Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitis

Autoimmune hepatitis; Complete biochemical response; Immunoglobulin G

Bibliographic Details
Authors: Díaz-González, Álvaro, Schregel, Ida, Carballo-Folgoso, Lorena, Álvarez-Navascués, Carmen, Frisancho-Morales, Enrique, Miquel, Mireia, Barreira, Ana, Riveiro-Barciela, Mar
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:dnet:recercat____::355d54d3a845d3145cc0e2026fb8c353
Online Access:http://hdl.handle.net/11351/14601
https://hdl.handle.net/11351/14601
Access Level:Open access
Keyword:Hepatitis crònica activa
Immunoglobulina G
DISEASES::Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis, Chronic::Hepatitis, Autoimmune
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin G
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis crónica::hepatitis autoinmune
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::isotipos de inmunoglobulinas::inmunoglobulina G
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitis
title Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitis
spellingShingle Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitis
Díaz-González, Álvaro
Hepatitis crònica activa
Immunoglobulina G
DISEASES::Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis, Chronic::Hepatitis, Autoimmune
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin G
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis crónica::hepatitis autoinmune
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::isotipos de inmunoglobulinas::inmunoglobulina G
title_short Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitis
title_full Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitis
title_fullStr Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitis
title_full_unstemmed Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitis
title_sort Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitis
dc.creator.none.fl_str_mv Díaz-González, Álvaro
Schregel, Ida
Carballo-Folgoso, Lorena
Álvarez-Navascués, Carmen
Frisancho-Morales, Enrique
Miquel, Mireia
Barreira, Ana
Riveiro-Barciela, Mar
author Díaz-González, Álvaro
author_facet Díaz-González, Álvaro
Schregel, Ida
Carballo-Folgoso, Lorena
Álvarez-Navascués, Carmen
Frisancho-Morales, Enrique
Miquel, Mireia
Barreira, Ana
Riveiro-Barciela, Mar
author_role author
author2 Schregel, Ida
Carballo-Folgoso, Lorena
Álvarez-Navascués, Carmen
Frisancho-Morales, Enrique
Miquel, Mireia
Barreira, Ana
Riveiro-Barciela, Mar
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Díaz-González Á] Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases Group, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Santander, Spain. [Schregel I] Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. European Reference Network on Hepatological Diseases (ERN RARE-LIVER). [Carballo L, Álvarez-Navascués C] Digestive Diseases Department, Hospital Universitario Central de Asturias, Oviedo, Spain. [Frisancho-Morales E, Miquel M] Liver Unit, Digestive Diseases Department, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain. [Barreira-Díaz A, Riveiro-Barciela M] European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Servei d’Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Hepatitis crònica activa
Immunoglobulina G
DISEASES::Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis, Chronic::Hepatitis, Autoimmune
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin G
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis crónica::hepatitis autoinmune
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::isotipos de inmunoglobulinas::inmunoglobulina G
topic Hepatitis crònica activa
Immunoglobulina G
DISEASES::Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis, Chronic::Hepatitis, Autoimmune
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin G
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis crónica::hepatitis autoinmune
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::isotipos de inmunoglobulinas::inmunoglobulina G
description Autoimmune hepatitis; Complete biochemical response; Immunoglobulin G
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11351/14601
https://hdl.handle.net/11351/14601
url http://hdl.handle.net/11351/14601
https://hdl.handle.net/11351/14601
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv JHEP Reports;7(11)
https://doi.org/10.1016/j.jhepr.2025.101562
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412966947880960
