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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cirrhosis; Liver; Acute Hepatitis; mHLA-DR
• Intervention / Treatment: Biological: blood sampling; Biological: Biocollection

• Study Type: Observational
• Enrollment (Estimated): 279

Contacts and Locations

• Study Contact: Name: LEBOSSE Fanny, Dr; Phone Number: +33 4 26 10 93 39; Email: fanny.lebosse@chu-lyon.fr
• Study Contact Backup: Name: DELIGNETTE Marie Charlotte, Dr; Phone Number: +33 4 26 10 90 70; Email: marie-charlotte.delignette@chu-lyon.fr

Study Locations

• France
  • Clermont-Ferrand, France, 63100
    • Department of Hepatology and Gastroenterology - CHU de Clermont Ferrand
    • Contact: Abergel Armand, Pr; Phone Number: +33 4 73.75.05.04; Email: aabergel@chu-clermontferrand.fr
  • Lyon, France, 69004
    • Department of Hepatology and Gastroenterology - Hôpital de la Croix-Rousse
    • Contact: LEBOSSE Fanny, Dr; Phone Number: +33 4 26 10 93 39; Email: fanny.lebosse@chu-lyon.fr
    • Contact: DELIGNETTE Marie-Charlotte, Dr; Phone Number: +33 4 26 10 90 70; Email: marie-charlotte.delignette@chu-lyon.fr
  • Montpellier, France, 34090
    • Department of Hepatology and Gastroenterology - Hôpital Saint Eloi
    • Contact: Bedoya Jose Ursic, Dr; Phone Number: 33 4 67.33.70.62; Email: jose.ursicbedoya@chu-montpellier.fr
    • Contact: Monet Clément, Dr; Phone Number: +33 4 67.33.02.62; Email: c-monet@chu-montpellier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study 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.

Description

Inclusion Criteria:

Patients awaiting liver transplantation for one of the following indications:

• 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

Final inclusion will be :

• Patients receiving LT AND
• Who provided their consent to participate during the initial enrollment visit AND
• For whom the baseline sample (during the day of the LT) was collected

Exclusion Criteria:

• Minors
• Patients under legal guardianship or conservatorship
• Pregnant or breastfeeding women
• Patients deprived of their liberty
• Patients not enrolled in the social security system
• Refusal to participate in the study
• Patients receiving immunosuppressive therapy prior to LT (with the exception of corticosteroids at a dosage of 40 mg per day for the treatment of alcoholic hepatitis)
• Patient who is a candidate for a combined organ transplant
• Patient receiving other immunomodulatory therapy (such as immune checkpoint inhibitors) prior to LT

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with severe liver disease waiting for liver transplantation; 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 and fulminant hepatitis

Biological: blood sampling; 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; Biological: Biocollection; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive score for the risk of infectious complications	The primary endpoint will be the sensitivity and specificity of a predictive score for the risk of early post-Liver Transplant (LT) infectious complications (30 days post-LT) in a population of patients undergoing LT for standard indications (cirrhosis complicated by HCC, decompensated cirrhosis, acute hepatitis). The predictive score will be based on baseline (Day 0), Day 1, Day 3, Day 5, and Day 10 mHLA-DR levels, the pre-LTP MELD score, and/or other clinical or laboratory parameters significantly associated with the risk of infection.	Day 30

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: June 10, 2026
• First Submitted That Met QC Criteria: June 10, 2026
• First Posted (Actual): June 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Cirrhosis; liver; Acute hepatitis; mHLA-DR
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fibrosis; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 69HCL25_1061

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