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


Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
07 2022
Historique:
received: 06 05 2021
revised: 26 01 2022
accepted: 27 01 2022
pubmed: 11 2 2022
medline: 22 6 2022
entrez: 10 2 2022
Statut: ppublish

Résumé

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. 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. 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). 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 35143897
pii: S0168-8278(22)00067-8
doi: 10.1016/j.jhep.2022.01.022
pii:
doi:

Substances chimiques

Immunoglobulin G 0
Immunosuppressive Agents 0
Mycophenolic Acid HU9DX48N0T

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

84-97

Informations de copyright

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

Déclaration de conflit d'intérêts

Conflicts of interest These authors disclose the following: A.J. Montano-Loza has served on advisory boards for Intercept Pharmaceuticals. B.E. Hansen reports grants from Intercept Pharmaceuticals and Zambon Nederland B.V. and consulting work for Intercept Pharmaceuticals and Novartis. A.E. Kremer reports consulting work for CymaBay, GSK, Intercept Pharmaceuticals, and Mirum and grants from Intercept Pharmaceuticals. A. Parés consults for Intercept and Novartis. A. Floreani reports consulting activities for Intercept Pharmaceuticals. A. Mason consults for, is on the speakers' bureau of, and received grants from Intercept. He received grants from Merk. The remaining authors disclose no conflicts. Please refer to the accompanying ICMJE disclosure forms for further details.

Auteurs

Aldo J Montano-Loza (AJ)

Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada. Electronic address: montanol@ualberta.ca.

Vincenzo Ronca (V)

Center for Liver Research & NIHR Birmingham BRC, University of Birmingham & University Hospital Birmingham NHS Foundation Trust, Institute of Immunology and Immunotherapy, University of Birmingham, UK.

Maryam Ebadi (M)

Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada.

Bettina E Hansen (BE)

Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Canada.

Gideon Hirschfield (G)

Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Canada.

Saleh Elwir (S)

Baylor University Medical Center, Dallas, USA.

Mohamad Alsaed (M)

Baylor University Medical Center, Dallas, USA.

Piotr Milkiewicz (P)

Liver and Internal Medicine Unit, Medical University of Warsaw, Poland.

Maciej K Janik (MK)

Liver and Internal Medicine Unit, Medical University of Warsaw, Poland.

Hanns-Ulrich Marschall (HU)

Sahlgrenska University Hospital, Gothenburg, Sweden.

Maria Antonella Burza (MA)

Sahlgrenska University Hospital, Gothenburg, Sweden.

Cumali Efe (C)

Department of Gastroenterology, Harran University Hospital, Şanlıurfa, Turkey.

Ali Rıza Calışkan (AR)

Department of Gastroenterology, Inönü University School of Medicine, Malatya, Turkey.

Murat Harputluoglu (M)

Department of Gastroenterology, Inönü University School of Medicine, Malatya, Turkey.

Gökhan Kabaçam (G)

Clinic of Gastroenterology and Liver Transplantation, Guven Hospital Ankara, Turkey.

Débora Terrabuio (D)

Department of Gastroenterology - University of São Paulo School of Medicine, São Paulo, Brazil.

Fernanda de Quadros Onofrio (F)

Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Canada.

Nazia Selzner (N)

Toronto Center for Liver Disease, University Health Network, University of Toronto, Toronto, Canada.

Alan Bonder (A)

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.

Albert Parés (A)

Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

Laura Llovet (L)

Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

Murat Akyıldız (M)

Koç University School of Medicine, Department of Gastroenterology and Liver Transplantation Center, Istanbul, Turkey.

Cigdem Arikan (C)

Koc University School of Medicine, Pediatric Gastroenterology and Hepatology, Organ Transplantation Center, Koc University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey.

Michael P Manns (MP)

European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Department Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Richard Taubert (R)

European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Department Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Anna-Lena Weber (AL)

European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Department Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Thomas D Schiano (TD)

Recanati/Miller Transplantation Institute/Division of Liver Diseases, Mount Sinai Medical Center, New York, USA.

