TY - JOUR
T1 - Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation
AU - International Autoimmune Hepatitis Group (IAIHG)
AU - Montano-Loza, Aldo J.
AU - Ronca, Vincenzo
AU - Ebadi, Maryam
AU - Hansen, Bettina E.
AU - Hirschfield, Gideon
AU - Elwir, Saleh
AU - Alsaed, Mohamad
AU - Milkiewicz, Piotr
AU - Janik, Maciej K.
AU - Marschall, Hanns Ulrich
AU - Burza, Maria Antonella
AU - Efe, Cumali
AU - Calışkan, Ali Rıza
AU - Harputluoglu, Murat
AU - Kabaçam, Gökhan
AU - Terrabuio, Débora
AU - de Quadros Onofrio, Fernanda
AU - Selzner, Nazia
AU - Bonder, Alan
AU - Parés, Albert
AU - Llovet, Laura
AU - Akyıldız, Murat
AU - Arikan, Cigdem
AU - Manns, Michael P.
AU - Taubert, Richard
AU - Weber, Anna Lena
AU - Schiano, Thomas D.
AU - Haydel, Brandy
AU - Czubkowski, Piotr
AU - Socha, Piotr
AU - Ołdak, Natalia
AU - Akamatsu, Nobuhisa
AU - Tanaka, Atsushi
AU - Levy, Cynthia
AU - Martin, Eric F.
AU - Goel, Aparna
AU - Sedki, Mai
AU - Jankowska, Irena
AU - Ikegami, Toru
AU - Rodriguez, Maria
AU - Sterneck, Martina
AU - Weiler-Normann, Christina
AU - Schramm, Christoph
AU - Donato, Maria Francesca
AU - Lohse, Ansgar
AU - Andrade, Raul J.
AU - Patwardhan, Vilas R.
AU - van Hoek, Bart
AU - Biewenga, Maaike
AU - Kremer, Andreas E.
N1 - Publisher Copyright:
© 2022 European Association for the Study of the Liver
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - autoimmune liver disease
KW - graft survival
KW - liver transplantation
KW - recurrent disease
KW - survival
UR - http://www.scopus.com/inward/record.url?scp=85127328871&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2022.01.022
DO - 10.1016/j.jhep.2022.01.022
M3 - Article
C2 - 35143897
AN - SCOPUS:85127328871
SN - 0168-8278
VL - 77
SP - 84
EP - 97
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 1
ER -