Risk factors and outcomes associated with recurrent autoimmune hepatitis

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. (C) 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

C1 [Montano-Loza, Aldo J.; Ebadi, Maryam; Lytvyak, Ellina; Mason, Andrew L.] Univ Alberta, Div Gastroenterol, Edmonton, AB, Canada.

[Montano-Loza, Aldo J.; Ebadi, Maryam; Lytvyak, Ellina; Mason, Andrew L.] Univ Alberta, Liver Unit, Edmonton, AB, Canada.

[Ronca, Vincenzo] Univ Birmingham, Ctr Liver Res, Birmingham, W Midlands, England.

[Ronca, Vincenzo] Univ Birmingham, NIHR Birmingham BRC, Birmingham, W Midlands, England.

[Ronca, Vincenzo] Univ Birmingham, Univ Hosp Birmingham NHS Fdn Trust, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England.

[Hansen, Bettina E.; Hirschfield, Gideon; Onofrio, Fernanda de Quadros; Selzner, Nazia] Univ Toronto, Univ Hlth Network, Toronto Ctr Liver Dis, Toronto, ON, Canada.

[Elwir, Saleh; Alsaed, Mohamad] Baylor Univ, Med Ctr, Dallas, TX USA.

[Milkiewicz, Piotr; Janik, Maciej K.] Med Univ Warsaw, Liver & Internal Med Unit, Warsaw, Poland.

[Marschall, Hanns-Ulrich; Burza, Maria Antonella] Sahlgrens Univ Hosp, Gothenburg, Sweden.

[Efe, Cumali] Harran Univ Hosp, Dept Gastroenterol, Sanliurfa, Turkey.

[Caliskan, Ali Riza; Harputluoglu, Murat] Inonu Univ, Dept Gastroenterol, Sch Med, Malatya, Turkey.

[Kabacam, Gokhan] Guven Hosp Ankara, Clin Gastroenterol & Liver Transplantat, Ankara, Turkey.

[Terrabuio, Debora] Univ Sao Paulo, Sch Med, Dept Gastroenterol, Sao Paulo, Brazil.

[Bonder, Alan; Patwardhan, Vilas R.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.

[Pares, Albert; Llovet, Laura] Univ Barcelona, Hosp Clin, Liver Unit, CIBERehd,IDIBAPS, Barcelona, Spain.

[Akyildiz, Murat] Koc Univ, Dept Gastroenterol, Sch Med, Istanbul, Turkey.

[Akyildiz, Murat] Koc Univ, Sch Med, Liver Transplantat Ctr, Istanbul, Turkey.

[Arikan, Cigdem] Koc Univ, Sch Med Pediat Gastroenterol & Hepatol, Organ Transplantat Ctr, Koc Univ Res Ctr Translat Med KUTTAM, Istanbul, Turkey.

[Manns, Michael P.; Taubert, Richard; Weber, Anna-Lena] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, European Reference Network Hepatol Dis ERN RARE L, Hannover, Germany.

[Schiano, Thomas D.; Haydel, Brandy] Mt Sinai Med Ctr, Div Liver Dis, Recanati Miller Transplantat Inst, New York, NY 10029 USA.

[Czubkowski, Piotr; Socha, Piotr; Oldak, Natalia] Childrens Mem Hlth Inst, Dept Gastroenterol Hepatol Nutr Disorders & Pedia, Warsaw, Poland.

[Akamatsu, Nobuhisa] Univ Tokyo, Tokyo, Japan.

[Tanaka, Atsushi] Teikyo Univ, Sch Med, Dept Med, Tokyo, Japan.

[Levy, Cynthia; Martin, Eric F.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.

[Goel, Aparna; Sedki, Mai] Stanford Univ, Stanford, CA 94305 USA.

[Jankowska, Irena] Childrens Mem Hlth Inst, Warsaw, Poland.

[Ikegami, Toru] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Sci, Fukuoka, Japan.

[Rodriguez, Maria; Sterneck, Martina; Weiler-Normann, Christina; Schramm, Christoph] UKE Hamburg, Hamburg, Germany.

[Donato, Maria Francesca] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Liver Tranplant Hepatol Unit, Div Gastroenterol & Hepatol, Milan, Italy.

[Lohse, Ansgar] Univ Med Ctr, Hamburg, Germany.

[Andrade, Raul J.] Univ Malaga, Univ Hosp, Gastroenterol Serv IBIMA, Malaga, Spain.

[Andrade, Raul J.] Univ Malaga, CIBERehd, Malaga, Spain.

[van Hoek, Bart; Biewenga, Maaike] Leiden Univ Med Ctr, Leiden, Netherlands.

[Kremer, Andreas E.] Univ Hosp Erlangen, Dept Med, Erlangen, Germany.

[Kremer, Andreas E.] Friedrich Alexander Univ Erlangen Nurnberg, Erlangen, Germany.

[Kremer, Andreas E.] Univ Zurich, Univ Hosp Zurich, Dept Gastroenterol & Hepatol, Zurich, Switzerland.

[Ueda, Yoshihide] Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto, Japan.

[Deneau, Mark] Univ Utah, Salt Lake City, UT USA.

[Pedersen, Mark; Mayo, Marlyn J.] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA.

[Floreani, Annarosa; Burra, Patrizia] Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy.

[Secchi, Maria Francesca] Univ Padua, Padua, Italy.

[Beretta-Piccoli, Benedetta Terziroli] Epatoctr Ticino, Lugano, Switzerland.

[Beretta-Piccoli, Benedetta Terziroli] Univ Svizzera Italiana, Lugano, Switzerland.

[Sciveres, Marco] UPMC Pediat Liver Ctr, Palermo, Italy.

[Maggiore, Giuseppe] IRCCS Bambino Gesu Pediat Hosp, Hepatogastroenterol Nutr & Liver Transplant, Rome, Italy.

[Jafri, Syed-Mohammed] Henry Ford Hlth Syst, Detroit, MI USA.

[Debray, Dominique; Girard, Muriel] Univ Paris, Hop Necker, Pediat Liver Unit, French Natl Reference Ctr Rare Dis BA & Genet Cho, Paris, France.

[Lacaille, Florence] Hop Necker Enfants Malad, Gastroenterol Hepatol Nutr Unit, Paris, France.

[Heneghan, Michael] Kings Coll Hosp NHS Fdn Trust, London, England.

[Oo, Ye Htun] Univ Birmingham, Ctr Liver & Gastro Res, Birmingham, W Midlands, England.

[Oo, Ye Htun] Univ Birmingham, Natl Inst Hlth Res, Birmingham Biomed Res Ctr, Birmingham, W Midlands, England.

[Oo, Ye Htun] Univ Hosp Birmingham NHS Fdn Trust, Liver Transplant & Hepatobiliary Unit, ERN Rare Liver Ctr, Birmingham, W Midlands, England.