Immune Biomarkers for Predicting Complications After Liver Transplantation

NCT07875595 | Recruiting

• 1 other identifier: HIBAIMMUNOTH
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

This multicenter prospective observational study will evaluate immune biomarkers in adults undergoing liver transplantation. The study aims to describe how immune markers change before and after transplantation and to assess whether these changes are associated with complications such as infections, acute cellular rejection, and viral reactivation during the first year after transplantation. Blood samples will be collected before transplantation, on days 0, 3, and 7 after transplantation, and at months 1, 3, 6, and 12. Biomarkers evaluated will include cytokines, interferons, immunoglobulins, lymphocyte populations, monocyte HLA-DR, neutrophil CD64, functional immune assays, checkpoint molecules, and Torque Teno Virus. Clinical outcomes will be recorded prospectively. Biomarker results will be used for research purposes only and will not modify immunosuppressive treatment or other clinical decisions.

Conditions

Liver Transplantation (LT); Immuno-suppression; Biomarkers / Blood; Rejection; Infections

Keywords

Biomarkers; immunosuppression; Acute Cellular Rejection; Infection; Viral Reactivation; Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• Longitudinal Change in Early Serum Cytokine and Interferon Concentrations

  Change over time in serum concentrations of IL-1β, IL-6, IL-8, IL-12, IL-17A, IL-18, TNF-α, MCP-1, IFN-α2, IFN-γ, IL-10, and TGF-β, comparing liver transplant recipients with immune-mediated versus non-immune-mediated liver disease. Concentrations will be measured in pg/mL. Analyses will be adjusted for the immunosuppressive regimen at each time point, including drug type, dose, and tacrolimus trough concentration.

  Pre-transplant and days 0, 3, and 7 after liver transplantation

Secondary Outcomes (7)

• Longitudinal Change in Immunoglobulin Levels and Leukocyte Profile

  Months 1, 3, 6, and 12 after liver transplantation

• Occurrence of Post-Transplant Infections

  During index hospitalization, 0-3 months, and 3-12 months after liver transplantation

• Diagnostic Performance of HLA-DR and CD64 for Bacterial Infection

  During the first 12 months after liver transplantation

• Occurrence of Acute Cellular Rejection

  Up to 12 months after liver transplantation

• Occurrence of CMV and Other Herpesvirus Reactivation

  Up to 12 months after liver transplantation

Study Arms (2)

Immune-Mediated Liver Disease

Liver transplant recipients with immune-mediated liver disease.

Other: Immune Biomarker Assessment

Non-Immune-Mediated Liver Disease

Liver transplant recipients with non-immune-mediated liver disease.

Other: Immune Biomarker Assessment

Interventions

Immune Biomarker Assessment OTHER

Serial measurement of immune biomarkers in blood samples collected before liver transplantation and on days 0, 3, and 7 and months 1, 3, 6, and 12 after transplantation. Biomarkers include cytokines, interferons, immunoglobulins, lymphocyte populations, monocyte HLA-DR, neutrophil CD64, functional immune assays, checkpoint molecules, and Torque Teno Virus. All measurements are performed for research purposes only and do not modify clinical management or immunosuppressive treatment.

Immune-Mediated Liver Disease; Non-Immune-Mediated Liver Disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult liver transplant recipients treated at Hospital Italiano de Buenos Aires, Hospital Universitario Austral, or Hospital Alemán de Buenos Aires.

You may qualify if:

• Age 18 years or older. Adult patients admitted to the intensive care unit after liver transplantation.

You may not qualify if:

• Refusal to participate in the study. Liver transplantation performed for acute liver failure (fulminant hepatitis).

Sponsors & Collaborators

• Hospital Italiano de Buenos Aires: lead
• Austral University, Argentina: collaborator
• Hospital Aleman: collaborator

Study Sites (3)

Hospital Universitario Austral

Pilar, Buenos Aires, B1629, Argentina

RECRUITING

Hospital Italiano de Buenos Aires

Buenos Aires, Buenos Aires F.D., 1199, Argentina

RECRUITING

Hospital Aleman

Buenos Aires, Buenos Aires F.D., C1118AAT, Argentina

RECRUITING

Related Publications (26)

• Heldman MR, Dunn B, Clemens E, Henderson M, Fisher CE, Rakita RM, Kling CE, Limaye AP. A practical guide to real-world implementation of pre-emptive therapy for Cytomegalovirus disease prevention in high-risk seronegative liver transplant recipients with seropositive donors. Transpl Infect Dis. 2024 Jun;26(3):e14229. doi: 10.1111/tid.14229. Epub 2024 Jan 12.

  PMID: 38214192 BACKGROUND

• Reiss-Gindi N, Hoffman T, Ruderman T, Atamna A, Margalit I, Yahav D. Prophylactic vs preemptive strategy for the prevention of CMV disease in solid organ transplant recipients: systematic review and meta-analysis of randomized controlled trials. Infection. 2025 Jun;53(3):1091-1099. doi: 10.1007/s15010-024-02441-4. Epub 2024 Nov 22.

