Background: Long term allograft health after rejection during ISW has not been previously assessed. We compare baseline and 4yr graft histology of 20 rejectors in iWITH, an ISW trial (NCT01638559).

Methods: ISW occurred over 36-48wks with liver test monitoring every 2wks. All subjects had Yr0 and Yr4 biopsies. For-cause biopsy was triggered by clinical judgment and mandated for ALT or GGT>100 IU/L. Rejection treatment was by site standard of care; resolution was defined as ALT and GGT<1.5X at study entry. A central pathologist graded rejection by Banff criteria and quantified fibrosis by Ishak stage (F0-F6) and Liver Allograft Fibrosis Score (LAFSc;F0-F9,Venturi AJT 2012).

Results: 88 subjects initiated ISW. Of the 35 with rejection, 20 have completed the study.(Table) Rejection occurred at a median(IQR) 25(20-31)wks after starting ISW. 18 were by biopsy (mild/moderate 13/5); 2 were diagnosed clinically. 19 resolved rejection in median(IQR) 11(7-17)wks. At the end of study, all 20 were on TAC monotherapy; 15 were on TAC≤study entry dose. Compared to Yr0 biopsy, 15/20 Yr4 biopsies were stable or improved by Ishak and LAFSc.(Figure) 4/20 had Ishak [Delta]+1 and LAFSc [Delta]+1 (3 portal;1 perivenular). A single subject had Ishak [Delta]+2 (F0→2) and LAFSc [Delta]+3 (F0→F3;[Delta]+1 portal, sinusoidal and perivenular).

Conclusion: Rejection during protocolized ISW was rapidly diagnosed, histologically mild/moderate and readily reversed. 95% of rejectors showed stable graft histology over 4yrs. Intense lab test monitoring and low biopsy threshold may be essential to ensure safe IS minimization or withdrawal.

CITATION INFORMATION: Venkat V., Bucuvalas J., Martinez M., Spain K., Mazariegos G., Demetris A., Feng S. Long Term Histologic Allograft Health is Preserved Despite Rejection during Protocolized Immunosuppression Withdrawal (ISW) in Stable Pediatric Liver Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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