Development of a Predictive Score for the Risk of Infection in the Immediate Post-liver-transplant Period

Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorHospices Civils de Lyon

About this trial

Liver transplantation (LT) is the only curative treatment option for patients with severe liver disease. Since 2007, the implementation of the MELD score in liver transplant allocation guidelines has led to a change in the profile of transplant recipients, notably with an increase in the proportion of patients receiving transplants for severe liver failure. Thus, in 2023, nearly 40% of liver transplant recipients whose primary indication for LT was cirrhosis had a MELD score greater than 35 (ABM Scientific Report 2023). These patients with severe pre-transplant liver failure often present with associated organ failure (Acute-on-Chronic Liver Failure, ACLF). Infections are the leading cause of death at 1 year post-transplant for patients transplanted with ACLF and are a major concern for all patients, representing one of the leading causes of death at 3 months post-transplant. Another common complication following LT is acute cellular rejection. Although frequent, this complication is reversible with treatment and results in graft loss in fewer than 5% of cases.

The expression of the HLA-DR marker by monocytes (mHLA-DR) is correlated with immunoparesis and the risk of secondary infection and mortality in patients admitted to critical care. In a prospective, single-center pilot study of 99 liver transplant recipients, the Hepatology and Gastroenterology service at the Croix Rousse Hospital, Hospices Civils de Lyon, demonstrated that the kinetics of mHLA-DR levels measured immediately after transplantation could predict the risk of early significant infection (\< 1 month) after transplantation and 1-year post-transplant mortality. The early post-transplant kinetics of mHLA-DR expression recovery appeared to be a more relevant predictor of the risk of early post-transplant infection than a single-point-in-time value. The profile of immune recovery kinetics, as well as a pre-LT MELD score \> 30, were associated in multivariate analysis with the risk of developing an infection at 1 month post-LT and with 1-year post-LT survival.

PREDITH study team hypothesize that the implementation of mHLA-DR testing immediately post-LT would enable the development of a predictive score for early post-LT infection combining clinical and biological risk factors for post-LT infection and immune monitoring.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Compensated cirrhosis complicated by hepatocellular carcinoma

Chronically decompensated cirrhosis (recurrent gastrointestinal bleeding, refractory ascites, portopulmonary or hepatopulmonary syndrome, hepatic encephalopathy, chronic liver failure)

Acute decompensated cirrhosis, with or without associated multiple organ failure (ACLF)

Acute fulminant hepatitis

Disqualifiers

Minors

Patients under legal guardianship or conservatorship

Pregnant or breastfeeding women

Patients deprived of their liberty

Trial population

Patients with severe liver disease waiting for LT. Only patients with the most frequent LT indications will be eligible: complicated cirrhosis of hepatocellular carcinoma (HCC), acute or chronic decompensation of cirrhosis, with or without multi-visceral failure and fulminant hepatitis.

Trial design

Design model

Case-control

Time perspective

Prospective

Treatments tested in this trial

  • blood sampling

    Biological/Vaccine

    Samples will be collected at the finale inclusion of the day oh the LT, including one sample of Cyto-Chex BCT (4 millilitre mL) . Same samples will also be collected after LT at days 1,3,5 and 10. Biological data will be collected at those different times

  • Biocollection

    Biological/Vaccine

    For the creation of the biobank one samples of Ethylenediaminetetraacetic acid (EDTA) (4 millilitre (mL)), and one PAXgene® sample (2.5mL) will be collected: * at inclusion before LT * at final inclusion, day of the LT * And at days 1, 3, 5 and 10 after LT

Treatment groups

279 Participants
are divided into 1 treatment group
Group A: Patients with severe liver disease waiting for liver transplantation (LT)2 interventions

Trial outcomes

Primary outcomes

1

Predictive score for the risk of infectious complications

The primary outcome measure will be the diagnostic performance of a predictive score for early post-Liver Transplant (LT) infectious complications occurring within 30 days after LT. The predictive score will be derived from mHLA-DR levels measured at predefined time points (Day 0, Day 1, Day 3, Day 5, and Day 10 post-LT), the pre-transplant MELD score, and other clinical or laboratory variables significantly associated with infection risk. The predic

Time frame
Day 30

Secondary outcomes

Other outcomes

Sponsors and contacts

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