimmune hepatitis, but more work must be done. Multicenter clinical trials are essential before the incorporation of new drugs into the treatment algorithm...

..The existence of a mild form of autoimmune hepatitis that does not require treatment remains controversial. The aim of this study was to determine the existence, characteristics and outcome of this form...

..Each system has attributes that can be exploited...

..Prednisone and azathioprine are effective in the treatment of autoimmune hepatitis, but diverse side effects can diminish their net benefit...

..To review studies that improve the diagnosis and treatment of autoimmune hepatitis and extend understanding of its pathogenic mechanisms...

..Treatment failure is uncommon in the elderly, and age-related changes in the cellular immune response may attenuate the disease and enhance its response to therapy. Concurrent adjuvant therapies must focus on maintenance of bone density...

..Neoplastic changes typically are cytologic transformations rather than injury patterns, and they are not discussed here...

..01). Only patients with primary sclerosing cholangitis had a comparable occurrence of HLA DRB1*13. In conclusion, HLA DRB1*13 may be a genetic risk factor for some white North American patients with type 1 autoimmune hepatitis...

..Confident animal models of the human disease and a collaborative network of clinical investigators are the requisites for progress...

..The aim of this article is to review studies that improve the diagnosis and treatment of autoimmune hepatitis and suggest new drug and molecular interventions...

..These lessons may be applicable to autoimmune disease in general...

..To review studies that clarify the rheumatic manifestations of autoimmune hepatitis, elucidate shared pathogenic pathways, and encourage innovative site-specific therapies...

..We conclude that routine screening of blood thiopurine methyltransferase levels has a low yield for identifying individual patients at risk for azathioprine toxicity during conventional low dose therapy for autoimmune hepatitis...

..To determine the clinical phenotype and outcome of patients with definite type 1 autoimmune hepatitis, who lack human leukocyte antigen (HLA) DR3 and DR4, and to assess the importance of HLA DR7 and DR13...

..Variant syndromes should be suspected if cholestatic features are prominent and conventional treatment is ineffective...

..To review studies that improve the diagnosis and treatment of autoimmune hepatitis and extend the understanding of its pathogenic mechanisms...

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..The 1- and 5-year survivals after liver transplantation have ranged from 72-85% to 58-73%, respectively...

..Relapse after corticosteroid withdrawal probably does not occur, and its absence distinguishes drug-induced disease from classical autoimmune hepatitis...

..A retrospective study was performed to determine the bases for the classification of probable autoimmune hepatitis and its clinical importance...

..Autoimmune hepatitis is defined by a conventional battery of autoantibodies that may also be present in other liver diseases...

..Autoimmune hepatitis exemplifies an evolutionary process in the science of autoimmunity and the people committed to its study. Lessons derived from this experience can be far-reaching...

..Vaccination or infection of murine models with viral vectors carrying human antigens are the most recent developments. Animal models promise to extend the knowledge of etiological agents and improve treatment algorithms...

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..Progress has been made in identifying the serological markers of prognosis in autoimmune liver disease, and they promise to reflect critical disease mechanisms and enhance patient management...

..Identification of the key defects in immune homeostasis and antigen targets will direct new therapies...

..Relapse of autoimmune hepatitis after corticosteroid withdrawal is common, but the outer limit for this occurrence and the appropriate post-treatment surveillance strategy are uncertain...

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..Progress in the development of an animal model of autoimmune hepatitis and experiences in other immune-mediated diseases justify the evaluation of site-specific molecular and cellular interventions in this disease...

..The special clinical challenges are essential to recognize and treat properly, and they may also extend hypotheses of pathogenesis...

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..Corticosteroid therapy is effective in type 1 autoimmune hepatitis. This study determines if the rapidity of response affects outcome...

..To review studies that improve the diagnosis and treatment of autoimmune hepatitis and presage new drug and molecular site-specific interventions...

..Short-term therapy, however, does not facilitate reduction in the dose of corticosteroids or its withdrawal, affect clinical outcome, or reduce histological activity...

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..Relapse of type 1 autoimmune hepatitis after drug withdrawal may relate to incomplete histological improvement during corticosteroid therapy and/or persistence of pathogenic mechanisms...

..Antibodies to soluble liver antigen/liver pancreas are highly specific markers of autoimmune hepatitis...

..These advances may in turn clarify pathogenic mechanisms, facilitate the development of animal models, and generate novel site-specific therapies...

..Critical mechanisms of immunocyte activation, cytotoxic T cell expansion, and cytokine modulation are the targets of site-specific interventions...

..Our goal was to determine changes in fibrosis and the frequency of histological cirrhosis in corticosteroid-treated autoimmune hepatitis (AIH)...

..Progression is associated with HLA DR3/DR4 and worsening histological activity. Exacerbations or persistence of disease activity does not increase disease progression after treatment has been instituted...

..They may be associated with non-disease-specific immune responses, but they do not define individuals with a distinctive clinical phenotype, associated mucosal diseases, or treatment outcome...

