Recurrence of autoimmune hepatitis cholestatic variant syndromes after liver transplantation affects graft and patient survival

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dc.contributor.authorRonca, Vincenzo
dc.contributor.authorParente, Alessandro
dc.contributor.authorLytvyak, Ellina
dc.contributor.authorHansen, Bettina E.
dc.contributor.authorHirschfield, Gideon
dc.contributor.authorBonder, Alan
dc.contributor.authorEbadi, Maryam
dc.date.accessioned2026-04-04T13:35:00Z
dc.date.available2026-04-04T13:35:00Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractBackground & Aims: A significant proportion of patients with variant syndromes (VSs), namely autoimmune hepatitis/primary biliary cholangitis or autoimmune hepatitis/primary sclerosing cholangitis, require liver transplantation (LT) despite treatment. The frequency of disease recurrence and the effect on graft survival are yet to be clarified. The aim of this international, multicentric, retrospective study is to evaluate the risk factors associated with recurrence and the impact of the disease recurrence after LT on graft and patient survival. Methods: We evaluated 166 patients undergoing LT for VS in 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 with a higher risk of recurrence of autoimmune disease based on a histological and radiological diagnosis. Cumulative probabilities of graft and overall survival after LT were calculated using a semi-Markov model. Results: The autoimmune pattern of recurrence resembled the original VS in 19 cases (61%). Recurrence of autoimmune liver disease (rALD) after LT was observed in 23% and 33% of patients after 5 and 10 years, respectively. Increased alkaline phosphatase (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.13-2.25, p <0.01) and alanine aminotransferase (HR 1.25, 95% CI 1.01-1.53, p = 0.03) at 12 months after LT and acute rejection (HR 3.58, 95% CI 1.60-7.73, p <0.01) were associated with a higher risk of VS recurrence, whereas the use of predniso(lo)ne was associated with a reduced risk (HR 0.30, 95% CI 0.14-0.64, p <0.01). After adjusting for alanine aminotransferase and alkaline phosphatase at 12 months, the use of predniso(lo)ne was found to be independently and negatively associated with recurrent disease. The rALD was found to be significantly associated with graft loss and patient survival in the multivariate Cox regression analysis with a time-dependent covariate. The 5-and 10-year probabilities of graft survival were 68% and 41% in patients with recurrent VS compared with 83% and 60% in patients without recurrent disease, respectively (p = 0.01). The overall survival was significantly reduced in patients with recurrent disease (p = 0.01), with event probability at 5 and 10 years of 75% and 49% vs. 84% and 60% in patients without recurrence, respectively. Conclusions: rALD after LT is frequent and is associated with elevation in liver enzymes within the first year after LT and rejection episodes. According to our data, VS recurrence appears to be associated with poorer graft and patient survival. Further studies are needed to explore strategies that can prevent VS recurrence or mitigate its potential impact. (c) 2025 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.description.sponsorshipUniversity of Alberta Hospital Foundation (UHF); Canadian Liver Foundation (CLF)
dc.description.sponsorshipVR received funding from the EASL Juan Rodes PhD fellowship programme. ME received funding from the Canadian Institutes of Health Research (CIHR) - Institute of Nutrition, Metabolism, and Diabetes (INMD) Fellowship-Hepatology, in partnership with the Canadian Association for the Study of the Liver (CASL) and the Canadian Liver Foundation (CLF) . YHO received funding from the Sir Jules Thorn Biomedical Research Award, Medical Research Foundation, MRC, and Queen Elizabeth Hospital Birmingham Charity. AJM-L received funding from the University of Alberta Hospital Foundation (UHF) and the Canadian Liver Foundation (CLF) .
dc.identifier.doi10.1016/j.jhepr.2025.101332
dc.identifier.issn2589-5559
dc.identifier.issue5
dc.identifier.orcid0000-0001-5651-9010
dc.identifier.orcid0000-0003-1603-5147
dc.identifier.orcid0000-0002-6736-2255
dc.identifier.orcid0000-0003-0761-1333
dc.identifier.orcid0000-0002-0345-963X
dc.identifier.orcid0000-0002-7520-744X
dc.identifier.orcid0000-0002-8791-191X
dc.identifier.pmid40276483
dc.identifier.scopus2-s2.0-105002312763
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.jhepr.2025.101332
dc.identifier.urihttps://hdl.handle.net/11616/109537
dc.identifier.volume7
dc.identifier.wosWOS:001472702700001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJhep Reports
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectAutoimmunity
dc.subjectRecurrence
dc.subjectLiver transplantation
dc.titleRecurrence of autoimmune hepatitis cholestatic variant syndromes after liver transplantation affects graft and patient survival
dc.typeArticle

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