*Purpose: There is limited evidence on the optimal maintenance immunosuppression after liver transplant (LT) for primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH). This study evaluated the impact of dual (calcineurin inhibitor, CNI, plus antimetabolite) versus single-agent immunosuppression (CNI alone) on acute cellular rejection (ACR) in LT recipients with autoimmune liver diseases.

*Methods: We conducted a single-center, retrospective review of adult LT recipients for PBC, PSC, or AIH from May 1991 to Jan 2019. Patients with repeat LT or post-LT sirolimus or everolimus use were excluded. The primary outcome, ACR, was defined as biopsy-proven ACR or treatment for biochemically-suspected ACR. Primary disease recurrence was a secondary outcome. Immunosuppression regimen changes and time on each regimen until ACR or end of ACR-free surveillance were recorded. Data were analyzed using summary statistics and multivariable Cox proportional hazards regression with regimens as a time-dependent covariate.

*Results: The cohort included 182 LT recipients (64 PBC, 67 PSC, 51 AIH) [Table 1]. Cold ischemic time and CMV risk were similar in the 3 groups (p≥0.410). Most (81.2%) received methylprednisolone induction, which did not differ by diagnosis (p=0.583). After adjusting for type of autoimmune liver disease (p=0.064), CMV risk (p=0.18), and the significantly-reduced risk associated with age (p=0.004), in comparison to triple-agent regimens with steroids, ACR risk associated with dual (HR=0.51; 95% CI 0.27-0.96, p=0.038) and single-agent (HR=0.08; 95% CI, 0.02-0.34, p=0.001) immunosuppression was statistically comparable, as reflected by the overlapping hazard ratios. Over the surveillance period, percentages of patients with recurrence for PBC, PSC, and AIH were 18.8%, 19.4%, and 21.6% and averaged at 58±37, 74±52, and 50±40 months post-transplant, respectively.

*Conclusions: In this cohort of liver transplant recipients for PBC, PSC, or AIH, a comparable risk of ACR was observed in those taking CNI plus antimetabolite versus CNI monotherapy. AIH did not confer an increased risk of ACR versus PBC and PSC. Immunosuppression minimization may be considered in this patient population. Further studies are needed to evaluate patient-specific ACR risk factors that may affect the feasibility of this approach.

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