  PMID: 39576569 BACKGROUND

• Stewart AG, Kotton CN. What's New: Updates on Cytomegalovirus in Solid Organ Transplantation. Transplantation. 2024 Apr 1;108(4):884-897. doi: 10.1097/TP.0000000000004855. Epub 2023 Oct 30.

  PMID: 37899366 BACKGROUND

• Lizaola-Mayo BC, Rodriguez EA. Cytomegalovirus infection after liver transplantation. World J Transplant. 2020 Jul 29;10(7):183-190. doi: 10.5500/wjt.v10.i7.183.

  PMID: 32844094 BACKGROUND

• Fontela PS, O'Donnell S, Papenburg J. Can biomarkers improve the rational use of antibiotics? Curr Opin Infect Dis. 2018 Aug;31(4):347-352. doi: 10.1097/QCO.0000000000000467.

  PMID: 29794541 BACKGROUND

• Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Nguyen MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young JA, Bennett JE. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60. doi: 10.1093/cid/ciw326. Epub 2016 Jun 29.

  PMID: 27365388 BACKGROUND

• Salmanton-Garcia J, Giacinta A, Giannella M, Vena A, Munoz P, Cornely OA, Valerio M. Current trends on antifungal prophylaxis in solid organ transplantation: a study from ESCMID-EFISG, ESCMID-ESGICH, SITA, and SEIMC-GESITRA-IC. Infection. 2025 Dec;53(6):2411-2420. doi: 10.1007/s15010-025-02575-z. Epub 2025 Jul 4.

  PMID: 40614031 BACKGROUND

• Denzel C, Riese J, Hohenberger W, Born G, Kockerling F, Tschaikowsky K, Reith HB, Reck T, Haupt W. Monitoring of immunotherapy by measuring monocyte HLA-DR expression and stimulated TNFalpha production during sepsis after liver transplantation. Intensive Care Med. 1998 Dec;24(12):1343-4. doi: 10.1007/s001340050775. No abstract available.

  PMID: 9885893 BACKGROUND

• Peng B, Yang M, Zhuang Q, Li J, Zhang P, Liu H, Cheng K, Ming Y. Standardization of neutrophil CD64 and monocyte HLA-DR measurement and its application in immune monitoring in kidney transplantation. Front Immunol. 2022 Nov 23;13:1063957. doi: 10.3389/fimmu.2022.1063957. eCollection 2022.

  PMID: 36505404 BACKGROUND

• Haveman JW, van den Berg AP, van den Berk JM, Mesander G, Slooff MJ, de Leij LH, The TH. Low HLA-DR expression on peripheral blood monocytes predicts bacterial sepsis after liver transplantation: relation with prednisolone intake. Transpl Infect Dis. 1999 Sep;1(3):146-52. doi: 10.1034/j.1399-3062.1999.010302.x.

  PMID: 11428984 BACKGROUND

• Regele F, Haupenthal F, Doberer K, Gorzer I, Kapps S, Strassl R, Bond G. The kinetics of Torque Teno virus plasma load following calcineurin inhibitor dose change in kidney transplant recipients. J Med Virol. 2024 Mar;96(3):e29554. doi: 10.1002/jmv.29554.

  PMID: 38511586 BACKGROUND

• Engel B, Gorzer I, Campos-Murguia A, Hartleben B, Puchhammer-Stockl E, Jaeckel E, Taubert R. Association of torque teno virus viremia with liver fibrosis in the first year after liver transplantation. Front Immunol. 2023 Jul 18;14:1215868. doi: 10.3389/fimmu.2023.1215868. eCollection 2023.

  PMID: 37533865 BACKGROUND

• Ruiz P, Martinez-Picola M, Santana M, Munoz J, Perez-Del-Pulgar S, Koutsoudakis G, Sastre L, Colmenero J, Crespo G, Navasa M. Torque Teno Virus Is Associated With the State of Immune Suppression Early After Liver Transplantation. Liver Transpl. 2019 Feb;25(2):302-310. doi: 10.1002/lt.25374.

  PMID: 30375165 BACKGROUND

• Mian M, Natori Y, Ferreira V, Selzner N, Husain S, Singer L, Kim SJ, Humar A, Kumar D. Evaluation of a Novel Global Immunity Assay to Predict Infection in Organ Transplant Recipients. Clin Infect Dis. 2018 Apr 17;66(9):1392-1397. doi: 10.1093/cid/cix1008.

  PMID: 29281051 BACKGROUND

• Sood S, Haifer C, Yu L, Pavlovic J, Churilov L, Gow PJ, Jones RM, Angus PW, Visvanathan K, Testro AG. A novel immune function biomarker identifies patients at risk of clinical events early following liver transplantation. Liver Transpl. 2017 Apr;23(4):487-497. doi: 10.1002/lt.24730.

