AARC score and urine NGAL predict terlipressin non-response and mortality in patients with acute-on-chronic liver failure

Abstract

Background and aim: Acute-on-chronic liver failure (ACLF) patients with hepatorenal syndrome (HRS-AKI) have limited response to vasoconstrictors and worse outcomes, requiring biomarkers for early detection.

Methods: In a prospective cohort of ACLF patients (n = 240), urine NGAL was performed in patients with the clinical diagnosis of HRS-AKI, while in a subset of patients (n = 30), a complete panel of 17 urinary biomarkers was assessed for identifying terlipressin non-response (T-NR).

Results: ACLF patients with HRS-AKI, aged 45.84 ± 10.6 years, 91.2% males, 74.2% with alcohol etiology, mean urine NGAL of 1541.66 ± 1684.69 ng/ml, AARC score 10.19 ± 1.86, 155 (64.5%) had T-NR at day 4. T-NR was maximal for AARC grade 3 and was associated with a higher need of dialysis (50.3% vs 5.9%; OR 16.21, 6.23-42.19) and 28-day mortality (49.0% vs. 17.9%; HR 3.42, 1.96-5.95). AARC grade 3 (OR 38.21, 2.93-497.74), (HR 5.10, 1.19-21.84) and urine NGAL (OR 11.53, 5.66-23.49; AUROC 0.97, NGAL > 900 ng/ml) (HR 1.23, 1.02-1.49) were independent predictors of T-NR and 28-day mortality, respectively. It was interesting to observe a significant elevation in renal injury and a decrease in the repair markers in T-NR (p < 0.05).

Conclusion: Almost 60% of patients with ACLF and HRS-AKI experience non-response to terlipressin which predicts higher mortality and need for dialysis. High NGAL above 900 ng/ml predicts T-NR with 100% specificity for T-NR. ACLF patients with HRS, with AARC grade 3 and high NGAL have a high likelihood of T-NR and should be considered for alternative therapeutic modalities.

Keywords: AARC score; ACLF; AKI; Biomarker; Cholemic nephropathy; Dialysis; HRS; NGAL; RRT.