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

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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