Expanding Liver Transplant Immunosuppression Minimization Via Everolimus

Inclusion Criteria:

1. Subject and/or legal guardian must be able to understand and provide informed consent
2. Adult (age greater than or equal to 18 years of age at time of informed consent) recipient of first liver transplant alone (de novo)
3. Estimated glomerular filtration rate \>=30 ml/min/1.73m\^2 at enrollment using the CKD-EPI 2021 equation
4. Treatment with tacrolimus therapy, with or without mycophenolic acid derivatives and/or corticosteroids
5. Female subjects of childbearing potential with negative pregnancy test upon study entry
6. All subjects of reproductive potential agreeing to use contraception for the duration of the study
7. Previous vaccination or documented immunity to varicella, measles, hepatitis B, pneumococcus, influenza, zoster (if \>=19 years old), and 2019-nCoV (COVID-19) as outlined in the DAIT Vaccination Guideline

Exclusion Criteria:

1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol
2. Active unresolved systemic viral, bacterial, fungal, or parasitic infection requiring oral or intravenous anti-infective therapy
3. History of autoimmune liver disease including autoimmune hepatitis, primary sclerosing cholangitis, and/or primary biliary cirrhosis, or other contraindications to drug withdrawal
4. History of non-hepatic autoimmune disease requiring current or future systemic immunosuppressive therapy other than per study protocol
5. History post-transplant of Hepatic Artery Thrombosis or Portal Vein Thrombosis.
6. History of recurrent cirrhosis after liver transplantation.
7. Chronic use of systemic glucocorticoids, biological immunomodulatory therapy, or other immunosuppressive agents other than per study protocol
8. History of hepatitis B or C virus infection with detectable viral PCR at enrollment
9. History of prior organ transplantation (liver or other type)
10. History of \>= 2 biopsy-proven acute cellular rejection episodes of any severity, \>=1 moderate to severe rejection episode (histologically defined or requiring lymphodepletion therapy), or \>= 1 antibody- mediated rejection episode
11. Active treatment with any mTOR-inhibitor agent (everolimus, sirolimus)
12. Contraindication to treatment with everolimus (open wound or wound infection; urine protein: creatinine ratio \> 0.5 mg/mg; significant pancytopenia (any of the following: WBC \<1.5 K/uL or ANC \<1000 cells/uL or actively being treated with GCSF; Hb \<8.0; platelet count \<50K); serum triglycerides \> 1000 mg/dL; other per PI)
13. Abnormal liver function tests on study entry: Total Bilirubin (TB)\>1.5 mg/dL and Direct Bilirubin (DB) \>1.0 mg/dL, Alkaline Phosphatase (AP) \>200 U/L, and Alanine Aminotransaminase (ALT)\>60 U/L
14. Pregnant on enrollment or plan to become pregnant during the study period
15. Participation in another clinical trial that would interfere with this study's procedures and intervention:

    1. Use of investigational biologic or drug (within 8 weeks of study enrollment)
    2. Additional blood collection that would exceed research blood draw limits
    3. Any other procedure or intervention, in the investigator's opinion would interfere with this study
16. Received live attenuated vaccine(s) within 2 months of enrollment
17. Current, diagnosed, mental illness or current, diagnosed, or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
18. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.