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

• Published in: Journal of hepatology Vol. 77; no. 1; pp. 84 - 97
• Main Authors: Montano-Loza, Aldo J., Ronca, Vincenzo, Ebadi, Maryam, Hansen, Bettina E., Hirschfield, Gideon, Elwir, Saleh, Alsaed, Mohamad, Milkiewicz, Piotr, Janik, Maciej K., Marschall, Hanns-Ulrich, Burza, Maria Antonella, Efe, Cumali, Calışkan, Ali Rıza, Harputluoglu, Murat, Kabaçam, Gökhan, Terrabuio, Débora, de Quadros Onofrio, Fernanda, Selzner, Nazia, Bonder, Alan, Parés, Albert, Llovet, Laura, Akyıldız, Murat, Arikan, Cigdem, Manns, Michael P., Taubert, Richard, Weber, Anna-Lena, Schiano, Thomas D., Haydel, Brandy, Czubkowski, Piotr, Socha, Piotr, Ołdak, Natalia, Akamatsu, Nobuhisa, Tanaka, Atsushi, Levy, Cynthia, Martin, Eric F., Goel, Aparna, Sedki, Mai, Jankowska, Irena, Ikegami, Toru, Rodriguez, Maria, Sterneck, Martina, Weiler-Normann, Christina, Schramm, Christoph, Donato, Maria Francesca, Lohse, Ansgar, Andrade, Raul J., Patwardhan, Vilas R., van Hoek, Bart, Biewenga, Maaike, Kremer, Andreas E., Ueda, Yoshihide, Deneau, Mark, Pedersen, Mark, Mayo, Marlyn J., Floreani, Annarosa, Burra, Patrizia, Secchi, Maria Francesca, Beretta-Piccoli, Benedetta Terziroli, Sciveres, Marco, Maggiore, Giuseppe, Jafri, Syed-Mohammed, Debray, Dominique, Girard, Muriel, Lacaille, Florence, Lytvyak, Ellina, Mason, Andrew L., Heneghan, Michael, Oo, Ye Htun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2022; Elsevier Science Ltd
• Subjects: Age; autoimmune liver disease; graft survival; Hepatitis; Immunoglobulin G; Immunosuppression; Liver; Liver transplantation; Mycophenolate mofetil; Mycophenolic acid; Patients; recurrent disease; Risk factors; Survival; Transplants & implants; graft survival; autoimmune liver disease; recurrent disease; liver transplantation; survival
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2022.01.022

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.
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•Recurrent AIH frequently occurs following LT.•Recurrent AIH is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and higher IgG pre-LT.•Recurrent AIH impacts on graft and overall survival after LT.•Recurrent AIH following LT is clinically meaningful and requires improved management strategies.