Key Points:
Hepatorenal syndrome type 1 (HRS-1) is an often fatal, but potentially reversible, kidney failure in patients with decompensated cirrhosis.
Treatment with terlipressin in patients with HRS-1 is associated with a reduction in the need for RRT.
Background: Hepatorenal syndrome type 1 (HRS-1)—also known as hepatorenal syndrome-AKI (HRS-AKI)—is a rapidly progressing and usually fatal, but potentially reversible, kidney failure occurring in patients with decompensated cirrhosis. A large proportion of patients with HRS-1 require renal replacement therapy (RRT). Terlipressin demonstrated efficacy in reversing HRS and improving renal function in patients with HRS-1 in three phase III, randomized, clinical trials (RCTs; i.e., OT-0401, REVERSE, and CONFIRM). However, these RCTs were not designed to evaluate the effect of terlipressin on the requirement of RRT. In this study, the effect of terlipressin on RRT requirements in the pooled phase III patient population was assessed.
Methods: For this retrospective analysis, data from patients who participated in the OT-0401, REVERSE, and CONFIRM studies were integrated in the largest-to-date randomized database (N=608).
Results: The need for RRT was significantly decreased in patients in the terlipressin group versus the placebo group by day 30 (28.1% versus 35.9%, respectively; P = 0.040) and day 60 (30.1% versus 37.9%, respectively; P = 0.045) in the pooled population and also postliver transplantation (LT) at day 60 (20.5% versus 40.3%, respectively; P = 0.008) and day 90 (25.3% versus 43.1%, respectively; P = 0.018). More patients were alive and RRT-free by day 90 in the overall population (36.9% versus 28.5%; P = 0.030) and among patients who received an LT (60.0% versus 39.7%; P = 0.010). Random assignment to receive terlipressin was an independent positive predictor of avoidance of RRT (P = 0.042); while higher baseline serum creatinine (sCr) level and Child-Pugh scores were negatively associated with RRT avoidance (P < 0.001 and P = 0.040, respectively).
Conclusions: Terlipressin decreased the requirement of RRT compared with placebo among patients with HRS-1, including those receiving LT. A lower sCr level at the beginning of therapy was associated with avoidance of RRT.
Trial registration: ClinicalTrials.gov NCT00089570 NCT01143246 NCT02770716.