Efficacy and safety of terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome

Abstract

Terlipressin is an analog of the natural hormone arginine-vasopressin. It is used in the treatment of patients with cirrhosis and bleeding esophageal varices (BEV) and in patients with hepatorenal syndrome (HRS): two of the most dramatic and feared complications of cirrhosis. Terlipressin exerts its main pharmacological effect through stimulation of vasopressin-1 receptors. These receptors are located in vascular smooth muscle and mediate vasoconstriction. In patients with cirrhosis and portal hypertension, treatment with terlipressin increases mean arterial pressure and decreases portal flow and pressure within minutes of administration. Furthermore, in patients with ascites terlipressin improves glomerular filtration and excretion of sodium. Terlipressin decreases failure of initial hemostasis by 34%, decreases mortality by 34%, and is considered a first-line treatment for BEV, when available. Terlipressin in combination with albumin reverses type 1 HRS in 33%-60% of cases and is the only treatment with proven efficacy in randomized trials. The safety profile is favorable when considering the clinical efficacy and the high mortality of these clinical entities. Adverse events are mostly cardiovascular and related to vasoconstriction. Mortality and withdrawal of terlipressin due to adverse events occurs in less than 1% of cases. Mild adverse events related to terlipressin treatment occur in 10%-20% of patients. The benefit, however, of terlipressin on long-term survival in HRS remains to be determined. At present, treatment with terlipressin and albumin is considered the most efficient therapy and should therefore be recommended for the treatment of type 1 HRS-1.