..Investigational therapies promise to target critical pathogenic mechanisms affecting immunocyte activation, autoantigen recognition, cytokine interactions, and regenerative activity...

..These additional MHC encoded genes and other non-MHC encoded genes may be important determinants of disease susceptibility and severity in type 1 autoimmune hepatitis...

..It may represent variant forms of diverse conditions, a transition stage, or a separate entity with varying manifestations...

..Our goals were to assess budesonide in patients with treatment-dependent autoimmune hepatitis and to determine if efficacy and safety justified a controlled trial...

..They may be coincidental findings associated with classic disease or weak expressions of a variant syndrome. In the absence of a cholestatic clinical syndrome, they do not compel a different management strategy...

..All patients are candidates for this outcome, and withdrawal of medication, even during maintenance schedules, is necessary to assess its likelihood...

..The mechanisms that perturb immunologic homeostasis in this human model of the classical disease must be studied more rigorously...

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..Bile duct injury is not a feature of classical autoimmune hepatitis (AIH), but it has been described in variant forms of the disease...

..To assess the outcomes of empiric therapy with mycophenolate mofetil in patients with autoimmune hepatitis...

..Transitions in clinical and genetic phenotypes occur after age > or = 40 years. Genetic susceptibilities may favor etiologic factors that are age-related...

..This review aims to demonstrate how recent insights into disease behavior and mechanisms and the availability of new drugs can be assimilated into evolving concepts of diagnosis and treatment...

..New immunosuppressive agents and site-specific interventions promise to improve care...

..Better prognostic indices, new immunosuppressive agents, and site-specific molecular interventions promise to improve care...

..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...

..Polymorphisms that control cytokine production can affect immunoregulation. The frequency and consequences of these polymorphisms in type 1 autoimmune hepatitis were determined...

..Pregnancy is usually well-tolerated by mother and foetus but requires protection against postpartum exacerbation. Special populations must be recognized and treated with tailored regimens...

..Their presence with RA at accession characterizes a subgroup with cirrhosis...

..Percent positivity is greater in men than women, and seropositivity identifies individuals who commonly relapse after drug withdrawal...

..They may be complementary to antinuclear antibodies and smooth muscle antibodies in diagnosis and management...

..Our goal was to refine treatment end point criteria so as to reduce the frequency of relapse after drug withdrawal...

..Women have HLA DR4 more commonly than men, but this difference relates to their higher frequency of non-DRB1*0401 DR4 alleles. Female gender may promote risk associated with different HLA DR4 alleles...

..The model for end-stage liver disease may be a useful instrument for identifying patients prone to this outcome...

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..Our goals were to determine whether relapse is associated with disease progression and whether treatment end points can be refined...

..We conclude that autoimmune hepatitis is a model by which to study the genetic bases of autoimmunity...

..The aim of this study was to examine the role of DQA and DQB alleles in determining the risk for and the age of onset and severity of CD in an American population...

..Antimitochondrial antibodies (AMA) can occur in autoimmune hepatitis, but their durability and prognostic significance are uncertain...

..Combined testing improves but does not eliminate deficiencies in sensitivity, predictability and durability...

..Conditions in which the histologic findings suggest the overlap of two disorders or are insufficient for designation as classic disease constitute the variant syndromes...

..We conclude that patients with shared genetic risk factors do not have characteristic features nor do they have overlap syndromes. DR4 may be protective against primary sclerosing cholangitis...

..Findings can then be integrated into a comprehensive knowledge base that may be applicable to other autoimmune diseases...

..Hepatocellular carcinoma (HCC) is an uncommon but serious occurrence in autoimmune hepatitis. Our objective was to determine predictors for this neoplasm to improve screening strategies...

..HLA-DR3- or HLA-DR4-positive recipients are at risk for recurrence regardless of donor HLA status...

..HLA DRB1*03-DRB1*04 combines both susceptibility factors for type-1 autoimmune hepatitis...

..HLA DR11 may be protective against the development of microsomal antibodies in Italian patients, whereas HLA DR4, HLA DR13, and the B8-DR3-DQ2 haplotype may be protective in North American patients...

..CONCLUSION: A reliable diagnosis of AIH can be made using a very simple diagnostic score. We propose the diagnosis of probable AIH at a cutoff point greater than 6 points and definite AIH 7 points or higher...

..Under these circumstances, genetic studies may be the most practical, low risk means to investigate the pathogenesis of type 1 AIH and many other autoimmune diseases...

..Over-interpretation is the major pitfall in the clinical application of the serological results. New autoantibodies will emerge as the search for target antigens and key pathogenic pathways continues...

..CONCLUSIONS: These results suggest that the analysis of the immunoprecipitated RNAs is the most useful, sensitive and specific method to detect anti-tRNP((ser)sec)/SLA/LP autoantibodies...

..CONCLUSION: Autoimmune hepatitis is an important diagnosis to consider in all patients with chronic hepatitis of undetermined cause...

..CD should be considered in all patients diagnosed with autoimmune cholangitis as a gluten-free diet may avoid the need for immunosuppressive therapy in affected patients...