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

Montano-Loza AJ, Ronca V, Ebadi M, Hansen BE, Hirschfield G, Elwir S, Alsaed M, Milkiewicz P, Janik MK, Marschall HU, Burza MA, Efe C, Calışkan AR, Harputluoglu M, Kabaçam G, Terrabuio D, de Quadros Onofrio F, Selzner N, Bonder A, Parés A, Llovet L, Akyıldız M, Arikan C, Manns MP, Taubert R, Weber AL, Schiano TD, Haydel B, Czubkowski P, Socha P, Ołdak N, Akamatsu N, Tanaka A, Levy C, Martin EF, Goel A, Sedki M, Jankowska I, Ikegami T, Rodriguez M, Sterneck M, Weiler-Normann C, Schramm C, Donato MF, Lohse A, Andrade RJ, Patwardhan VR, van Hoek B, Biewenga M, Kremer A, Ueda Y, Deneau M, Pedersen M, Mayo MJ, Floreani A, Burra P, Secchi MF, Beretta-Piccoli BT, Sciveres M, Maggiore G, Jafri SM, Debray D, Girard M, Lacaille F, Lytvyak E, Mason AL, Heneghan M, Oo YH (2022)

Publication Type: Journal article

Publication year: 2022

Journal

DOI: 10.1016/j.jhep.2022.01.022

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.

Authors with CRIS profile

Involved external institutions

University of Alberta Canada (CA) Harvard University United States (USA) (US) University of Miami United States (USA) (US) Universidad de Málaga / University of Malaga Spain (ES) Mount Sinai Health System United States (USA) (US) Harran Üniversitesi Turkey (TR) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset Sweden (SE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) Teikyo University Japan (JP) University Health Network (UHN) Canada (CA) Children's Memorial Health Institute / Instytut "Pomnik - Centrum Zdrowia Dziecka" Poland (PL) Baylor University Medical Center United States (USA) (US) Kyoto University / 京都大学 Kyōto daigaku Japan (JP) Inonu Univeristy Turkey (TR) University of São Paulo / Universidade de São Paulo (USP) Brazil (BR) Università della Svizzera italiana (USI) Switzerland (CH) Henry Ford Health System (HFHS) United States (USA) (US) Université Sorbonne Paris Cité France (FR) University Hospitals Birmingham NHS Foundation Trust United Kingdom (GB) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) University of Utah United States (USA) (US) University of Tokyo Japan (JP) Universitat de Barcelona (UB) / University of Barcelona Spain (ES) Koç-Universität (KU) Turkey (TR) Güven Hospital Turkey (TR) Ospedale Pediatrico Bambino Gesu Italy (IT) Leiden University Medical Center Netherlands (NL) Stanford University United States (USA) (US) Hôpital Necker-Enfants malades France (FR) University of Pittsburgh Medical Center (UPMC) United States (USA) (US) King's College Hospital (KCH) United Kingdom (GB) University of Padua / Universita degli Studi di Padova Italy (IT) Kyushu University / 九州大学 Japan (JP) Birmingham Biomedical Research Centre United Kingdom (GB) University of Texas Southwestern Medical Center (UT Southwestern) United States (USA) (US) Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico Italy (IT)

How to cite

APA:

Montano-Loza, A.J., Ronca, V., Ebadi, M., Hansen, B.E., Hirschfield, G., Elwir, S.,... Oo, Y.H. (2022). Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation. Journal of Hepatology. https://doi.org/10.1016/j.jhep.2022.01.022

MLA:

Montano-Loza, Aldo J., et al. "Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation." Journal of Hepatology (2022).

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