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Observational Study
. 2025 Feb 18;29(1):79.
doi: 10.1186/s13054-025-05305-x.

Individual mHLA-DR trajectories in the ICU as predictors of early infections following liver transplantation: a prospective observational study

M C Delignette  1   2   3   4 , A Riff  2   3   4   5 , T Antonini  2   5 , T Soustre  1   2 , M Bodinier  3 , E Peronnet  3 , F Venet  3   4   6   7 , M Gossez  3   4   6   7 , S Pantel  2   8 , J Y Mabrut  2   4   9   10 , X Muller  2   4   9   10 , K Mohkam  2   4   9   10 , F Villeret  2   4   5   9 , D Erard  2   4   5   9 , J Dumortier  2   4   11 , F Zoulim  2   4   5   9 , L Heyer  1 , C Guichon  1   2 , A Blet  1   2   4   9 , F Aubrun  1   2   4 , G Monneret  2   3   4   6 , F Lebossé  12   13   14   15
Affiliations
Observational Study

Individual mHLA-DR trajectories in the ICU as predictors of early infections following liver transplantation: a prospective observational study

M C Delignette et al. Crit Care. .

Abstract

Background: Infections are a leading cause of early mortality after liver transplantation (LT). Prior to transplantation, cirrhosis-associated immune dysfunction significantly increases the risk of infection. This study investigated the potential of immune monitoring, with a focus on monocytic HLA-DR (mHLA-DR) expression, as a predictor of post-LT complications.

Methods: We conducted a prospective study on 130 patients awaiting LT at Lyon University Hospital to assess mHLA-DR expression, lymphocyte subsets, and T-cell function before and after LT. Multivariate analysis and K-means longitudinal clustering were performed to explore the relationships between immune trajectories and clinical outcomes.

Results: Among the 99 patients who underwent LT, 35.4% experienced infections early post-LT. No difference in outcome was found regarding lymphocyte count or function. Delayed mHLA-DR recovery (Day 7 < 11,000 AB/C) and pre-LT MELD scores > 30 emerged as independent infection risk factors, with ORs of 12.1 [4.4-38.2], p < 0.0001 and 4.9 [1.4-18.4], p = 0.01, respectively. Patients with delayed mHLA-DR restoration also had reduced one-year survival (77.8% versus 98.3%, p = 0.003). K-means clustering revealed three distinct mHLA-DR recovery profiles, with the slowest recovery group showing the poorest outcomes.

Conclusions: Our findings highlight mHLA-DR as an early predictor of post-LT infections. Monitoring post-LT immune function through mHLA-DR expression could guide individualized management strategies to improve outcomes. Trial registration The study was registered in the ClinicalTrials.gov registry: NCT03995537, date: June 20, 2019.

Keywords: ICU; Immune dysfunction; Immune monitoring; Infections; Liver transplantation; MHLA-DR; Transplant outcomes.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by the Comité de Protection des Personnes Ile de France XI (approval number 19039-40433). Written informed consent was obtained from all participants prior to enrollment. The study complied with the Declaration of Helsinski. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Consent for publication: Not applicable. Competing interests: MB and EP are employees of BioMérieux SA, an in vitro diagnostic company. MCD, MB, EP, FV, MG and GM work in a joint research unit, co-funded by the Hospices Civils de Lyon and bioMérieux.

Figures

Fig. 1
Fig. 1
Flow chart showing outcomes following enrolment in the study
Fig. 2
Fig. 2
Evolution of immune markers after liver transplantation (LT). Monocyic expression of HLA-DR expressed as an antibody by cells (A), total lymphocytes (B), T lymphocytes (C), CD4 lymphocytes (D), CD8 lymphocytes (E) and T lymphocyte function according to the interferon‒gamma release assay aftr stimulation, expressed as the reference fluorescence value (F). The dotted lines represent the lower and upper limits of normal values previously reported for healthy volunteers. AB/C: antibodies per cell, LT: liver transplantation, mHLA-DR: monocytic HLA-DR, RFV: reference fluorescence value
Fig. 3
Fig. 3
Monocytic expression of HLA-DR (mHLA-DR) after liver transplantation (LT) and post-LT outcomes. Evolution of mHLA-DR according to the occurrence of infection (A) and survival without infection according to D5-7 mHLA-DRa (B). Evolution of monocytic expression of HLA-DR after liver transplantation (LT) according to one-year survival (C). One-year survival according to D10 mHLA-DRb (D). AB/C: antibodies per cell, LT: liver transplantation, mHLA-DR: monocytic HLA-DR; dotted lines represent the lower (i.e., 13,500 AB/C) and upper (i.e., 45,000 AB/C) limits of normal values. The Mann‒Whitney U test was used for comparisons. Survival curves were generated via Kaplan‒Meier estimates, and differences were compared via the log-rank test. *p < 0.05, **p < 0.10, ***p < 0.001, ****p < 0.001. a Survival curves generated in 95 out of 99 patients in whom D5-7 mHLA-DR was available. b Survival curves generated in 86 out of 99 patients in whom D10 mHLA-DR was available
Fig. 4
Fig. 4
Monocytic expression of HLA-DR trajectories post-liver transplantation and their impact on survival outcomes. A Trajectory of mHLA-DR expression after LT according to unsupervised clustering with the KmL method in the LT group (n = 96). The shaded interval corresponds to the normal values previously reported for healthy volunteers. B One-year survival according to the mHLA-DR endotype. C One-month survival without infections according to the mHLA-DR endotype. Ab/cell: antibodies per cell, KmL: k-means for longitudinal data, LT: liver transplantation, mHLA-DR: monocytic HLA-DR
See this image and copyright information in PMC

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