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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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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. |
format | Online Article Text |
id | pubmed-5266689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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