Invasive fungal infection after liver transplantation: Risk factors and significance of immune cell function monitoring

Abstract

OBJECTIVE:Monitoring immune status in transplant recipients is essential for predicting the risk of infections. The aims of the study were to identify the correlation of a low ImmuKnow adenosine triphosphate (ATP) value with the development of invasive fungal infections (IFIs) and whether this is an independent risk factor for IFIs in liver recipients. METHODS:We followed up 248 liver recipients who developed 157 infectious episodes. Peripheral CD4 + T cells were selected freshly for ATP detection. Percentages of T-helper (Th, CD3+ CD4 + ) and Tsuppressor (Ts, CD3 + CD8 + ) lymphocyte subgroups were also examined. RESULTS:Overall 44 patients (17.7%) were diagnosed as IFIs, of whom 9 (20.5%) died. The average ImmuKnow ATP value in the IFI patients (109 Ϯ 78 ng/mL) was significantly lower than that in common bacterial infections (174 Ϯ 106 ng/mL, P < 0.01) or stable liver recipients (314 Ϯ 132 ng/mL, P < 0.01), while there was no difference in the Th/Ts ratio among each group. Logistic regression analysis showed ImmuKnow ATP value less than 100 ng/mL was an independent risk factor of IFI (OR = 3.44, P = 0.0237). ImmuKnow ATP values had no correlation with lymphocytes or their subgroups, but tended to correlate with the number of neutrophils and total white blood cells. CONCLUSIONS:ImmuKnow assay monitoring has the potential to identify the patients at risk of developing IFI after liver transplantation (LT), which may provide a feasible measure for optimizing liver recipients' immune cellular function after transplantation.

Clinical immune‐monitoring strategies for predicting infection risk in solid organ transplantation

“…76 Interestingly, iATP levels show a poor correlation with calcineurin inhibitor trough levels, total lymphocyte count or Th 1 /Th 2 ratio. 76, 77, 78, 79 Numerous authors have analyzed the predictive value of iATP for acute rejection, as recently summarized in a meta-analysis that found a relatively high specificity (0.75) but a low sensitivity (0.43), with significant heterogeneity across studies. 73 The occurrence of post-transplant infection was also included as a primary outcome in most of these studies, encompassing kidney, 80, 81, 82 liver, 79, 83 heart 77, 84 and lung 78, 85 transplant populations.…”

“…73 A second meta-analysis focused only on liver transplant recipients reported better performance values (0.83 and 0.75, respectively). 74 The utility of this approach has been also assessed for predicting some specific entities—including CMV and EBV infection, 86 polyomavirus BK-associated nephropathy 81 or invasive fungal infection 79 —usually in single-center studies with small sample sizes. A further application of the ImmuKnow assay could be predicting the progression from fungal colonization to invasive infection.…”

Peripheral blood CD 4 + cell ATP activity measurement to predict HCC recurrence post‐ DCD liver transplant

“…ImmuKnow does not correlate with CD4 + cell numbers, and the assay is theorised to provide an independent variable . Studies in orthotopic liver transplantation (OLT) recipients have reported contradictory results with ImmuKnow . Most of these studies were retrospective, had limited follow‐ups, were heterogeneous in study design, and often included multiple solid organ transplants in the analysis, despite immunosuppression protocols and clinical event risks differing substantially among different transplant populations.…”

“…IL-1b values and IL-17A concentrations from HCC recurrence LTs showed no difference from those from the stable LTs (C, D) Figure 4 In ROC analysis, the AUC was 0.73, and the optimum cut-off value was 276 ng/ml for recurrence Figure 5 Survival difference between the groups of HCC patients after liver transplantation with high-and low immune responses. A superior recurrence-free survival rate (p < 0.05) was observed in the high immune response group, compared with the low immune response group contradictory results with ImmuKnow (9)(10)(11)(12)(13)(14)(15). Most of these studies were retrospective, had limited follow-ups, were heterogeneous in study design, and often included multiple solid organ transplants in the analysis, despite immunosuppression protocols and clinical event risks differing substantially among different transplant populations.…”

Cutaneous presentation of progressive disseminated histoplasmosis nine years after renal transplantation

“…Careful monitoring of immunosuppressant dosing and serum levels is important to avoid renal allograft compromise by either rejection or toxicity. Routine surveillance immune monitoring by Immuknow ® assay has been reported in liver transplant recipients as having the potential to identify patients at risk of developing IFIs . However, no data report if this assay can predict the risk of rejection in the setting of an active or recent fungal infection by post‐infection monitoring follow‐up and repeat measurements of the assay.…”