BACKGROUND ITN029, a multicenter pilot trial (n=20) of immunosuppression withdrawal (ISW) in pediatric recipients of parental living donor LTs, identified 12 tolerant participants (pts). The 12 pts have maintained normal liver function off IS for a median of 5.3 (range 4.0-5.8) yrs. Over 5yrs (1yr ISW and 4yrs off IS), we followed allograft inflammation, fibrosis, C4d score and Class II DSA.

METHODS Biopsies obtained prior to (t=0), immediately (t=1y), 2 yrs (t=3y) and 4yrs (t=5y) after ISW were prospectively scored. Inflammation (portal and lobular), fibrosis (portal and central) and C4d (portal vein, portal capillary, sinusoidal, and central vein) were each assigned scores of 0,1,2, and 3 (none, mild, moderate, and severe) and summed. Maximum scores for inflammation, fibrosis and C4d were 6, 6, and 12, respectively. Class II DSA MFIs were summed.

RESULTS The 12 tolerant pts (8 males, 11 White, 11 biliary atresia) were 0.6 (range 0.3-2.4) yrs at LT and 9.0 (range 5.2-12.1) yrs at study entry. Over 5yrs, inflammation increased minimally (3 pts; 1 grade) and fibrosis increased modestly (2 pts, 1 stage; 2 pts, 2 stages) (Fig1). Four pts had class II DSA before ISW; 5 developed DSA during ISW. Neither DSA presence nor strength paralleled inflammation or fibrosis (Fig1). Over 5yrs, C4d scores (available for only 7 pts 2° to freezing artifacts) increased modestly (2.25; range -0.75-4.25) (Fig2).

CONCLUSIONS ISW did not precipitate histological deterioration (increased inflammation or fibrosis) for the majority of tolerant pediatric LT recipients over 5yrs. Class II DSA, occasionally with high MFIs, emerged during and persisted after ISW. C4d score did not track with DSA presence, strength, or change.

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