Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation

International Autoimmune Hepatitis Group (IAIHG)

doi:10.1016/j.jhep.2022.01.022

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation

International Autoimmune Hepatitis Group (IAIHG)

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.

METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis.

RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001).

CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH.

LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

Original language	English
Pages (from-to)	84-97
Number of pages	14
Journal	Journal of Hepatology
Volume	77
Issue number	1
Early online date	8 Feb 2022
DOIs	https://doi.org/10.1016/j.jhep.2022.01.022
Publication status	Published - Jul 2022

Bibliographical note

Financial support:
Aldo J. Montano-Loza receives funding from the University of Alberta Hospital Foundation (UHF) and the Canadian Liver Foundation (CLF). Maryam Ebadi receives funding from the Canadian Institutes of Health Research (CIHR) - Institute of Nutrition, Metabolism,and Diabetes (INMD) Fellowship–Hepatology, in partnership with the Canadian Association for the Study of the Liver (CASL) and the Canadian Liver Foundation (CLF). Ye Htun Oo receives funding from Sir Jules Thorn Biomedical Research Award, Transbioline Innovative Medicine Initiatives, Medical Research Foundation, MRC, Queen Elizabeth Hospital Birmingham Charity and EASL. Vincenzo Ronca receives funding from EASL Juan Rodes PhD fellowship programme.

Copyright:
© 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Keywords

Adult
Female
Hepatitis, Autoimmune
Humans
Immunoglobulin G
Immunosuppressive Agents/therapeutic use
Liver Transplantation/adverse effects
Male
Mycophenolic Acid/therapeutic use
Recurrence
Risk Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

@article{5b5fd24453964c808b25cd2f9088b016,

title = "Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation",

abstract = "BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis.RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001).CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH.LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.",

keywords = "Adult, Female, Hepatitis, Autoimmune, Humans, Immunoglobulin G, Immunosuppressive Agents/therapeutic use, Liver Transplantation/adverse effects, Male, Mycophenolic Acid/therapeutic use, Recurrence, Risk Factors",

author = "{International Autoimmune Hepatitis Group (IAIHG)} and Montano-Loza, {Aldo J.} and Vincenzo Ronca and Maryam Ebadi and Hansen, {Bettina E.} and Gideon Hirschfield and Saleh Elwir and Mohamad Alsaed and Piotr Milkiewicz and Janik, {Maciej K.} and Hanns-Ulrich Marschall and Burza, {Maria Antonella} and Cumali Efe and Calı{\c s}kan, {Ali Rıza} and Murat Harputluoglu and G{\"o}khan Kaba{\c c}am and D{\'e}bora Terrabuio and {De Quadros Onofrio}, Fernanda and Nazia Selzner and Alan Bonder and Albert Par{\'e}s and Laura Llovet and Murat Akyıldız and Cigdem Arikan and Manns, {Michael P} and Richard Taubert and Anna-Lena Weber and Schiano, {Thomas D.} and Brandy Haydel and Piotr Czubkowski and Piotr Socha and Natalia O{\l}dak and Nobuhisa Akamatsu and Atsushi Tanaka and Cynthia Levy and Martin, {Eric F.} and Aparna Goel and Mai Sedki and Irena Jankowska and Toru Ikegami and Maria Rodriguez and Martina Sterneck and Christina Weiler-Normann and Christoph Schramm and Donato, {Maria Francesca} and Ansgar Lohse and Andrade, {Ra{\'u}l J.} and Patwardhan, {Vilas R.} and {van Hoek}, Bart and Maaike Biewenga and Oo, {Ye htun}",

note = "Financial support: Aldo J. Montano-Loza receives funding from the University of Alberta Hospital Foundation (UHF) and the Canadian Liver Foundation (CLF). Maryam Ebadi receives funding from the Canadian Institutes of Health Research (CIHR) - Institute of Nutrition, Metabolism,and Diabetes (INMD) Fellowship–Hepatology, in partnership with the Canadian Association for the Study of the Liver (CASL) and the Canadian Liver Foundation (CLF). Ye Htun Oo receives funding from Sir Jules Thorn Biomedical Research Award, Transbioline Innovative Medicine Initiatives, Medical Research Foundation, MRC, Queen Elizabeth Hospital Birmingham Charity and EASL. Vincenzo Ronca receives funding from EASL Juan Rodes PhD fellowship programme. Copyright: {\textcopyright} 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",

