Liver and Bile

J Hepatol. 2022;77(1):84–97

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 AE, Ueda Y, Deneau M, Pedersen M, Mayo MJ, Floreani A, Burra P, Secchi MF, Terziroli Beretta-Piccoli B, Sciveres M, Maggiore G, Jafri SM, Debray D, Girard M, Lacaille F, Lytvyak E, Mason AL, Heneghan M, Oo YH; International Autoimmune Hepatitis Group (IAIHG)

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

Background and aims: Autoimmune hepatitis (AIH) can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. The authors 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: They 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 in 31% after 10 years. Age at LT ≤ 42 years (hazard ratio [HR] = 3.15, 95% confidence interval [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 immunoglobulin G 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 autoimmune hepatitis (AIH) following liver transplantation (LT) is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high immunoglobulin G pre-LT. The authors 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.

DOI: 10.1016/j.jhep.2022.01.022