AGRA Before and After Liver Transplantation

Humoral Immune Status in Patients With Liver Cirrhosis Before and After Liver Transplantation

The immune system is impaired in liver cirrhotic patients, which is associated with a high risk for bacterial infections and worse outcome. A novel biomarker, acellular growth retardation ability (AGRA), can predict the development of severe infections in patients with liver cirrhosis and therefore identify patients at risk. It is still unclear, how this biomarker develops after liver transplantation and how valid its predictions are for post-operative infections. Therefore, AGRA will be measured before and after liver transplantation and predictive merit of AGRA for post-transplant infections will be tested.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Cirrhosis

Detailed Description

Cirrhosis-associated immune dysfunction syndrome (CAIDS) is a well-recognized phenomenon. It affects all immune cells as well as the humoral immune system. Because of this deficiency patients with liver cirrhosis often suffer from severe infections that can be complicated by sepsis, acute renal or liver failure, and lead to prolonged hospitalization and ultimately to the death of the patient. The humoral immune system is a first-line defence mechanism and consists of cell-free molecules that are partly produced by the liver and target pathogens through opsonisation, growth inhibition and lysis. A cirrhotic liver cannot reach its full protein expression capacity and consequently, quantitative and qualitative changes of complement factors and immunoglobulins have been observed in liver disease patients before.

Liver transplantation remains the only curative option to treat liver cirrhosis and its extrahepatic manifestations; however due to limited organ supply this option is not applicable in all cases. Therefore, liver cirrhosis and its complications (eg. infections) need to be managed by health care professionals, who often lack appropriate tools for risk assessment. To meet this clinical need, a novel biomarker was recently established (Acellular Growth Retardation Ability, short AGRA) that uses the state of the humoral immune system to predict the future occurrence of severe infection in liver disease patients. However, it is still unclear how this biomarker develops after liver transplantation and how valid its predictions are for post-operative infections.

Therefore, patients scheduled for liver transplantation will be included in the trial. AGRA measurements before and after the transplant (1, 7, 90 days after the end of antibiotic treatment) will be performed. Additionally outcome data regarding severe infections are collected for one year before and after transplantation. The respective organ donors are included as a control group.

• Study Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Department of Internal Medicine, Medical University of Geraz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients listed for liver transplantation at the University Hospital in Graz, Austria for any reason will be included in the study. The respective donors will serve as a control cohort.

Description

Inclusion Criteria:

• Patients between 18-80 years
• Listed for liver transplantation (for recipients)
• Liver recipient is included in the study (for donors)
• Informed consent

Exclusion Criteria:

• Antibiotic therapy with substances active against E. coli at the scheduled blood sampling

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Test group; Patients undergoing liver transplantation, no intervention (study-specific) is planed
Control Group; Respective organ donors of the included liver recipients, no intervention (study-specific) is planed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Acellular growth retardation ability (AGRA)	Functional biomarker for the state of the humoral immune system	change from transplantation to 90 days after the end of prophylactic antibiotic treatment after the transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infections	Occurrence of severe infections	1 year after transplantation
Infections	Occurrence of severe infections	1 year before transplantation
Complications	Occurrence of transplantation-related complications	during hospital stay
C reactive protein	routine biomarker for infections	change from transplantation to 90 days after the end of prophylactic antibiotic treatment after the transplantation
Liver function	State of the donated liver, including results of a possible liver biopsy prior to transplantation	before transplantation

Collaborators and Investigators

• Sponsor: Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2018
• Primary Completion (Actual): May 31, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: February 19, 2018
• First Submitted That Met QC Criteria: February 23, 2018
• First Posted (Actual): February 26, 2018

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: AGRA-TX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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