The Role Of Combined Gene Expression Profiling And Donor-derived Cell-free Dna In Differentiating Acute Rejection In Liver Transplant Recipients

S. Park¹, M. Kandpal², K. Guo², S. Kleiboeker³, R. Sinha⁴, M. Abecassis⁵, J. Levitsky⁶

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 May 7, 2025.

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