spelling Isolated IgG elevation in patients with persistently normal transaminases does not affect the outcome of autoimmune hepatitisDíaz-González, ÁlvaroSchregel, IdaCarballo-Folgoso, LorenaÁlvarez-Navascués, CarmenFrisancho-Morales, EnriqueMiquel, MireiaBarreira, AnaRiveiro-Barciela, MarHepatitis crònica activaImmunoglobulina GDISEASES::Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis, Chronic::Hepatitis, AutoimmuneCHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin GENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis crónica::hepatitis autoinmuneCOMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::isotipos de inmunoglobulinas::inmunoglobulina GAutoimmune hepatitis; Complete biochemical response; Immunoglobulin GHepatitis autoinmune; Respuesta bioquímica completa; Inmunoglobulina GHepatitis autoimmune; Resposta bioquímica completa; Immunoglobulina GBackground & aims: The goal of treatment for autoimmune hepatitis is to achieve a complete biochemical response, defined as normalization of transaminases and immunoglobulin G (IgG) levels. Recent data suggest that IgG normalization does not significantly affect survival. We evaluated the impact of persistently elevated IgG levels (IgGe) and IgG flares (IgGf) on fibrosis progression and cirrhosis development. Methods: This retrospective multicenter cohort study included 493 patients with autoimmune hepatitis and persistently normal transaminase levels during follow-up. The inverse probability of treatment weighting (IPTW) propensity score method was used to balance the cohorts. Results: Three hundred forty-nine (70.8%) patients had persistently normal IgG (IgGn) levels, 89 (18.1%) had IgGe, and 55 (11.1%) had IgGf during follow-up. After a median follow-up of 6.2 years (IQR 4.1-10.1 years) with normal transaminase levels, median liver stiffness measurement (LSM) values remained stable, with no significant differences between groups. During the follow-up, 24 patients developed cirrhosis. Predictive factors for cirrhosis were age (hazard ratio [HR] 1.10, p <0.001), albumin (HR 0.20, p <0.001), IgG (HR 1.00, p = 0.001), and platelet count (HR 0.99, p = 0.001) at diagnosis; LSM (HR 1.30, p <0.001) at transaminase normalization; and transaminase normalization at 6 months (HR 0.24, p = 0.025). In the multivariate analysis, only LSM was independently associated with a higher risk of developing cirrhosis. After IPTW application, elevated IgG (IgGe or IgGf) did not affect fibrosis progression (p = 0.275) or cirrhosis development (p = 0.211). Conclusions: Persistent or temporary serum IgG elevation in patients with normal transaminase levels did not significantly affect autoimmune hepatitis disease progression, thus challenging the current definition of complete biochemical response. Impact and implications: The body of evidence showing a lesser impact of immunoglobulin G (IgG)values on outcomes in patients with autoimmune hepatitis (AIH) is growing. However, there is still a lack of robust information on the long-term outcomes, especially in patients who achieve persistent transaminase normalization. Persistently elevated IgG or IgG flares in patients with persistently normal transaminases do not seem to affect outcomes in patients with AIH. These results challenge the current definition of complete biochemical response in patients with AIH. Transaminase level normalization appeared to be the best treatment endpoint.MCL received support from the Instituto de Salud Carlos III (ISCIII) through the project ‘PI21/00800’ co-funded by the European Union and ‘Beca de Intensificación para Investigadores’ by the Spanish Association of the Study of the Liver (AEEH). IO was funded by Contractes Clínic de Recerca ‘Emili Letang—Josep Font’ 2022, granted by the Hospital Clínic Barcelona. BE was supported by the PRACTIS—Clinician Scientist program of Hannover Medical School, funded by the German Research Foundation (DFG, ME 3696/3). ADG received support from the Instituto de Investigación Valdecilla through the project ‘NVAL 21-10’.ElsevierInstitut Català de la Salut[Díaz-González Á] Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases Group, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Santander, Spain. [Schregel I] Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. European Reference Network on Hepatological Diseases (ERN RARE-LIVER). [Carballo L, Álvarez-Navascués C] Digestive Diseases Department, Hospital Universitario Central de Asturias, Oviedo, Spain. [Frisancho-Morales E, Miquel M] Liver Unit, Digestive Diseases Department, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain. [Barreira-Díaz A, Riveiro-Barciela M] European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Servei d’Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202620262025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/11351/14601https://hdl.handle.net/11351/14601Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésJHEP Reports;7(11)https://doi.org/10.1016/j.jhepr.2025.101562Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:recercat____::355d54d3a845d3145cc0e2026fb8c3532026-05-29T05:05:01Z
score 15,811543

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