Autoimmune Liver Disease And Rheumatic Manifestations
Autoimmune Liver Disease And Rheumatic Manifestations
Purpose of Review: To review studies that clarify the rheumatic manifestations of autoimmune hepatitis, elucidate shared pathogenic pathways, and encourage innovative site-specific therapies.
Recent Findings: Autoimmune hepatitis has clinical manifestations, serological markers, pathogenic mechanisms, genetic predispositions, and therapies similar to the rheumatic diseases. The rheumatic manifestations may mask the underlying liver disease and vice versa. Variations in clinical phenotype and outcome for the autoimmune liver diseases may reflect host-specific and region-specific factors, and defects in counter-regulatory suppressor functions by regulatory T cells may facilitate cell-mediated cytotoxicity and autoreactivity. Mixed syndromes with hallmark features of one disease in another probably reflect a genetic predisposition for immune expression that is shared among the diseases. Mycophenolate mofetil, budesonide, rapamycin, and 6-thioguanine are promising treatments, and de-novo autoimmune hepatitis after liver transplantation suggests that the calcineurin inhibitors may have paradoxical effects on self-tolerance.
Summary: Clinical phenotypes of autoimmune hepatitis commonly include rheumatic manifestations that can mask the liver disease. Defects in counter-regulatory functions enhance cell-mediated cytotoxicity, and pharmacological interventions that promise site-specific actions affecting immunocyte differentiation and proliferation are feasible.
Rheumatic features are common in autoimmune liver disease, and they justified early efforts to assimilate autoimmune hepatitis into the diagnosis of systemic lupus erythematosus. Hypotheses of pathogenesis have been similar between the rheumatic and autoimmune liver diseases, and initial treatment strategies for autoimmune hepatitis were based on the same medications used in the rheumatic disorders. Current proposals to evaluate monoclonal antibodies, oral tolerance regimens, and competing synthetic peptides in the treatment of immune-mediated liver disease are founded on initiatives tested in the rheumatic diseases.
Autoimmune hepatitis is separate from the rheumatic conditions, but the boundaries between the disorders can be indistinct. Over 30% of patients with autoimmune hepatitis have concurrent immune-mediated manifestations, and the rheumatic features in these patients may mask the underlying liver disease. In contrast, 25% of patients with primary rheumatic conditions have coincidental liver dysfunction, and they may be misclassified and treated as primary liver disease.
The goals of this report are to review recent studies that clarify the rheumatic manifestations of autoimmune hepatitis, elucidate pathogenic pathways that may be common to both conditions, and encourage the emergence of innovative site-specific therapies that have broad application. Progress in the therapeutics of the autoimmune diseases depends on continued cross-talk between the various disciplines and the acquisition of knowledge derived from all clinical arenas.
Purpose of Review: To review studies that clarify the rheumatic manifestations of autoimmune hepatitis, elucidate shared pathogenic pathways, and encourage innovative site-specific therapies.
Recent Findings: Autoimmune hepatitis has clinical manifestations, serological markers, pathogenic mechanisms, genetic predispositions, and therapies similar to the rheumatic diseases. The rheumatic manifestations may mask the underlying liver disease and vice versa. Variations in clinical phenotype and outcome for the autoimmune liver diseases may reflect host-specific and region-specific factors, and defects in counter-regulatory suppressor functions by regulatory T cells may facilitate cell-mediated cytotoxicity and autoreactivity. Mixed syndromes with hallmark features of one disease in another probably reflect a genetic predisposition for immune expression that is shared among the diseases. Mycophenolate mofetil, budesonide, rapamycin, and 6-thioguanine are promising treatments, and de-novo autoimmune hepatitis after liver transplantation suggests that the calcineurin inhibitors may have paradoxical effects on self-tolerance.
Summary: Clinical phenotypes of autoimmune hepatitis commonly include rheumatic manifestations that can mask the liver disease. Defects in counter-regulatory functions enhance cell-mediated cytotoxicity, and pharmacological interventions that promise site-specific actions affecting immunocyte differentiation and proliferation are feasible.
Rheumatic features are common in autoimmune liver disease, and they justified early efforts to assimilate autoimmune hepatitis into the diagnosis of systemic lupus erythematosus. Hypotheses of pathogenesis have been similar between the rheumatic and autoimmune liver diseases, and initial treatment strategies for autoimmune hepatitis were based on the same medications used in the rheumatic disorders. Current proposals to evaluate monoclonal antibodies, oral tolerance regimens, and competing synthetic peptides in the treatment of immune-mediated liver disease are founded on initiatives tested in the rheumatic diseases.
Autoimmune hepatitis is separate from the rheumatic conditions, but the boundaries between the disorders can be indistinct. Over 30% of patients with autoimmune hepatitis have concurrent immune-mediated manifestations, and the rheumatic features in these patients may mask the underlying liver disease. In contrast, 25% of patients with primary rheumatic conditions have coincidental liver dysfunction, and they may be misclassified and treated as primary liver disease.
The goals of this report are to review recent studies that clarify the rheumatic manifestations of autoimmune hepatitis, elucidate pathogenic pathways that may be common to both conditions, and encourage the emergence of innovative site-specific therapies that have broad application. Progress in the therapeutics of the autoimmune diseases depends on continued cross-talk between the various disciplines and the acquisition of knowledge derived from all clinical arenas.
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