Brandy Haydel (B)

Recanati/Miller Transplantation Institute/Division of Liver Diseases, Mount Sinai Medical Center, New York, USA.

Piotr Czubkowski (P)

Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.

Piotr Socha (P)

Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.

Natalia Ołdak (N)

Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.

Nobuhisa Akamatsu (N)

University of Tokyo, Japan.

Atsushi Tanaka (A)

Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.

Cynthia Levy (C)

University of Miami Miller School of Medicine, Miami, USA.

Eric F Martin (EF)

University of Miami Miller School of Medicine, Miami, USA.

Aparna Goel (A)

Stanford University, Stanford, USA.

Mai Sedki (M)

Stanford University, Stanford, USA.

Irena Jankowska (I)

Children's Memorial Health Institute, Warsaw, Poland.

Toru Ikegami (T)

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Maria Rodriguez (M)

UKE Hamburg, Hamburg, Germany.

Martina Sterneck (M)

UKE Hamburg, Hamburg, Germany.

Christina Weiler-Normann (C)

UKE Hamburg, Hamburg, Germany.

Christoph Schramm (C)

UKE Hamburg, Hamburg, Germany.

Maria Francesca Donato (MF)

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Liver Tranplant Hepatology Unit, Division of Gastroenterology and Hepatology, Milan, Italy.

Ansgar Lohse (A)

University Medical Center, Hamburg, Germany.

Raul J Andrade (RJ)

Gastroenterology Service -IBIMA. University Hospital and CIBERehd. University of Málaga, Spain.

Vilas R Patwardhan (VR)

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.

Bart van Hoek (B)

Leiden University Medical Center, Leiden, Netherlands.

Maaike Biewenga (M)

Leiden University Medical Center, Leiden, Netherlands.

Andreas E Kremer (AE)

Department of Medicine, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland.

Yoshihide Ueda (Y)

Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Mark Deneau (M)

University of Utah, Salt Lake City, USA.

Mark Pedersen (M)

University of Texas Southwestern Medical Center, Dallas, USA.

Marlyn J Mayo (MJ)

University of Texas Southwestern Medical Center, Dallas, USA.

Annarosa Floreani (A)

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.

Patrizia Burra (P)

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.

Maria Francesca Secchi (MF)

University of Padova, Padova, Italy.

Benedetta Terziroli Beretta-Piccoli (BT)

Epatocentro Ticino & Università della Svizzera Italiana, Lugano, Switzerland.

Marco Sciveres (M)

UPMC Pediatric Liver Center, Palermo, Italy.

Giuseppe Maggiore (G)

Hepatogastroenterology, Nutrition and Liver Transplant IRCCS Bambino Gesù Pediatric Hospital, Rome, Italy.

Syed-Mohammed Jafri (SM)

Henry Ford Health System, Detroit, Michigan, USA.

Dominique Debray (D)

Pediatric Liver Unit, French National Reference Center for Rare Diseases BA and Genetic Cholestasis, Hôpital Necker, Université de Paris, Paris, France.

Muriel Girard (M)

Pediatric Liver Unit, French National Reference Center for Rare Diseases BA and Genetic Cholestasis, Hôpital Necker, Université de Paris, Paris, France.

Florence Lacaille (F)

Gastroenterology-Hepatology-Nutrition Unit, Hôpital Necker-Enfants Malades, Paris, France.

Ellina Lytvyak (E)

Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada.

Andrew L Mason (AL)

Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada.

Michael Heneghan (M)

King's College Hospital NHS Foundation Trust, London, UK.

Ye Htun Oo (YH)

Center for Liver and Gastro Research & National Institute of Health Research Birmingham Biomedical Research Centre, University of Birmingham; Centre for Rare Disease and ERN Rare Liver Centre, Liver Transplant and Hepatobiliary Unit, University Hospital Birmingham NHS Foundation Trust, UK. Electronic address: y.h.oo@bham.ac.uk.

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