Identification and Internal Validation of a Novel Pre-Transplant Biomarker Panel to Predict Mortality Following Liver Transplantation: The Liver Immune Frailty Index

Panayotova, Guergana G.; Simonishvili, Sopio; Nguyen, Duc T.; Graviss, Edward A.; Aware, Nikita; Manner, Carl J.; Minze, Laurie J.; Ayorinde, Tumininu; Qin, Yong; Jin, Lianhua; Moore, Linda W.; Paterno, Flavio; Saharia, Ashish; Mobley, Constance M.; Amin, Arpit; Hobeika, Mark J.; Pyrsopoulos, Nikolaos; Li, Xian Chang; Guarrera, James V.; Ghobrial, R. Mark; Lunsford, Keri E.

doi:10.21203/rs.3.rs-2134172/v2

Cited by 1 publication

(6 citation statements)

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“…We have previously described the Liver Immune Frailty Index (LIFI), a biomarker panel based on HCV IgG status and plasma levels of MMP-3 and Fractalkine, which quanti es pre-LT immune dysfunction (a.k.a., immune frailty) and predicts risk of post-LT futility (23). Whether this model outperforms other conventional clinical scoring models was not known.…”

Section: Discussionmentioning

confidence: 99%

“…The LIFI score was calculated as previously described (23). LIFI was compared to currently accepted medical acuity scoring systems suggested for the liver transplant population.…”

Section: Score Model Calculationsmentioning

confidence: 99%

“…On internal validation, LIFI predicts futility with a C-statistic=0.84, which exceeds predictive capacity of previously described models. Speci cally, LIFI-high LT recipients had a 58.3% risk of 1-year mortality post-LT compared to 12.7% for LIFI-moderate and 1.4% for LIFI-low (23).…”

Section: Introductionmentioning

confidence: 98%

“…Objective parameters to accurately stratify patients' risk of post-LT death prior to LT are lacking. This, in conjunction with increasing recipient severity of illness at the time of transplant (17,(20)(21)(22)(23), risks futile LT. There is a critical need to accurately stratify LT candidates' risk of post-LT mortality prior to LT to optimize patient selection and avoid futility.…”

Section: Introductionmentioning

confidence: 99%

“…Transplant candidate immune dysfunction appears to be a critical component of overall patient severity of illness and susceptibility to complications. Cirrhosis ultimately leads to profound metabolic and immunologic dysfunction (24,25), resulting in both physical and immunologic frailty (23). Despite a clear association with post-transplant outcomes, immune dysfunction is not currently utilized in pre-LT candidate assessment.…”

Section: Introductionmentioning

confidence: 99%

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

Medina-Morales

Panayotova

Nguyen

et al. 2023

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

“…The LIFI score was calculated as previously described (23). LIFI was compared to currently accepted medical acuity scoring systems suggested for the liver transplant population.…”

Section: Score Model Calculationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%