Author information

• ¹Department of Nephrology, Ochsner Health, New Orleans, Louisiana, USA.
• ²Ochsner Clinical School, The University of Queensland, Brisbane, QLD, Australia.
• ³Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
• ⁴Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
• ⁵Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
• ⁶Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA.
• ⁷Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
• ⁸Department of Medicine, Baylor Scott & White All Saints Medical Center, Fort Worth, Texas, USA.
• ⁹Orphan Therapeutics LLC, Longboat Key, Florida, USA.
• ¹⁰Mallinckrodt Pharmaceuticals, Hampton, New Jersey, USA.

Abstract

Background: Hepatorenal syndrome type 1 (HRS-1)-also known as HRS-acute kidney injury (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 3 phase III, randomized clinical trials (RCTs; ie, OT-0401, REVERSE, and CONFIRM). However, these RCTs were not designed to evaluate the effect of terlipressin on the requirement of renal replacement therapy (RRT). Herein, the effect of terlipressin on RRT requirements in the pooled phase 3 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% vs 35.9%, respectively; P=0.040) and Day 60 (30.1% vs 37.9%, respectively; P=0.045) in the pooled population and also post-liver transplantation (LT) at Day 60 (20.5% vs 40.3%, respectively; P=0.008) and Day 90 (25.3% vs 43.1%, respectively; P=0.018). More patients were alive and RRT-free by Day 90 in the overall population (36.9% vs 28.5%; P=0.030) and among patients who received a LT (60.0% vs 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 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 serum creatinine level at the beginning of therapy was associated with avoidance of RRT.