The Role Of Combined Gene Expression Profiling And Donor-derived Cell-free Dna In Differentiating Acute Rejection In Liver Transplant Recipients
1Transplant nephrology, Northwestern University, Chicago, IL, 2Northwestern University, Chicago, IL, 3Eurofins Viracor, Lee's Summit, MO, 4Eurofins Viracor, Lee's summit, MO, 5University of Arizona, Tucson, AZ, 6Northwestern University Feinberg School of Medicine, Chicago, IL
Meeting: 2022 American Transplant Congress
Abstract number: 9083
Keywords: Genomic markers, Lung transplantation, Rejection
Topic: Basic Science » Basic Clinical Science » 17 - Biomarkers: Clinical Outcomes
Session Information
Session Name: Biomarkers: Clinical Outcomes
Session Type: Poster Abstract
Date: Tuesday, June 7, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: In our previous studies, blood-based gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) have been independently validated in liver transplant recipients (LTR) to ‘rule-out’ acute rejection (AR) with high negative predictive value (NPV). However, the positive predictive value (PPV) (‘rule-in’ AR) of either test alone was insufficient. We hypothesized that combining GEP and dd-cfDNA could augment the PPV and retain high NPV, allowing for a more complete diagnostic test.
*Methods: We performed a post hoc analysis of available GEP and dd-cfDNA data from previously reported single center (NU: 2010-2015, 2019-2020) and multicenter trial (CTOT14: 2012-2014). Clinical diagnostic LTR phenotypes were defined as 1) AR: biopsy proven rejection by “for cause biopsy”, 2) acute dysfunction no rejection (ADNR): no rejection (other etiology) by “for cause biopsy”, and 3) TX: long standing normal liver function tests. The non-AR group included ADNR and TX. The samples at biopsy were randomly divided into training and test set for a 70:30 approach. The GEP and dd-cfDNA values were used to conduct area under the curve (AUC) analysis and calculate sensitivity, specificity, PPV, NPV and accuracy.
*Results: A total of 51 AR and 159 non-AR samples were analyzed. The training set consisted of 35 of AR and 109 of non-AR including ADNR (n=47) and TX (n=62). In the test set, the sample size was 16 and 50 (ADNR=20, TX=30), AR and non-AR, respectively. The AUC in the test set for GEP and dd-cfDNA alone to differentiate AR vs. non-AR were 0.94 and 0.87, respectively. When GEP and dd-cfDNA were combined, the AUC was 0.96 (Table 1). The diagnostic performances of GEP alone were PPV 0.81, NPV 0.92, and balanced accuracy 0.85. dd-cfDNA showed PPV 0.88, NPV 0.80, and balanced accuracy 0.77. Combining the two analyses resulted in PPV 0.88, NPV 0.92, and balanced accuracy 0.87 (Table 1).
*Conclusions: The combination of GEP and dd-cfDNA allows for higher PPV, while maintaining high NPV, than each test alone in LTR. At the ATC, we will report the serial trend of combined GEP and dd-cfDNA preceding and following AR. These results suggest that combining GEP and dd-cfDNA results could be useful for diagnosing and excluding AR non-invasively and monitoring for AR during immunosuppression tapering.
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To cite this abstract in AMA style:
Park S, Kandpal M, Guo K, Kleiboeker S, Sinha R, Abecassis M, Levitsky J. The Role Of Combined Gene Expression Profiling And Donor-derived Cell-free Dna In Differentiating Acute Rejection In Liver Transplant Recipients [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/the-role-of-combined-gene-expression-profiling-and-donor-derived-cell-free-dna-in-differentiating-acute-rejection-in-liver-transplant-recipients/. Accessed November 21, 2024.« Back to 2022 American Transplant Congress