Vasoconstrictor Therapy for Hepatorenal Syndrome in Liver Cirrhosis

Abstract

Hepatorenal syndrome is a severe, but not uncommon complication of decompensated liver cirrhosis. In particular, the rapidly progressive form of hepatorenal syndrome (type 1) is associated with a dismal prognosis. Established hepatorenal syndrome has a spontaneous reversibility below 5%. Hepatorenal syndrome is involved in more than 50% of cirrhosis-related mortality. Thus, any treatment capable of reversing hepatorenal syndrome would be expected to reduce morbidity and mortality from liver cirrhosis. A pathophysiological hallmark of hepatorenal syndrome is arterial underfilling due to an extreme splanchnic vasodilatation. Consequently, potent vasoconstrictors capable of reversing this vasodilatation have been investigated in hepatorenal syndrome. Several vasoconstrictors including the alpha-adrenergic agonists, midodrine and noradrenalin, and the vasopressor analogues, ornipressin and terlipressin, have all been associated with a significant improvement in renal function in 57 to 100% of cases and even reversal of hepatorenal syndrome in 42 to 100% of cases. The majority of recent studies are on terlipressin. A randomized, controlled trial showed a significant effect of terlipressin on reversal of hepatorenal syndrome. The contribution of volume expansion to the beneficial effects of vasoconstrictors on hepatorenal syndrome remains to be determined. In general, reversal of hepatorenal syndrome was associated with an improved survival. However, it remains to be determined if vasoconstrictor therapy should be used in hepatorenal syndrome in general, or if it should be reserved for potential candidates for liver transplantation. In conclusion, evidence for a beneficial effect of vasoconstrictor therapy for the treatment of hepatorenal syndrome is steadily accumulating. Confirmation of the preliminary data in larger randomized, controlled trials looking at long-term survival is required.

Frequency of Hepatorenal Syndrome Among Patients With Cirrhosis and Outcome After Treatment

“…Research has proved that the vasoconstrictor agents affecting the splanchnic circulation are more effective that the vasodilator medication for renal circulation. Promising results have been reported after control trials with vasoconstrictor agents such as agonists of vasopressin V1 receptor, such as ornipressin and terlipressin, and somatostatin analogue, such as octreotide [ 23 ].…”

Kidney injury in cirrhosis: pathophysiological and therapeutic aspects of hepatorenal syndromes

“…Renal blood flow (RBF) decreases with the advancement of renal vasoconstriction and the clinical stage . Data originally published by Ring‐Larsen H. in Scand J Clin Lab Invest 1977.…”

“…Because of this, even minor reductions in arterial blood pressure may be harmful to renal perfusion and function and in these patients, low arterial pressure relates to survival . Figure illustrates how the RBF decreases with the advancement of the clinical stage of liver dysfunction .…”

“…Specific treatment of the HRS includes administration of vasoconstrictors such as terlipressin in combination with infusion of human albumin, also with revised HRS criteria including infection as a precipitating event . A recent meta‐analysis has shown that this treatment improves kidney function and reverses HRS type 1 . Terlipressin does not seem to have a sustained effect in patients with HRS type 2.…”

A prospective study to compare the efficacy of noradrenaline verses terlipressin in hepatorenal syndrome in patients with advanced cirrhosis

“…9 Midodrine, an orally administered α1-adrenergic agonist, and octreotide, a somatostatin analogue that inhibits endogenous vasodilators, have been used in combination with albumin for type 1 HRS. 10,11 A head-to-head randomized controlled study has been performed between terlipressin with albumin and midodrine plus octreotide and albumin. The group receiving terlipressin had a significantly higher rate of recovery of renal function in comparison to the group receiving midodrine and octreotide.…”