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Evaluation of Donor Specific Immune Senescence and Exhaustion as Biomarkers of Tolerance Post Liver Transplantation
Bu çalışma, karaciğer nakli (liver transplantation) sonrası bağışıklık baskılayıcı ilaçların kademeli olarak azaltılıp kesilmesini ve donöre özgü immün yaşlanma ile tükenmenin tolerans biyobelirteçleri olarak değerlendirilmesini incelemektedir. Çalışmaya, nakil üzerinden belirli bir süre geçmiş, karaciğer fonksiyonu stabil olan ve kalsinörin inhibitörü temelli tedavi alan nakil hastaları katılabilmektedir. Çalışma Faz 2 aşamasında yürütülmüş ve tamamlanmıştır.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria: Recipient participants must meet all of the following criteria to be eligible for this study: 1. At the time of screening: * 18 to 50 years old and more than 6 years post-transplant OR * Greater than 50 years old and more than 3 years post-transplant 2. Recipient of either deceased or living donor liver transplant. Recipients of living donor transplants must have a donor who is also willing to enroll 3. Recipient of single organ transplant only 4. Must have a screening liver biopsy that fulfills the following criteria based on the central pathology reading: * Portal inflammation and interface activity is preferably absent, but minimal to focal mild portal mononuclear inflammation may be present. Interface necro-inflammatory activity is absent or equivocal/minimal and, if present, involves a minority of portal tracts and not generally associated with fibrosis * Negative for perivenular inflammation * Lymphocytic bile duct damage, ductopenia, and biliary epithelial senescence changes are absent unless there is an alternative, non-immunological explanation (e.g. biliary strictures) * Fibrosis (if present) should be mild overall, and portal-to-portal bridging should not be more than rare. Perivenular and peri-sinusoidal fibrosis should not be more than mild according to the Banff criteria * Findings for obliterative or foam cell arteriopathy are negative 5. Liver function tests (Direct bilirubin, alanine aminotransferase (ALT)), less than twice the upper limit of normal (ULN). ULN values for liver function tests will be defined by ranges from Harrison's Principles of Internal Medicine, 18th edition 6. Receiving calcineurin inhibitor (CNI) based maintenance immunosuppression. Participants may also concurrently receive: * Low dose mycophenolate mofetil (MMF ≤ 1500 mg daily) or mycophenolic acid (≤ 1080 mg daily), OR * Prednisone ≤ 7.5 mg daily, or equivalent corticosteroid 7. Ability to sign informed consent Living donor participants must meet all of the following criteria to be eligible for this study: 1. At the time of screening: ≥18 years old 2. Living donor of the liver allograft of an enrolled recipient participant 3. Ability to sign informed consent 4. Willingness to donate appropriate biologic samples Exclusion Criteria: Recipient participants who meet any of the following criteria will not be eligible for this study: 1. History of hepatitis C virus (HCV) infection (defined as a positive HCV antibody test) 2. Positive antigen-antibody immunoassay for human immunodeficiency virus, HIV-1/2 3. Serum positivity for HBV surface antigen or HBV-DNA 4. History of immune-mediated liver disease in which immunosuppression discontinuation is inadvisable (autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis) 5. Any medical condition associated with a likely need for systemic corticosteroid administration, e.g., reactive airways disease 6. Prospective baseline liver biopsy showing any of the following: (see recipient inclusion criteria #4) * acute rejection according to the Banff global assessment criteria * early or late chronic rejection according to the Banff global assessment criteria * inflammatory activity and/or fibrosis in excess of permissive criteria according to Banff 2012 criteria * any other histological findings that might make participation in the trial unsafe. Eligibility will be determined by the findings on the central biopsy reading 7. Rejection within the 52 weeks prior to screening 8. Estimated glomerular filtration rate (GFR) \<40 ml/min as calculated by CKD-EPI method (to mitigate the risk of worsening renal failure should rejection occur and high level of CNI be required) 9. The need for chronic anti-coagulation that cannot be safely discontinued for a minimum of 1 week to safely perform a liver biopsy 10. Pregnant females and females of childbearing age who are not using an effective method of birth control 11. Current drug or alcohol dependency 12. Inability to comply with the study visit schedule and required assessments, including frequent liver function monitoring and protocol biopsies 13. Inability to comply with study directed treatment 14. Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial 15. Participation in another interventional clinical trial within the 4 weeks prior to screening Living donor participants who meet any of the following criteria will not be eligible for this study: 1\. Any medical condition, such as anemia, coagulopathy, etc., that in the opinion of the principal investigator would interfere with safe participation in the trial