Abstract
The majority of liver grafts exhibit abnormal histological findings late after transplantation, even when liver enzymes are normal. Such subclinical graft injuries were associated with rejection and fibrosis progression in recent studies. The identification of non-invasive biomarkers for subclinical graft injury might help to individualize immunosuppression. Therefore, graft injury was assessed in 133 liver biopsies with normal/near normal liver enzymes from a prospective liver biopsy program. Cytokeratin-18 cell death marker (M65) and donor specific anti-HLA antibodies (DSA) were measured as non-invasive markers in paired plasma samples in addition to routine parameters. M65 was associated with subclinical graft injury but this association was too weak for reasonable clinical application. DSA positivity was associated with more graft inflammation (OR = 5.4) and more fibrosis (OR = 4.2). Absence of DSA excluded fibrosis in 87–89%, while presence of DSA excluded histological criteria for immunosuppression minimization attempts in 92–97%. While CK18 cell death marker had no diagnostic value for the detection of subclinical liver graft injury, DSA testing can help to preselect patients for immunosuppression reduction in case of DSA negativity, while DSA positivity should prompt elastography or liver biopsy for the assessment of subclinical graft injury.
Highlights
The majority of liver grafts exhibit abnormal histological findings late after transplantation, even when liver enzymes are normal
The aim of this study was to analyze the predictive capacities of non-invasive blood markers for histological findings with relevance for the individual immunosuppression management
133 liver biopsies were taken while liver enzymes were within these limits (Fig. 1A)
Summary
The majority of liver grafts exhibit abnormal histological findings late after transplantation, even when liver enzymes are normal Such subclinical graft injuries were associated with rejection and fibrosis progression in recent studies. An individualization of immunosuppression promises a better balance of necessary control of alloreactivity and side effects of immunosuppressants Approaches for such a personalized medicine are safer after Ltx than after other solid organ transplants, because of lower rates of chronic and antibody-mediated rejection and the highest rates of spontaneous operational tolerance. The current gold standard for the detection of subclinical graft injury, could fill this gap of sensitivity, but lack specificity, because subclinical histological abnormalities are found in the majority of livers allografts late after transplantation even in patients with a stable long term course[2,3,4]. A first consensus document describing pattern of chronic antibody-mediated rejection (cAMR) after Ltx was p ublished[7]
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