Pre-transplant Biomarkers of Immune Dysfunction Improve Risk Assessment of Post-transplant Mortality Compared to Conventional Clinical Risk Scores

J Esli Medina-Morales; Guergana G Panayotova; Duc T Nguyen; Edward A Graviss; Gagan S Prakash; Jeffery A Marsh; Sopio Simonishvili; Yash Shah; Tumininu Ayorinde; Yong Qin; Lianhua Jin; Theofano Zoumpou; Laurie J Minze; Flavio Paterno; Arpit Amin; Grace Lee Riddle; R Mark Ghobrial; James V Guarrera; Keri E Lunsford

doi:10.21203/rs.3.rs-2548184/v1

Pre-transplant Biomarkers of Immune Dysfunction Improve Risk Assessment of Post-transplant Mortality Compared to Conventional Clinical Risk Scores

Res Sq [Preprint]. 2023 Feb 21:rs.3.rs-2548184. doi: 10.21203/rs.3.rs-2548184/v1.

Authors

J Esli Medina-Morales¹, Guergana G Panayotova¹, Duc T Nguyen², Edward A Graviss², Gagan S Prakash¹, Jeffery A Marsh¹, Sopio Simonishvili¹, Yash Shah¹, Tumininu Ayorinde¹, Yong Qin¹, Lianhua Jin¹, Theofano Zoumpou¹, Laurie J Minze¹, Flavio Paterno¹, Arpit Amin¹, Grace Lee Riddle¹, R Mark Ghobrial³, James V Guarrera¹, Keri E Lunsford¹

Affiliations

¹ Rutgers New Jersey Medical School.
² Houston Methodist Research Institute.
³ Houston Methodist Hospital.

Abstract

Introduction: There is a critical need to accurately stratify liver transplant (LT) candidates' risk of post-LT mortality prior to LT to optimize patient selection and avoid futility. Here, we compare previously described pre-LT clinical risk scores with the recently developed Liver Immune Frailty Index (LIFI) for prediction of post-LT mortality. LIFI measures immune dysregulation based on pre-LT plasma HCV IgG, MMP3 and Fractalkine. LIFI accurately predicts post-LT mortality, with LIFI-low corresponding to 1.4% 1-year post-LT mortality compared with 58.3% for LIFI-high (C-statistic=0.85).

Methods: LIFI was compared to MELD, MELD-Na, MELD 3.0, D-MELD, MELD-GRAIL, MELD-GRAIL-Na, UCLA-FRS, BAR, SOFT, P-SOFT, and LDRI scores on 289 LT recipients based on waitlist data at the time of LT. Survival, hazard of early post-LT death, and discrimination power (C-statistic) were assessed.

Results: LIFI showed superior discrimination (highest C-statistic) for post-LT mortality when compared to all other risk scores, irrespective of biologic MELD. On univariate analysis, the LIFI showed a significant correlation with mortality 6-months, as well as 1-, 3-, and 5-years. No other pre-LT scoring system significantly correlated with post-LT mortality. On bivariate adjusted analysis, African American race (p<0.05) and pre-LT cardiovascular disease (p=0.053) were associated with early- and long-term post-LT mortality. Patients who died within 1-yr following LT had a significantly higher incidence of infections, including 30-day and 90-day incidence of any infection, pneumonia, abdominal infections, and UTI (p<0.05).

Conclusions: LIFI, which measures pre-LT biomarkers of immune dysfunction, more accurately predicts risk of post-LT futility compared with current clinical predictive models. Pre-LT assessment of immune dysregulation may be critical in predicting mortality after LT and may optimize selection of candidates with lowest risk of futile outcomes.

Keywords: Cirrhosis; Clinical Risk Score; Liver Transplant; Liver Transplant Futility; Post-Transplant Mortality; Pre-Transplant Risk Assessment.

Publication types

Preprint