Understanding Acute Cellular Rejection (ACR)

Acute Cellular Rejection (ACR) occurs when the recipient’s immune system attacks and rejects cells from the transplanted organ, a common complication following liver transplantation (LTx). Diagnosis traditionally relies on invasive liver biopsies, which have a limited ability to provide early prognostic information before rejection occurs.

A Noninvasive Alternative for Diagnosis

The development of noninvasive diagnostics via liquid biopsy represents a major advancement in personalized care for transplant recipients. Liquid biopsy involves analyzing predictive biomarkers, such as cell-free microRNAs (miRNAs), in blood samples. This minimally invasive approach offers an attractive alternative for diagnosing ACR.

miRNAs and the HepatoTrack Test

Through collaborative research, we have identified a panel of miRNA biomarkers capable of predicting ACR with high specificity and sensitivity. The HepatoTrack test has demonstrated diagnostic utility in detecting ACR up to 40 days before biopsy-confirmed rejection.* This predictive capability enables routine surveillance of liver allograft health, rather than limiting monitoring to times of suspected dysfunction, highlighting its potential clinical value.

Clinical Utility: Optimizing Immunosuppression Management

Post-transplant immunosuppression regimens typically involve a combination of corticosteroids, calcineurin inhibitors, and antimetabolites. Corticosteroids are tapered off within the first few months, but most patients require lifelong immunosuppressive therapy. The challenge lies in minimizing drug toxicity while maintaining effective immunosuppression. Currently, there is no noninvasive, highly prognostic method to monitor liver health during immunosuppressive therapy adjustments. HepatoTrack addresses this gap by enabling real-time evaluation of liver health during dose optimization. This includes guiding reductions in antimetabolite use and fine-tuning calcineurin inhibitor dosing, ultimately improving patient outcomes while reducing the risk of drug-related side effects.

*Reference: Shaked A, et al. An ectopically expressed serum miRNA signature is prognostic, diagnostic, and biologically related to liver allograft rejection. Hepatology. 2017 Jan;65(1):269-280. doi: 10.1002/hep.28786. Epub 2016 Oct 5. PMID: 27533743.