Acute-on-chronic liver failure (ACLF) is a complication of liver cirrhosis which is driven by dysfunctional innate immune activation and multiple organ failure. In ACLF, short-term mortality (28-day mortality) is ~50%. The risk of mortality in ACLF increases significantly with the occurrence of AKI. Hence, early detection and prevention of AKI is a priority for the management of ACLF patients. Here we show, that commonly used serum biomarkers of AKI i.e. FABP1, NGAL and Cystatin C, as well as a marker of inflammation IL-18, are not effective at discriminating between ACLF patients having AKI (ACLF-AKI) and ACLF patients without AKI (ACLF no-AKI). However, IL-18, which is a measure of inflammation, is able to predict mortality in ACLF patients and, Cystatin C is able to discriminate between ACLF-AKI and non-liver AKI. Our results demonstrate that the biomarkers of renal injury which might be effective in other etiologies of AKI may not be effective in early detection of ACLF associated AKI possibly suggesting a different pathomechanism of AKI in ACLF. We anticipate that this study will provide impetus to biomarker discovery studies towards early detection of AKI in ACLF patients.

Objective: Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis associated with high short-term mortality. The risk of mortality in ACLF increases with the occurrence of acute kidney injury (AKI). Hence, early detection of AKI is critical in ACLF. Serum biomarkers of tissue injury FABP1, IL-18, NGAL and CysC have been been reported to be associated with severity and mortality in ACLF in various reports. However, their performance in Indian ACLF population is unclear. Hence, the objective of our study was to evaluate the utility of these biomarkers in early detection of AKI and 28-day mortality in an Indian ACLF cohort. Results: Serum samples were collected from 150 study participants including ACLF, non-liver AKI and healthy controls. Biomarker levels were determined by ELISA. FABP1 and CysC levels were significantly different between ACLF patients with and without AKI however, none of the biomarkers were not significantly diagnostic for AKI nor predictive for 28-day mortality in our cohort. Therefore, in our cohort of ACLF patients, serum measurements of FABPI, NGAL and CysC and IL-18, do not have significant utility as predictors of AKI or 28-day mortality.