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Albert J Czaja - One of the best experts on this subject based on the ideXlab platform.
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Current concepts in Autoimmune Hepatitis.
Annals of Hepatology, 2020Co-Authors: Albert J CzajaAbstract: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. Sitespecific 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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Targeting Hepatic Fibrosis in Autoimmune Hepatitis
Digestive Diseases and Sciences, 2016Co-Authors: Aldo J. Montano-loza, Ragesh B. Thandassery, Albert J CzajaAbstract:Hepatic fibrosis develops or progresses in 25 % of patients with Autoimmune Hepatitis despite corticosteroid therapy. Current management regimens lack reliable noninvasive methods to assess changes in hepatic fibrosis and interventions that disrupt fibrotic pathways. The goals of this review are to indicate promising noninvasive methods to monitor hepatic fibrosis in Autoimmune Hepatitis and identify anti-fibrotic interventions that warrant evaluation. Laboratory methods can differentiate cirrhosis from non-cirrhosis, but their accuracy in distinguishing changes in histological stage is uncertain. Radiological methods include transient elastography, acoustic radiation force impulse imaging, and magnetic resonance elastography. Methods based on ultrasonography are comparable in detecting advanced fibrosis and cirrhosis, but their performances may be compromised by hepatic inflammation and obesity. Magnetic resonance elastography has excellent performance parameters for all histological stages in diverse liver diseases, is uninfluenced by inflammatory activity or body habitus, has been superior to other radiological methods in nonalcoholic fatty liver disease, and may emerge as the preferred instrument to evaluate fibrosis in Autoimmune Hepatitis. Promising anti-fibrotic interventions are site- and organelle-specific agents, especially inhibitors of nicotinamide adenine dinucleotide phosphate oxidases, transforming growth factor beta, inducible nitric oxide synthase, lysyl oxidases, and C–C chemokine receptors types 2 and 5. Autoimmune Hepatitis has a pro-fibrotic propensity, and noninvasive radiological methods, especially magnetic resonance elastography, and site- and organelle-specific interventions, especially selective antioxidants and inhibitors of collagen cross-linkage, may emerge to strengthen current management strategies.
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Transitioning from Idiopathic to Explainable Autoimmune Hepatitis
Digestive Diseases and Sciences, 2015Co-Authors: Albert J CzajaAbstract:Autoimmune Hepatitis lacks an identifiable cause, and its diagnosis requires the exclusion of etiologically defined diseases that resemble it. Insights into its pathogenesis are moving Autoimmune Hepatitis from an idiopathic to explainable disease, and the goal of this review is to describe the insights that are hastening this transition. Two types of Autoimmune Hepatitis are justified by serological markers, but they also have distinctive genetic associations ( DRB1 and DQB1 genes ) and autoantigens. DRB1 alleles are the principal susceptibility factors in white adults, and a six amino acid sequence encoded in the antigen-binding groove of class II molecules of the major histocompatibility complex can influence the selection of autoantigens. Polymorphisms, including variants of SH2B3 and CARD10 genes, may affect immune reactivity and disease severity. The cytochrome mono-oxygenase, CYP2D6, is the autoantigen associated with type 2 Autoimmune Hepatitis, and it shares homologies with multiple viruses that might promote self-intolerance by molecular mimicry. Chemokines, especially CXCL9 and CXCL10, orchestrate the migration of effector cells to sites of injury and are associated with disease severity. Cells of the innate and adaptive immune responses promote tissue damage, and possible deficiencies in the number and function of regulatory T cells may facilitate the injurious process. Receptor-mediated apoptosis is the principal mechanism of hepatocyte loss, and cell-mediated and antibody-dependent mechanisms of cytotoxicity also contribute. Insights that explain Autoimmune Hepatitis will allow triggering exogenous antigens to be characterized, risk management to be improved, prognostic indices to be refined, and site-specific therapeutic interventions to emerge.
