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Novel Immunotherapies for Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive...

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Autores principales: Cassim, Shamir, Bilodeau, Marc, Vincent, Catherine, Lapierre, Pascal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266689/
https://www.ncbi.nlm.nih.gov/pubmed/28184367
http://dx.doi.org/10.3389/fped.2017.00008
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author Cassim, Shamir
Bilodeau, Marc
Vincent, Catherine
Lapierre, Pascal
author_facet Cassim, Shamir
Bilodeau, Marc
Vincent, Catherine
Lapierre, Pascal
author_sort Cassim, Shamir
collection PubMed
description Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4(+) T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects.
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spelling pubmed-52666892017-02-09 Novel Immunotherapies for Autoimmune Hepatitis Cassim, Shamir Bilodeau, Marc Vincent, Catherine Lapierre, Pascal Front Pediatr Pediatrics Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4(+) T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects. Frontiers Media S.A. 2017-01-26 /pmc/articles/PMC5266689/ /pubmed/28184367 http://dx.doi.org/10.3389/fped.2017.00008 Text en Copyright © 2017 Cassim, Bilodeau, Vincent and Lapierre. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Cassim, Shamir
Bilodeau, Marc
Vincent, Catherine
Lapierre, Pascal
Novel Immunotherapies for Autoimmune Hepatitis
title Novel Immunotherapies for Autoimmune Hepatitis
title_full Novel Immunotherapies for Autoimmune Hepatitis
title_fullStr Novel Immunotherapies for Autoimmune Hepatitis
title_full_unstemmed Novel Immunotherapies for Autoimmune Hepatitis
title_short Novel Immunotherapies for Autoimmune Hepatitis
title_sort novel immunotherapies for autoimmune hepatitis
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266689/
https://www.ncbi.nlm.nih.gov/pubmed/28184367
http://dx.doi.org/10.3389/fped.2017.00008
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