Immune Frailty Biomarker Panel Predicts Early Mortality After Liver Transplant: JAMA
Researchers have discovered in a new research that a preoperative biomarker panel can identify liver transplant candidates with severe immune dysfunction who are at high risk of early transplant-related mortality. This panel enables objective risk stratification before surgery, helping clinicians improve patient selection, anticipate complications, and optimize perioperative management to enhance transplant outcomes. The study was published in JAMA Surgery by Guergana G. and colleagues.
The newly developed Liver Immune Frailty Index (LIFI) successfully identified patients undergoing liver transplant (LT) who were at high risk for early post-transplant mortality. The current pretransplant clinical risk stratification tools are inadequate for predicting post-transplant survival. Immune dysfunction is increasingly recognized as a contributing factor to early mortality following liver transplantation. However, current risk stratification models are not able to account for this biological risk. The goal of this study was to discover plasma biomarkers of immune dysfunction and create a risk stratification tool that could predict 1-year post-transplant mortality.
This prospective biomarker analysis enrolled consecutively adult LT recipients and healthy controls. Patients undergoing deceased donor LT for cirrhosis at Houston Methodist Hospital from October 1, 2013, to December 31, 2017, and at Rutgers/University Hospital from January 1, 2019, to March 31, 2021, were enrolled under institutional review board-approved protocols. Data was censored on March 31, 2023.
Inclusion criteria included adults older than 18 years with cirrhosis undergoing deceased donor LT. Exclusion criteria included age > 70 years, malignancy other than hepatocellular carcinoma, retransplant, 1A listing, intraoperative death, multivisceral transplant (except liver and kidney), and unavailability of samples.
Key findings
779 LTs in adults were carried out between 2007 and 2017.
Among these, 279 patients consecutively enrolled underwent prospective biomarker evaluation between 2018 and 2022.
Median (IQR) age was 56.7 (48.2-62.5) years, and 110 patients (39.4%) were female.
Pretransplant plasma fractalkine and MMP3 concentrations independently predicted 1-year mortality.
One-year mortality was 1.9% in LIFI-low, 10.3% in LIFI-moderate, and 63.6% in LIFI-high patients. Risk of death at 1 year was 5.43 (95% CI, 1.59-18.60; P < 0.001) for LIFI-moderate and 33.41 (95% CI, 11.48-97.25; P < 0.001) for LIFI-high compared with LIFI-low.
The model had excellent predictive power with a C statistic of 0.83 and was linked to infections, hospitalization, and was associated with infections, prolonged hospitalization, and decreased survival.
The Liver Immune Frailty Index is a tool that helps to identify patients undergoing liver transplantation who have severe pretransplant immunodeficiency and are at high risk of death shortly after liver transplantation. The development of LIFI represents a promising approach to improve patient selection for liver transplantation and posttransplant survival.
Reference:
Panayotova GG, Simonishvili S, Jin L, et al. Development and Internal Validation of a Pretransplant Biomarker Panel for Mortality Prediction Following Liver Transplant. JAMA Surg. Published online February 11, 2026. doi:10.1001/jamasurg.2025.6539
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