Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial.

Background and Aim:  Hepatorenal syndrome (HRS) occurs in about 18% of cirrhotic patients with ascites and is characterized by intense renal vasoconstriction, low glomerular filtration rate and preserved tubular function and normal renal histology. The aim of the present study was to examine the effects of terlipressin on renal function, systemic hemodynamics and clinical outcome in patients with HRS. Methods:  The study was a randomized controlled single-blind trial. We randomly assigned 24 consecutive patients with HRS to treatment with terlipressin 1 mg i.v. at 12-h intervals (group A; n = 12) or placebo at 12-h intervals (group B; n = 12). The end-point of the study was improvement in renal functions defined as reversal of HRS and survival at 15 days. Results:  The two groups were comparable at baseline. After treatment with terlipressin, urine output significantly (P < 0.05) increased progressively in group A (day 4, 960 ± 40 mL/24 h; day 8, 1068 ± 56 mL/24 h) compared with group B (day 4, 451 ± 40 mL/24 h; day 8, 291 ± 45 mL/24 h). Creatinine clearance improved (P < 0.05) in group A (day 4, 20.2 ± 2.1 mL/min; day 8, 35 ± 2.8 mL/min) compared with group B (day 4, 11.3 ± 1.3 mL/min; day 8, 9.3 ± 1.7 mL/min). Serum creatinine decreased in group A but not in group B (day 8, 1.6 ± 0.01 compared with 3.9 ± 0.26, P < 0.05). Mean arterial pressure increased significantly (P < 0.05) in group A. Terlipressin administration was associated with transient self-limiting side-effects including crampy abdominal pain in two patients and cardiac arrhythmias in three patients. Five of the 12 patients survived in group A compared with none in group B at day 15 (P < 0.05) and all survivors had reversal of HRS. Conclusion:  In patients with HRS, terlipressin significantly improved renal functions and systemic hemodynamics, and showed a trend towards better clinical outcome. The drug merits further evaluation with different dosages and longer schedules.