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


DOI: 10.1016/j.jhep.2022.01.022


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.

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Involved external institutions

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

How to cite


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


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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