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

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

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.

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