*Purpose: Recent surveillance biopsy studies strongly associate high normal ALT (>35U/L) with inflammatory histopathology and low normal ALT (<15U/L) with its absence, suggesting that ALT can inform decision-making regarding immunosuppression (IS) dosing and/or biopsy^1,2. We aim to map liver transplant (LT) recipients by a single ALT metric for the 1-year period starting 4 years after LT to show the distribution of ALT for a pediatric population.

*Methods: Data on 97 children transplanted 2005-2016 with ≥1 ALT during the 5^th year after LT were extracted and analyzed. We first calculated the median ALT/AST for each month of the year. The medians were then used to calculate the mean ALT/AST for the year. Univariable analysis identified associations between mean ALT and multiple clinical variables including tacrolimus standard deviation (SD), which was calculated when ≥3 tacrolimus levels were available.

*Results: For our cohort of 97 children [49 male; 77 deceased donors; median (IQR) age at LT of 2.47 (10.9) yrs], the 25^th, 50^th, and 75^th %iles for mean 4-5yr ALT/AST (U/L) were 19/26, 28/36, 47/49, respectively (Fig 1A). ALT correlated strongly with AST (R=0.85). Variables associated with high mean 4-5yr ALT include age at LT >15yrs (n=13; p=0.0006), chronic rejection (CR) diagnosis prior to yr4 (n=4; p=0.03), and acute cellular rejection (ACR) episode in yr4-5 (n=5; p=0.0001). Sex, donor type, LT indication, retransplant within 30 days, and ACR history were not correlated. Compared to children with ALT<28 (1^st, 2^nd quartiles combined), those with ALT 28-47 (3^rd) or >47 (4^th) had significantly higher tacrolimus SDs [1.04 vs. 1.72 (3^rd) and 2.02 (4^th)] and higher % with tacrolimus SD≥2 [10% vs. 29% (3^rd) and 52% (4^th)] (Figure 1B). Mean tacrolimus levels did not significantly differ between the ALT quartiles.

*Conclusions: Among children with LTs, 50% have low mean 4-5yr ALT and low tacrolimus SD, and thus perhaps are prime candidates for IS minimization. For the remaining 50% with moderate or high mean 4-5yr ALT, additional metrics such as tacrolimus SD and/or donor specific antibody^1,2 may further risk stratify to motivate implementation of adherence measures, liver biopsy and/or IS escalation. Nuanced consideration of readily available, non-invasive data may facilitate safe and personalized IS dosing and reduce the frequency of allograft biopsy. (¹Vionnet, JHep 2021; ²Feng, Gastro 2018)

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