P2921 - To Biopsy or Not to Biopsy: A Cochrane Diagnostic Meta-Analysis of Non-Invasive Biomarkers for Acute T-Cell Mediated Liver Transplant Rejection

Kevin Brittan, MD¹, Alexandra Fiedler, MD¹, Busara Songtanin, MD², Kyle Scholten, DO¹, Shane Manatsathit, MD^3
1University of Nebraska Medical Center, Omaha, NE; ²Texas Tech University Health Sciences Center, Lubbock, TX; ³CHI Health Creighton University Medical Center, Omaha, NE

Introduction: Acute t-cell-mediated liver transplant rejection (TCMR) occurs in 16 to 27% of liver transplants. It is challenging to differentiate between rejection and other forms of graft dysfunction. Therefore, a liver biopsy is often required to determine the etiology of graft dysfunction. Various biomarkers have been evaluated to determine the feasibility of non-invasive methods to determine acute liver transplant rejection. In a diagnostic meta-analysis, we aim to evaluate Cell-Free DNA (CF DNA), micro-RNA (miRNA), and soluble IL-2 to assess performance in acute liver transplant rejection.

Methods: A literature search was performed in EMBASE, Scopus, CINAHL, and Medline with keywords relating to acute liver transplant rejection and biomarkers. Data collection was performed by three independent collectors (K.B., A.F., S.S.). The quality of studies was evaluated using the QUADAS-2. Pooled sensitivity, log diagnostic odds ratio, and area under the summary receiver operating characteristic curve (AUC) were calculated along with subgroup and sensitivity analyses.

Results: Five CF DNA, seven miRNA, and five IL-2A studies were included. A total of 1436 patients were included with 340 TCMR. CF DNA had a sensitivity of 0.89 CI [0.83,0.96], specificity of 0.92 CI [0.87,0.97], LDOR of 4.07, AUC of 0.888. The subgroup of CF DNA that used a percentage-based threshold had a sensitivity of 0.90 CI [0.83,0.97], specificity of 0.90 CI[0.85,0.95], LDOR of 4.24, and AUC of 0.917. MiRNA had a sensitivity of 0.86 CI [0.80,0.92], specificity of 0.88 CI [0.80,0.97], LDOR of 3.62, and AUC of 0.897. Subgroup analysis for miRNA 155 had a sensitivity of 0.88 CI [0.80,0.95], specificity of 0.91 [0.81,1.00], LDOR of 4.09, and AUC of 0.861. IL-2 had a sensitivity of 0.86 CI [0.79,0.93], specificity of 0.87 CI [0.78,0.96], LDOR of 3.69, and AUC of 0.905.

Discussion: This meta-analysis demonstrates that all CF DNA, miRNA, and IL-2 are excellent non-invasive tests for the diagnosis of TCMR. There was no significant superiority of one test to another, given the variance in test performances. However, only two subgroups were exceptional diagnostic tests by multivariant analysis: the percentage-based CF DNA subgroup and IL-2. The percentage-based CF DNA subgroup performed best with a sensitivity of 0.90, specificity of 0.90, and AUC of 0.917. All three tests demonstrated exceptional performance for diagnosing TCMR, with percentage-based CF DNA having non-significantly superior performance.


Disclosures:


Kevin Brittan, MD¹, Alexandra Fiedler, MD¹, Busara Songtanin, MD², Kyle Scholten, DO¹, Shane Manatsathit, MD³. P2921 - To Biopsy or Not to Biopsy: A Cochrane Diagnostic Meta-Analysis of Non-Invasive Biomarkers for Acute T-Cell Mediated Liver Transplant Rejection, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.