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Targeting Apoptosis in Autoimmune Hepatitis
Digestive Diseases and Sciences, 2014Co-Authors: Albert J CzajaAbstract:Apoptosis is the predominant mechanism of liver cell death in Autoimmune Hepatitis, and interventions that can modulate this activity are emerging. The aim of this review was to describe the apoptotic mechanisms, possible aberrations, and opportunities for intervention in Autoimmune Hepatitis. Studies cited in PubMed from 1972 to 2014 for Autoimmune Hepatitis, apoptosis in liver disease, apoptosis mechanisms, and apoptosis treatment were examined. Apoptosis is overactive in Autoimmune Hepatitis, and the principal pathway of cell death is receptor mediated. Surface death receptors are activated by extrinsic factors including liver-infiltrating cytotoxic T cells and the cytokine milieu. The executioner caspases 3 and 7 cleave nuclear deoxyribonucleic acid, and the release of apoptotic bodies can stimulate inflammatory, immune, and fibrotic responses. Changes in mitochondrial membrane permeability can be initiated by caspase 8, and an intrinsic pathway of apoptosis can complement the extrinsic pathway. Defects in the apoptosis of activated effector cells can prolong their survival and sustain the immune response. Caspase inhibitors have been used in diverse experimental and human diseases to retard apoptosis. Oligonucleotides that inhibit the signaling of toll-like receptors can limit the presentation of auto-antigens, and inhibitors of apoptosis that extend the survival of effector cells can be blocked by antisense oligonucleotides. Mechanisms that enhance the clearance of apoptotic bodies and affect key signaling pathways are also feasible. Interventions that influence the survival of liver and effector cells by altering their apoptosis are candidates for study in Autoimmune Hepatitis.
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Cholestatic phenotypes of Autoimmune Hepatitis.
Clinical Gastroenterology and Hepatology, 2013Co-Authors: Albert J CzajaAbstract:Autoimmune Hepatitis can have cholestatic features that are outside the codified diagnostic criteria. These features have uncertain effects on the clinical presentation and progression of disease. Patients with Autoimmune Hepatitis can have antimitochondrial antibodies and coincidental bile duct injury or loss (2%–13% of patients), focal biliary strictures and dilations based on cholangiography (2%–11%), or histologic changes of bile duct injury or loss in the absence of other features (5%–11%). These findings probably represent atypical manifestations of Autoimmune Hepatitis or variants of primary biliary cirrhosis or primary sclerosing cholangitis, depending on the predominant findings. Serum levels of alkaline phosphatase and γ-glutamyl transferase, histologic features of bile duct injury, and findings from cholangiography are associated with responsiveness to corticosteroid therapy and individualized alternative treatments. Corticosteroid therapy, in combination with low-dose ursodeoxycholic acid, has been promulgated by international societies, but these recommendations are not based on strong evidence. The frequency, variable outcomes, and uncertainties in diagnosis and management of the cholestatic phenotypes must be addressed by a collaborative investigational network. This network should define the genetic and pathologic features of these disorders, standardize their nomenclature, and establish a treatment algorithm. In this review, the different cholestatic phenotypes of Autoimmune Hepatitis, mechanisms of pathogenesis, current management strategies and outcomes, and opportunities for improving understanding and therapy are presented.
Meral Akdogan - One of the best experts on this subject based on the ideXlab platform.
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ornidazole induced Autoimmune Hepatitis
European Journal of Gastroenterology & Hepatology, 2001Co-Authors: Y Kosar, Nurgul Sasmaz, P Oguz, Sabite Kacar, E Erden, Erkan Parlak, Meral AkdoganAbstract:Ornidazole is a commonly prescribed antiparasitic drug for parasitic infestations, including amoebiasis, giardiasis and Trichomonas vaginalis. Several cases of antibiotic-induced Autoimmune Hepatitis (AIH) or AIH-like syndrome have been reported recently. In this report, we describe a 35-year-old woman with two relapses of AIH induced by ornidazole prescribed for diarrhoea and vaginal infection.
Y Kosar - One of the best experts on this subject based on the ideXlab platform.