year = "2022",

month = jul,

doi = "10.1016/j.jhep.2022.01.022",

language = "English",

volume = "77",

pages = "84--97",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "Elsevier",

number = "1",

}

TY - JOUR

T1 - Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation

AU - International Autoimmune Hepatitis Group (IAIHG)

AU - Montano-Loza, Aldo J.

AU - Ronca, Vincenzo

AU - Ebadi, Maryam

AU - Hansen, Bettina E.

AU - Hirschfield, Gideon

AU - Elwir, Saleh

AU - Alsaed, Mohamad

AU - Milkiewicz, Piotr

AU - Janik, Maciej K.

AU - Marschall, Hanns-Ulrich

AU - Burza, Maria Antonella

AU - Efe, Cumali

AU - Calışkan, Ali Rıza

AU - Harputluoglu, Murat

AU - Kabaçam, Gökhan

AU - Terrabuio, Débora

AU - De Quadros Onofrio, Fernanda

AU - Selzner, Nazia

AU - Bonder, Alan

AU - Parés, Albert

AU - Llovet, Laura

AU - Akyıldız, Murat

AU - Arikan, Cigdem

AU - Manns, Michael P

AU - Taubert, Richard

AU - Weber, Anna-Lena

AU - Schiano, Thomas D.

AU - Haydel, Brandy

AU - Czubkowski, Piotr

AU - Socha, Piotr

AU - Ołdak, Natalia

AU - Akamatsu, Nobuhisa

AU - Tanaka, Atsushi

AU - Levy, Cynthia

AU - Martin, Eric F.

AU - Goel, Aparna

AU - Sedki, Mai

AU - Jankowska, Irena

AU - Ikegami, Toru

AU - Rodriguez, Maria

AU - Sterneck, Martina

AU - Weiler-Normann, Christina

AU - Schramm, Christoph

AU - Donato, Maria Francesca

AU - Lohse, Ansgar

AU - Andrade, Raúl J.

AU - Patwardhan, Vilas R.

AU - van Hoek, Bart

AU - Biewenga, Maaike

AU - Oo, Ye htun

N1 - Financial support: Aldo J. Montano-Loza receives funding from the University of Alberta Hospital Foundation (UHF) and the Canadian Liver Foundation (CLF). Maryam Ebadi receives funding from the Canadian Institutes of Health Research (CIHR) - Institute of Nutrition, Metabolism,and Diabetes (INMD) Fellowship–Hepatology, in partnership with the Canadian Association for the Study of the Liver (CASL) and the Canadian Liver Foundation (CLF). Ye Htun Oo receives funding from Sir Jules Thorn Biomedical Research Award, Transbioline Innovative Medicine Initiatives, Medical Research Foundation, MRC, Queen Elizabeth Hospital Birmingham Charity and EASL. Vincenzo Ronca receives funding from EASL Juan Rodes PhD fellowship programme. Copyright: © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2022/7

Y1 - 2022/7

N2 - BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis.RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001).CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH.LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

AB - BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis.RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001).CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH.LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

KW - Adult

KW - Female

KW - Hepatitis, Autoimmune

KW - Humans

KW - Immunoglobulin G

KW - Immunosuppressive Agents/therapeutic use

KW - Liver Transplantation/adverse effects

KW - Male

KW - Mycophenolic Acid/therapeutic use

KW - Recurrence

KW - Risk Factors

U2 - 10.1016/j.jhep.2022.01.022

DO - 10.1016/j.jhep.2022.01.022

M3 - Article

C2 - 35143897

SN - 0168-8278

VL - 77

SP - 84

EP - 97

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 1

ER -

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation

Abstract

Bibliographical note

Keywords

UN SDGs

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