  PMID: 28133934 BACKGROUND

• Dendle C, Mulley WR, Holdsworth S. Can immune biomarkers predict infections in solid organ transplant recipients? A review of current evidence. Transplant Rev (Orlando). 2019 Apr;33(2):87-98. doi: 10.1016/j.trre.2018.10.001. Epub 2018 Oct 9.

  PMID: 30551846 BACKGROUND

• Iovino L, Taddei R, Bindi ML, Morganti R, Ghinolfi D, Petrini M, Biancofiore G. Clinical use of an immune monitoring panel in liver transplant recipients: A prospective, observational study. Transpl Immunol. 2019 Feb;52:45-52. doi: 10.1016/j.trim.2018.11.001. Epub 2018 Nov 7.

  PMID: 30414446 BACKGROUND

• Boix F, Alfaro R, Jimenez-Coll V, Mrowiec A, Martinez-Banaclocha H, Botella C, Moya-Quiles MR, Sanchez-Bueno F, Robles R, de la Pena-Moral J, Ramirez P, Pons JA, Llorente S, Minguela A, Muro M. A high concentration of TGF-beta correlates with opportunistic infection in liver and kidney transplantation. Hum Immunol. 2021 Jun;82(6):414-421. doi: 10.1016/j.humimm.2021.03.007. Epub 2021 Apr 2.

  PMID: 33814194 BACKGROUND

• Dogan N, Husing-Kabar A, Schmidt HH, Cicinnati VR, Beckebaum S, Kabar I. Acute allograft rejection in liver transplant recipients: Incidence, risk factors, treatment success, and impact on graft failure. J Int Med Res. 2018 Sep;46(9):3979-3990. doi: 10.1177/0300060518785543. Epub 2018 Jul 12.

  PMID: 29996675 BACKGROUND

• Roberts MB, Fishman JA. Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression". Clin Infect Dis. 2021 Oct 5;73(7):e1302-e1317. doi: 10.1093/cid/ciaa1189.

  PMID: 32803228 BACKGROUND

• Khedr L, Teama N, El Sharkawy M. Infections in the first year of living related kidney transplantation in a young transplant cohort. BMC Nephrol. 2023 Nov 7;24(1):328. doi: 10.1186/s12882-023-03379-9.

  PMID: 37936062 BACKGROUND

• Louis K, Tabib T, Macedo C, Wang J, Cantalupo P, Chandran U, Gu X, Lucas M, Randhawa P, Abundis M, Das J, Singh H, Lefaucheur C, Metes D. High-dimensional profiling of immune responses to kidney transplant reveals heterogeneous T helper 1 and B cell effectors associated with rejection. Am J Transplant. 2025 Apr;25(4):706-719. doi: 10.1016/j.ajt.2024.10.009. Epub 2024 Oct 16.

  PMID: 39419342 BACKGROUND

• Kwong AJ, Kim WR, Lake JR, Schladt DP, Handarova D, Howell J, Schumacher B, Weiss S, Snyder JJ, Israni AK. OPTN/SRTR 2023 Annual Data Report: Liver. Am J Transplant. 2025 Feb;25(2S1):S193-S287. doi: 10.1016/j.ajt.2025.01.022.

  PMID: 39947804 BACKGROUND

• Agostini C, Buccianti S, Risaliti M, Fortuna L, Tirloni L, Tucci R, Bartolini I, Grazi GL. Complications in Post-Liver Transplant Patients. J Clin Med. 2023 Sep 24;12(19):6173. doi: 10.3390/jcm12196173.

  PMID: 37834818 BACKGROUND

• Marciano S, Martinez Morales JC, Juana C, de Santibanes M, Pekolj J, de Santibanes E, Francisconi M, Uno Tala JW, Burgos Pratx LD, Gadano A, Ardiles V. The building of an institutional liver transplant registry: opportunities and challenges. J Int Med Res. 2024 Jul;52(7):3000605241264232. doi: 10.1177/03000605241264232.

  PMID: 39079129 BACKGROUND

• Haddad L, Marciano S, Cleres M, Zerega A, Pinero F, Orozco F, Braslavsky G, Mendizabal M, Gondolesi G, Gil O, Silva M, Mastai R, Imventarza O, Descalzi V, Gadano A. Characteristics of Liver Transplantation in Argentina: A Multicenter Study. Transplant Proc. 2018 Mar;50(2):478-484. doi: 10.1016/j.transproceed.2017.11.072.

  PMID: 29579832 BACKGROUND

MeSH Terms

Conditions

Rejection, Psychology; Infections

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Central Study Contacts

Jorge Martinez, MD

CONTACT

+541149590200; jorgec.martinez@hospitalitaliano.org.ar

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 8, 2026
• First Posted: October 15, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: October 15, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

AR (3)