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ornidazole induced Autoimmune Hepatitis
European Journal of Gastroenterology & Hepatology, 2001Co-Authors: Y Kosar, Nurgul Sasmaz, P Oguz, Sabite Kacar, E Erden, Erkan Parlak, Meral AkdoganAbstract:Ornidazole is a commonly prescribed antiparasitic drug for parasitic infestations, including amoebiasis, giardiasis and Trichomonas vaginalis. Several cases of antibiotic-induced Autoimmune Hepatitis (AIH) or AIH-like syndrome have been reported recently. In this report, we describe a 35-year-old woman with two relapses of AIH induced by ornidazole prescribed for diarrhoea and vaginal infection.
Diego Vergani - One of the best experts on this subject based on the ideXlab platform.
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pathogenesis of Autoimmune Hepatitis
Best Practice & Research in Clinical Gastroenterology, 2011Co-Authors: Maria Serena Longhi, Rodrigo Liberal, Giorgina Mielivergani, Diego VerganiAbstract:The mechanisms underlying the pathogenesis of Autoimmune Hepatitis are not fully understood, though there is growing evidence that genetic predisposition, molecular mimicry and/or impairment of regulatory T-cells are involved in the initiation and perpetuation of the Autoimmune liver attack. The histological picture of interface Hepatitis, characterized by a dense portal mononuclear cell infiltrate, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of this condition. Liver damage is likely to be orchestrated by CD4 pos T-cells recognizing an autoantigenic liver peptide. For autoimmunity to arise, the peptide must be presented by antigen-presenting cells to naive CD4 pos T-helper (Th0) cells. Once activated, Th0-cells can differentiate into Th1-, Th2-, or Th17-cells, initiating a cascade of immune reactions that are determined by the cytokines they produce. Autoantigen recognition and the above effector mechanisms are opposed by regulatory T-cells, a cell subset numerically and functionally impaired in Autoimmune Hepatitis.
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Autoimmune Hepatitis after liver transplantation.
Clinical Gastroenterology and Hepatology, 2011Co-Authors: Rodrigo Liberal, Maria Serena Longhi, Charlotte R. Grant, Giorgina Mieli–vergani, Diego VerganiAbstract:Liver transplantation is an effective treatment for patients with end-stage acute and chronic Autoimmune Hepatitis. However, despite the good outcomes reported, disease recurrence is relatively common in the allograft. In addition, autoimmunity and Autoimmune liver disease can arise de novo after transplantation for non-Autoimmune liver disorders. Little is known about the mechanisms by which Autoimmune diseases develop after liver transplantation, but genetic factors, molecular mimicry, impaired regulatory T-cell responses, and exposures to new alloantigens might be involved. Regardless of the pathogenic mechanisms, it is important to remain aware of the existence of recurrent and de novo Autoimmune Hepatitis after liver transplantation; these disorders are similar to classic Autoimmune Hepatitis and are therefore not treated with standard antirejection strategies.
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Pharmacological management of Autoimmune Hepatitis
Expert Opinion on Pharmacotherapy, 2011Co-Authors: Diego Vergani, Giorgina Mieli-verganiAbstract:Introduction: Without prompt immunosuppressive treatment, Autoimmune Hepatitis is a devastating, albeit rare, liver disease. It affects both adults and children, being particularly aggressive in the latter. Eighty per cent of patients respond satisfactorily to treatment; the other 20% progress to end-stage liver disease and require transplantation. Areas covered: This review emphasizes the importance of a timely diagnosis of Autoimmune Hepatitis and provides a practical guide for its treatment. The authors summarize the treatment options available for Autoimmune Hepatitis and stress that most patients respond successfully to standard treatment with prednisolone and azathioprine, two well-tried and inexpensive drugs. The authors also review the options for difficult-to-treat patients (non-responders and frequent relapsers), for whom newer immunosuppressive agents – usually employed as anti-rejection drugs – have been tried with variable success. Expert opinion: Autoimmune Hepatitis is exquisitely responsiv...
