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

International Autoimmune Hepatitis Group (IAIHG)

Research output: Contribution to journalArticlepeer-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 languageEnglish
Pages (from-to)84-97
Number of pages14
JournalJournal of Hepatology
Volume77
Issue number1
Early online date8 Feb 2022
DOIs
Publication statusPublished - 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

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