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Active, Not Recruiting

NCT Number: NCT02784080

Donor Specific HLA Alloantibodies in Liver Transplantation

The aim is to evaluate the impact of donor specific HLA alloantibodies (DSA) on all-cause mortality and re-transplantation, early allograft dysfunction, acute and chronic rejection, fibrosis, vascular, and biliary complications. Furthermore, all biopsies will be C4d stained. The hypothesizes is that donor specific HLA alloantibodies facilitate an immune mediated damage to the liver allograft that impairs function and lead to various complications.

The investigators will do a prospective blinded multicenter cohort study in the Scandiatransplant organ sharing organization region.

Both preformed, persistent, and de novo donor specific HLA alloantibodies will studied. Blood samples will be taken immediately prior to transplantation, and 14 days, 3 months, and 1 year after transplantation. All liver biopsies performed during the study period will be evaluated for a humoral component and blood samples will be obtained prior to liver biopsies to investigate the presence of DSA.

Investigations will be fully blinded for the treatment responsible doctors.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Complication of Transplanted Liver Behavior Fibrosis Pathologic Processes Pathological Conditions, Signs and Symptoms Rejection, Psychology Social Behavior

Sex eligibility

All sexes

Study type

Observational

Primary location

Department of Surgical Gastroenterology and Transplantation, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark

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About this study

The outcome after liver transplantation has improved drastically over time, but this development has stagnated in recent years to a graft failure rate of 9-15 % within the first year and approximately 20-30 % at 5 years [1]. The primary goal is to improve the outcome after liver transplantation.

The impact of donor specific antibodies (DSA) on all-cause mortality and re-transplantation, early allograft dysfunction, acute and chronic rejection, vascular and biliary complications and fibrosis will be investigated.

Objectives:

  • The primary objective is to investigate if DSA both pre-formed, persistent, and de novo affect survival and allograft loss. For patients diagnosed with HLA antibodies a standard Luminex single antigen IgG analysis, a Luminex C1q and an IgG3 single antigen assay will be performed.
  • The secondary objective is to investigate if donor specific antibodies, both pre-formed, persistent, and de novo increase the risk of early allograft dysfunction, acute and chronic rejection, fibrosis, de novo autoimmune hepatitis (pediatric patients only), vascular and biliary complications. All liver biopsies will be stained by C4d and a DSA analysis will be undertaken.
  • Continuous measurements will be used to establish the kinetics of both preformed og de novo DSA after liver transplantation.

Pediatric patients will be analyzed separately.

In 2021 it was decided to split the study in a preformed and de novo study.

Preformed DSA

  • Our primary objective is to investigate if preformed and persistent DSA class I and II affect survival and re-transplantation.
  • The secondary objective is to investigate if preformed and persistent DSA class I and II is correlated with increased risk of acute rejection and early allograft dysfunction.

Preformed DSA will be analysed in 4 different ways separately for donor specific HLA class I and class II antibodies.

  • Dichotomous analysis defined as any DSA class I or II MFI >1000 is considered positive.
  • Number of different class I or II DSA will be analyzed as an ordinal variable.
  • A continuous variable by MFI, as a sum of all. Homozygous donors will not be accounted for.
  • Analysis will be done for no antibodies versus: 1) HLA-DQ (including DRB5 subtypes) 2) HLA-DR 3) HLA-DQ and -DR. Both as categorical and binary.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Undergo a liver transplanted during the study period.
  • Pre-transplant serum sample of minimum 4 ml (relevant for pediatric patients)
  • Informed consent is given.

Exclusion criteria

  • Withdrawal of informed consent.
  • Blinding broken in a non-protocoled manner the patient will be excluded.

Treatment and study plan

HLA-alloantibodies exposure

Other

Following analyzes will be done:

LABScreen® Single Antigen, One Lambda, CA

C1qScren™, One Lambda, CA (planned for later study)

PE-conjugated IgG3 antibody (planned for later study)

LABScreen® Mixed, One Lambda, CA (never analysed in the study)

Primary outcomes

  1. All-cause mortality or re-transplantation (graft loss)

    Time frame: Minimum 1 year, accrual to study end

Secondary outcomes

  1. Early allograft dysfunction are defined as total bilirubin >10 mg/dl or INR >1.6 at day 7 after liver transplantation or ALT >2000 IU/L within the first 7 days after liver transplantation.

    Time frame: 7 days after transplantation

  2. Acute rejection, both cellular and humoral rejection, as defined by Banff classification.

    Time frame: Minimum 1 year, accrual to study end

  3. Chronic rejection, as defined by Banff classification, and as proposed by O'leary et al "Proposed Diagnostic Criteria for Chronic Antibody-Mediated Rejection in Liver Allografts".

    Time frame: Minimum 1 year, accrual to study end

  4. Fibrosis, defined by METAVIR score.

    Time frame: Minimum 1 year, accrual to study end

  5. Vascular complications (hepatic arterial stenosis, hepatic arterial thrombosis, portal vein thrombosis).

    Time frame: Minimum 1 year, accrual to study end

  6. Biliary complications (biliary leakage, anastomotic biliary stricture, non-anastomotic biliary stricture, liver abscess, cholangitis, other).

    Time frame: Minimum 1 year, accrual to study end

    Anastomotic strictures and non-anastomotic strictures will be investigated as a combined and solitary outcome.

Sponsors and collaborators

Lead sponsor

Rigshospitalet, Denmark

Other

Collaborators

  • Helsinki University Central Hospital
  • Karolinska Institutet
  • Oslo University Hospital
  • Sahlgrenska University Hospital

Registry information

Official study title

Donor Specific HLA Alloantibodies in Liver Transplantation: a Prospective Blinded Multicenter Prognostic Study

Important dates

Study start
2015
Primary completion
2024
Study completion
2024
First posted
May 26, 2016
Registry last updated
Sep 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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