A systematic review of post-liver transplantation treatment and outcomes for late T-cell mediated, chronic ductopenic, and antibody-mediated rejection

BACKGROUND: Compared to the treatment for acute T-cell-mediated rejection, management of late T-cell-mediated rejection, chronic ductopenic rejection, and antibody-mediated rejection is more heterogeneous. METHODS: We conducted a systematic review of studies on the treatment of liver transplant recipients with late T-cell-mediated rejection, chronic ductopenic rejection, and antibody-mediated rejection from 2001 to 2024. Studies were included if they reported the Banff criteria for diagnosing rejection, treatment regimen(s), and response rates. RESULTS: Twenty studies that included a combined 374 rejection episodes were identified. Among the 20 studies, the total number of liver transplant recipients with late T-cell-mediated rejection, chronic ductopenic rejection, ABO-compatible antibody-mediated rejection, and chronic antibody-mediated rejection were 226, 67, 43, and 38, respectively. The most common regimens and response rates for late T-cell-mediated rejection, chronic ductopenic rejection, acute antibody- mediated rejection, and chronic antibody-mediated rejection were high-dose steroids and adjusting baseline immunosuppression (55%-100%), adjusting baseline immunosuppression with or without an mTOR inhibitor (25%-52%), high-dose steroids, plasma exchange or plasmapheresis and rituximab (50%-80%), and rituximab containing regimens (52%-63%), respectively. The study regimens were heterogeneous, and 7 (35%) studies were more than 10 years old. CONCLUSIONS: Higher-quality and contemporaneous data are needed to apply uniform definitions for treatment response rates and standardized treatment regimens. Regimens warranting further study include increasing baseline immunosuppression for late T-cell-mediated rejection and mTOR inhibitors for treating chronic ductopenic rejection.