Inflammatory and Anti-Inflammatory Gene Expressions in Liver Transplant Patients

Investigation of Inflammatory and Anti-Inflammatory Gene Expressions in Liver Transplant Patients Before and After the Operation

In our study, some inflammatory Interleukin-2 , Interleukin-6, Interferon-γ, Tumor Necrosis Factor-α and anti-inflammatory Interleukin-4 and Interleukin-10 cytokine genes expressions and Triggering Receptor Expressed On Myeloid Cells- 1, which contributes to the pathology of acute and chronic inflammatory diseases; Human Leukocyte Antigen-G5, which suppresses the immune response; the expression levels of transcription factor Forkhead box-P3 expressed in regulatory T-lymphocytes and Cluster of Differentiation (CD)14 genes, which are thought to be biomarkers in various infectious diseases and expressed in monocytes, will be measured from peripheral blood samples obtained from liver transplant patients before, 1 month and 6 months after the operation. In addition, the classical liver markers Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Platelet Count (PLT), Alpha Feto Protein (AFP), Direct Bilirubin (Bilirubin D), Total Bilirubin (Bilirubin T) and C- Levels of biochemical parameters such as Reactive Protein (CRP) will be measured. In the light of the data to be obtained, it is aimed to find biomarkers with high predictive value for rejection and infection after liver transplantation.

Study Overview

• Status: Active, not recruiting
• Conditions: Infections; Immune Response; Liver Transplant; Complications; Gene Amplification
• Intervention / Treatment: Genetic: Molecular Immunology , gene expressions

Detailed Description

Liver transplantation is the transplantation of the liver, which is completely or partially removed by surgical intervention, from a living or brain-dead cadaver to the recipient. Today, organ transplantation procedures are carried out successfully in many centers in our country.Liver transplantation has become the most effective treatment method for acute and chronic liver failure due to different reasons.The life expectancy of individuals with advanced liver disease, which was limited to months before liver transplantation, was extended with liver transplantation and the quality of life was improved with this treatment method. However, since most of the organ transplants are made from genetically different donors, tissue compatibility between the donor and the recipient remains a problem.Therefore, the recipient's immune response to donor graft antigens should be considered.

In recent years, the application of advanced surgery and new immunosuppressive approaches has made it possible to successfully transplant almost any vital organ or tissue. However, due to both infection and genetic factors, an immune response to the donor organ may develop and cause organ rejection. At this point, we think that early diagnosis and discovery of immune response parameters that distinguish infection from rejection may be important.In our study, some inflammatory Interleukin-2 , Interleukin-6, Interferon-γ, Tumor Necrosis Factor-α and anti-inflammatory Interleukin-4 and Interleukin-10 cytokine genes expressions and Triggering Receptor Expressed on Myeloid Cells-1, which contributes to the pathology of acute and chronic inflammatory diseases; Human Leukocyte Antigen-G5, which suppresses the immune response; the expression levels of transcription factor Forkhead box-P3 expressed in regulatory T-lymphocytes and Cluster of Differentiation (CD)14 genes, which are thought to be biomarkers in various infectious diseases and expressed in monocytes, will be measured from peripheral blood samples obtained from liver transplant patients before, 1 month and 6 months after the operation. In addition, the classical liver markers Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Platelet Count (PLT), Alpha Feto Protein (AFP), Direct Bilirubin (Bilirubin D), Total Bilirubin (Bilirubin T) and C- Levels of biochemical parameters such as Reactive Protein (CRP) will be measured. In the light of the data to be obtained, it is aimed to find biomarkers with high predictive value for rejection and infection after liver transplantation.

• Study Type: Observational
• Enrollment (Anticipated): 54

Contacts and Locations

Study Locations

• Turkey
  • Malatya, Turkey, 44100
    • Inonu University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

It includes patients who do not disrupt their pre- and post-transplant controls and treatment process, among patients with suitable liver disease, among those whose transplantation decision has been taken in accordance with the protocols of İnönü University Liver Transplantation Institute.

Description

Inclusion Criteria: Healthy volunteers without acute or chronic diseases

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Exclusion Criteria: without acute or chronic bacterial and viral infections; Anti-Hepatitis-C (+), HBsAg (+), Anti-HIV (+), renal failure, neutropenia, using immune supressor medications, autoimmunity (+), acute or chronic pancreatitis, being treated with burns, pregnant, using steroid medications, diabetic patients, any malignancy has been identified and treated.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control; Healthy 13 female 14 male subjects	Genetic: Molecular Immunology , gene expressions; Expression levels of inflammatory and anti-inflammatory genes; Other Names: Diagnostic test
Transplantation Patients; 10 female, 17 male subjects	Genetic: Molecular Immunology , gene expressions; Expression levels of inflammatory and anti-inflammatory genes; Other Names: Diagnostic test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical parameters	ALT, AST, PLT, AFP, Bilirubin Direct, Bilirubin Total, CRP levels of all subject in control and Transplantation groups before surgery.	1st month
Gene expression parameters before surgery	Expression levels of Interleukin-2, Interleukin-6, Interferon-gamma, Tumor Necrosis Factor-alpha, Interleukin-4, Interleukin-10, Triggering Receptors Expressed on Myeloid Cells-1, Human Leukocyte Antigen-G5, Forkhead box p3 and Cluster of Differentiation (CD)14 in peripheral blood samples	1st month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene Expression parameters after surgery	Expression levels of Interleukin-2, Interleukin-6, Interferon-gamma, Tumor Necrosis Factor-alpha, Interleukin-4, Interleukin-10, Triggering Receptors Expressed on Myeloid Cells-1, Human Leukocyte Antigen-G5, Forkhead box p3 and Cluster of Differentiation (CD)14 in peripheral blood samples	2nd-3rd months
Gene Expression parameters after surgery	Expression levels of Interleukin-2, Interleukin-6, Interferon-gamma, Tumor Necrosis Factor-alpha, Interleukin-4, Interleukin-10, Triggering Receptors Expressed on Myeloid Cells-1, Human Leukocyte Antigen-G5, Forkhead box p3 and Cluster of Differentiation (CD)14 in peripheral blood samples	4-6th months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiological analysis	Culture analysis in urine and blood samples	1st-6th months

Collaborators and Investigators

• Sponsor: Inonu University
• Collaborators: Anadolu University

Publications and helpful links

General Publications

• Carvalho-Gaspar M, Billing JS, Spriewald BM, Wood KJ. Chemokine gene expression during allograft rejection: comparison of two quantitative PCR techniques. J Immunol Methods. 2005 Jun;301(1-2):41-52. doi: 10.1016/j.jim.2005.03.003. Epub 2005 Apr 1.
• Friedman BH, Wolf JH, Wang L, Putt ME, Shaked A, Christie JD, Hancock WW, Olthoff KM. Serum cytokine profiles associated with early allograft dysfunction in patients undergoing liver transplantation. Liver Transpl. 2012 Feb;18(2):166-76. doi: 10.1002/lt.22451.
• Hassan L, Bueno P, Ferron-Celma I, Ramia JM, Garrote D, Muffak K, Barrera L, Villar JM, Garcia-Navarro A, Mansilla A, Gomez-Bravo MA, Bernardos A, Ferron JA. Early postoperative response of cytokines in liver transplant recipients. Transplant Proc. 2006 Oct;38(8):2488-91. doi: 10.1016/j.transproceed.2006.08.054.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2023
• Primary Completion (Anticipated): December 3, 2023
• Study Completion (Anticipated): December 25, 2023

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2021/24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study protocol, statistical analysis plans can be shared
• IPD Sharing Time Frame: For 2 years
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No