Number of participants that are operationally tolerant, defined as those who successfully withdraw from immunosuppression and maintain normal allograft status as assessed by liver biopsy and liver tests 12 months after complete immunosuppression withdrawal.

Intent-to-Treat

This composite endpoint is comprised of clinical complications related to immunosuppression withdrawal and is defined as the occurrence of any of the following: death or graft loss, histologic evidence of refractory acute rejection or biopsy confirmed chronic rejection (CR).

Intent-to-Treat

The median time (in days) from start of withdrawal from immunosuppression drugs to increasing or re-starting immunosuppression.

Participants that either restarted immunosuppression or increased their dose of immunosuppression

The median time (in weeks) from biopsy proven rejection to resolution of rejection defined as both liver function tests Alanine Aminotransferase (ALT) and Gamma-Glutamyl Transferase (GGT) returning to ≤ 1.5 the baseline values.

Intent-to-Treat

Number of biopsies that were diagnosed as histologic acute rejection in participants who initiated immunosuppression withdrawal by severity of rejection episode. Rejection severity (mild, moderate, severe) is based on the Banff global assessment grade according to the central pathology reading of the liver biopsy. Mild severity criteria: rejection infiltrate in a minority of triads that is generally mild and confined within the portal spaces. Moderate rejection criteria: rejection infiltrate expanding most or all of the triads. Severe rejection criteria: rejection infiltrate expanding most or all of the triads with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis.

BPAR: biopsy-proven acute rejection.

Intent-to-Treat

The clinical severity of acute rejection was descriptively analyzed using hierarchical categories, as follows:

• Dose increase: Increase in IS dose and/or frequency but to a level less than the regimen at study entry, prior to initiating ISW
• Reinstitution: Returning to the regimen at study entry, prior to ISW
• Intensification: Increased IS dose compared with the dose at study entry, prior to ISW
• Conversion: Change to different IS drug
• Addition: Initiation of a second IS drug;
• Corticosteroids: Administration of any intravenous or oral corticosteroids
• Antibody (Ab) treatment: Administration of any rabbit thymoglobulin; usually with corticosteroids

Participants who experienced rejection (biopsy-proven or clinical)

Reasons participants discontinued immunosuppression withdrawal, such as Biopsy Proven Acute Rejection, Chronic Rejection, Clinical Rejection, Death, Pregnancy, etc.). Only the root cause for discontinuation for each subject is presented in these results if multiple events led to discontinuation of immunosuppression withdrawal.

Participants who failed immunosuppression withdrawal.

The impact of ISW on allograft fibrosis using the Ishak scoring system to measure the change in fibrosis from the screening liver biopsy to the end-of-study (month-48) liver biopsy.

In the Ishak histologic scoring system, the higher the score/stage, the more fibrosis: Scores range from 0 to 6, with 6 representing the most fibrosis: 0=No fibrosis; 1=Fibrous expansion of some portal areas, with or without short fibrous septa; 2=Fibrous expansion of most portal areas, with or without short fibrous septa; 3=Fibrous expansion of most portal areas, with occasional portal to portal bridging; 4=Fibrous expansion of portal areas with marked bridging (portal to portal) as well as portal to central; 5=Marked bridging (portal to portal and/or portal to central) with occasional nodules (incomplete cirrhosis); and 6=Cirrhosis, probable or definite.

Decrease in score from screening (baseline) indicates improvement

Intent-to-Treat

-Of the original 88 participants, 3 participants did not finish the study and 1 participant did not complete the final liver biopsy.

Median participant duration of operational tolerance. Duration of operational tolerance is defined as the number of days that participants are not taking immunosuppression medications.

Participants that Completed Withdrawal and were Operationally Tolerant

The mean percent of immunosuppression (IS) dose reduction from baseline to the time of immunosuppression withdrawal failure. Immunosuppression withdrawal failure is defined as any incidence of increasing immunosuppression medications instead of completing withdrawal.

Intent-to-Treat who failed immunosuppression withdrawal

Change of immunosuppression (IS) dose from baseline to end of study for all participants not deemed tolerant by the trial definition either due to discontinuing IS withdrawal or completing withdrawal but not meeting the criteria for tolerance on the primary endpoint biopsy assessment.

Intent-to-Treat participants who were not operationally tolerant and who remained on the same medication throughout the study. Three subjects that were not operationally tolerant converted to alternate immunosuppression medications.

Health related quality of life was measured by the PedsQL 4.0 Generic Core scale, the Multidimensional Fatigue scale, and the PedsQL 3.0 Transplant module. Change was calculated as the difference between the questionnaire completed at the initiation of withdrawal and at month 36 for the total generic score, the total fatigue score, and total transplant score. This change was calculated separately for tolerant and non-tolerant subjects. Each score ranges from 0-100, with a higher score indicating a better quality of life.

Intent-to-Treat