The chemokine CXCL14 is a novel early prognostic biomarker for poor outcome in acetaminophen-induced acute liver failure

Abstract

Background and Aims: Patients with acetaminophen-induced acute liver failure (APAP-ALF) are more likely to die while on the liver transplant waiting list than those with other causes of ALF. Therefore, there is an urgent need for prognostic biomarkers that can predict the need for liver transplantation early after an APAP overdose. Approach and Results: We evaluated the prognostic potential of plasma chemokine CXCL14 concentrations in APAP overdose patients (n=50) and found CXCL14 is significantly higher in non-surviving patients compared to survivors with ALF (p<0.001). Logistic regression and AUROC analyses revealed that CXCL14 outperformed the MELD score better discriminating between non-survivors and survivors. We validated these data in a separate cohort of samples obtained from the Acute Liver Failure Study Group (n=80), where MELD and CXCL14 had similar AUC (0.778), but CXCL14 demonstrated higher specificity (81.2 vs. 52.6) and positive predictive value (82.4 vs. 65.4) for death or need for liver transplantation. Next, combining the patient cohorts and using a machine learning training/testing scheme to mimic the clinic scenario, we found that CXCL14 outperformed MELD based on AUC (0.821 vs. 0.787), however combining MELD and CXCL14 yielded the best AUC (0.860). Conclusions: We find in two independent cohorts of APAP overdose patients that circulating CXCL14 concentration is a novel early prognostic biomarker for poor outcome which may aid in guiding decisions regarding patient management. Moreover, our findings reveal that CXCL14 performs best when measured soon after patient presentation to the clinic, highlighting its importance for early warning of poor prognosis.