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Cutting Edge Issues in Autoimmune Hepatitis
Clinical Reviews in Allergy & Immunology, 2011Co-Authors: Diego Vergani, Giorgina Mieli-verganiAbstract:Autoimmune Hepatitis is an inflammatory liver disease affecting mainly females and characterised histologically by interface Hepatitis, biochemically by elevated transaminase levels and serologically by circulating autoantibodies and increased levels of immunoglobulin G. Autoimmune Hepatitis responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Seropositivity for smooth muscle and/or antinuclear antibody defines type 1 Autoimmune Hepatitis, while positivity for liver kidney microsomal type 1 antibody defines type 2 Autoimmune Hepatitis. The aetiology of Autoimmune Hepatitis is unknown, though both genetic and environmental factors are involved in its expression. The major mechanism of liver damage involves immune reactions against host liver antigens that are not adequately controlled by defective regulatory T cells. Current research aiming at potentiating regulatory T cell function in vitro to reconstitute tolerance in vivo has given promising results.
Ansgar W. Lohse - One of the best experts on this subject based on the ideXlab platform.
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Diagnostic Criteria for Autoimmune Hepatitis: Scores and More
Digestive Diseases, 2015Co-Authors: Ansgar W. LohseAbstract:The diagnosis of Autoimmune Hepatitis is a clinical diagnosis that combines the patient's history, clinical examination, laboratory and serological markers and the results of a liver biopsy. As the clinical spectrum of Autoimmune Hepatitis is very wide, making the diagnosis can sometimes be difficult, especially in non-expert hands. Diagnostic scores can help in making the diagnosis, and the simplified diagnostic score of the International Autoimmune Hepatitis Group has a sensitivity and specificity of around 90% in the different populations that have been studied. Therefore, it can be very helpful in everyday use, but nonetheless for some patients the score is not good enough. Limitations are patients with very acute presentations as well as atypical cases. In such cases, a trial of monotherapy with steroids and quick tapering of the steroids is recommended. If the disease responds well to treatment, but recurs after tapering the steroids, the diagnosis of Autoimmune Hepatitis is confirmed. In addition to its clinical use, diagnostic scores can also be helpful in defining the unified criteria in order to make scientific studies comparable.
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Diagnostic criteria for Autoimmune Hepatitis
Best Practice & Research in Clinical Gastroenterology, 2011Co-Authors: Ansgar W. Lohse, C WiegardAbstract:The clinical spectrum of Autoimmune Hepatitis is very wide. In addition, Autoimmune Hepatitis can present in any age group. Diagnosis is usually made by a combination of clinical, laboratory and histological features. Diagnostic scores can help both in the daily diagnostic work-up of patients, and in allowing comparability of clinical scientific studies. However, all diagnostic scores have limitations in individual cases, which are discussed in this review.
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The revised international Autoimmune Hepatitis score in chronic liver diseases including Autoimmune Hepatitis/overlap syndromes and Autoimmune Hepatitis with concurrent other liver disorders
Journal of Autoimmune Diseases, 2007Co-Authors: Panagiotis Papamichalis, Kalliopi Zachou, George K. Koukoulis, Aikaterini Veloni, Efthimia G Karacosta, Lampros Kypri, Ioannis Mamaloudis, Stella Gabeta, Eirini I. Rigopoulou, Ansgar W. LohseAbstract:Background We conducted a study in order to determine the usefulness and diagnostic value of International Autoimmune Hepatitis Group (IAHG) score in non-Autoimmune Hepatitis (AIH) hepatic disorders as well as in AIH/overlap syndromes and in cases with coexistence of AIH and other liver diseases.
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Autoantibodies in experimental Autoimmune Hepatitis
Journal of Hepatology, 1992Co-Authors: Ansgar W. Lohse, Silvia Brunner, A. Kyriatsoulis, Michael Manns, Karl-hermann Meyer Zum BüschenfeldeAbstract:Abstract Experimental Autoimmune Hepatitis (EAH) can be induced in mice by immunization with syngeneic soluble liver antigens in complete Freund's adjuvant. It has previously been shown that autoreactive T cells play an important role in this animal model of Autoimmune Hepatitis. We have studied the occurrence of liver autoantibodies in EAH. Characteristic autoantibodies appeared several weeks after disease induction and antibody titres continued to rise when histological and biochemical signs of disease activity had already regressed. Autoantibodies in EAH seemed to recognize autoantigens other than those present in Autoimmune chronic active Hepatitis patients. We conclude that autoantibodies arise in experimental Autoimmune Hepatitis but that these autoantibodies do not play a critical role in the pathogenesis of the disease.
