*Purpose: Infection and sepsis are the greatest contributors to early post-liver transplant (LT) mortality. These often result from ongoing immune dysfunction, or “Immune Frailty”. We have previously explored pre-LT biomarkers predicting post-LT mortality, the Liver Immune Frailty Index (LIFI). This study expands initial observations and performs internal validation of LIFI to predict post-LT mortality.

*Methods: Plasma from 262 LT recipients was analyzed on POD-0 via Luminex. Clinical data was correlated with 24 chemokines/cytokines (sIL6rβ, GCP-2, CCL1, SDF, MMP2, TNF-α, BAFF, Eotaxin, MMP3, IP-10, IL-10, CTACK, Fractalkine, GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL7, IL-8, IL-12, IL-13).

*Results: Cox-proportional hazard clinically correlated pre-LT sIL6rβ, MMP2, BAFF, Eotaxin, MMP3, Fractalkine, IL-1β, and IL-2 elevation with 1yr post-LT mortality (p<0.05). Multivariate analysis identified HCV IgG, Eotaxin, and Factalkine as pre-LT predictors of 1yr post-LT mortality (c-statistic=0.86). LIFI was calculated by assigning weighted points proportional to covariate ß-coefficients multiplied by 10. LIFI-low, -moderate, and -high were categorized based on tertiles. Internal validation demonstrated a c-statistic=0.82 (Figure 1). LIFI-low recipients have a 2.9% 1yr mortality compared with 50% for LIFI-high (Figure 2).

*Conclusions: The LIFI score can predict post-LT mortality risk for a candidate immediately prior to LT. Immune Frailty likely directly relates to pre-LT alterations to the immune system, resulting from underlying cirrhosis and progressive sarcopenia. The inability to recover normal immune function after LT likely increases risk of infection, cancer recurrence, and ultimately death. The LIFI score may be a useful tool to augment patient assessment and stratification prior to LT.

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