Efficacy of Early Terlipressin Plus Albumin Therapy in Comparison to Standard Treatment for HRS-AKI in Acute-on-chronic Liver Failure- A Randomized Open Label Study.

Acute on chronic liver failure (ACLF) is a distinct entity where, because of severe acute hepatic injury, a rapid loss of liver function develops in a patient with previous chronic liver disease(4). These patients have severe hepatic dysfunction, and outcome is defined by functional hepatic reserve and extent of extra-hepatic organ failures(5). Renal failure is a frequent extra-hepatic organ failure, and its presence is an independent prognostic marker for mortality(12). The pathophysiological basis of renal dysfunction in patients with ACLF is different compared to those with decompensated cirrhosis (DC)(6). Systemic inflammation is the hallmark of ACLF, characterized by a cytokine storm wherein there is an increase in both pro- and anti-inflammatory cytokines, such as interleukin (IL)-6, IL-8, IL-1β, and IL-10, leading to circulatory dysfunction and organ failure(3). These patients therefore have a higher incidence and progression of acute kidney injury (AKI). Diagnosis of HRS-AKI in ACLF currently requires 48 h of volume repletion with albumin and diuretic withdrawal. Therefore waiting for 48 hours to start treatment with terlipressin can be associated with worsening of AKI stage, worsening of ACLF stage and thereby suboptimal treatment response and high mortality despite treatment response. Therefore early initiation of terlipressin as continuous infusion after volume repletion with IV albumin in ACLF-AKI is safe and prevents AKI progression by splanchnic vasoconstriction and improved renal perfusion.