What is the role of terlipressin in Hepatorenal Syndrome (HRS)?

From the Guidelines

Terlipressin is the first-line treatment for hepatorenal syndrome (HRS), particularly HRS-AKI, as it effectively improves renal function and survival in patients with this condition, with a recommended dosing regimen of 1 mg intravenously every 6 hours, which can be increased to 2 mg every 6 hours if serum creatinine does not decrease by at least 25% after 3 days, alongside albumin administration to optimize volume status and enhance efficacy 1.

Key Points

• Terlipressin works by acting as a vasopressin analog that selectively constricts splanchnic blood vessels, reducing portal pressure and improving effective arterial blood volume and renal perfusion, addressing the pathophysiological mechanism of HRS, which involves splanchnic vasodilation and consequent renal vasoconstriction 2.
• Predictors of response to terlipressin treatment include markers of better liver function, such as a bilirubin of ≤ 10 mg/dL, better kidney function, as indicated by an sCr of ≤ 5 mg/dL, an increase in the MAP of ≥ 5 mm Hg with treatment, and lower grades of acute-on-chronic liver failure (ACLF) 2.
• Important precautions include monitoring for potential side effects, such as abdominal cramps, diarrhea, and more serious complications like ischemic events or respiratory failure, particularly in patients with cardiac or respiratory conditions, and exercising caution when administering terlipressin to patients with known cardiac failure or underlying respiratory conditions, especially those with baseline hypoxemia 2.
• The use of a continuous infusion of terlipressin has been shown to achieve the same efficacy as bolus dosing with a lower total daily dose and fewer side effects, and the need for continuation of albumin should be assessed carefully based on volume status, with point-of-care ultrasonography suggested as a potential method for assessment 1.

Administration and Monitoring

• Treatment with terlipressin should be initiated promptly upon diagnosis of HRS to maximize the chances of renal recovery, and should be continued for up to 14 days or until serum creatinine improves to below 1.5 mg/dL 3.
• Patients on terlipressin should be monitored for the development of ischemic complications, such as arrhythmia, angina, and splanchnic and digital ischemia, and terlipressin should not be resumed in patients who experience cardiac or ischemic symptoms, even if the symptoms have subsided following discontinuation of treatment 3.

From the FDA Drug Label

Terlipressin is thought to increase renal blood flow in patients with hepatorenal syndrome by reducing portal hypertension and blood circulation in portal vessels and increasing effective arterial volume and mean arterial pressure (MAP). The role of terlipressin in Hepatorenal Syndrome (HRS) is to:

• Increase renal blood flow
• Reduce portal hypertension
• Increase effective arterial volume and mean arterial pressure (MAP) 4

From the Research

Role of Terlipressin in Hepatorenal Syndrome (HRS)

• Terlipressin is a vasopressin analog that has been shown to be effective in the treatment of HRS, particularly when used in combination with albumin volume expansion 5, 6, 7, 8, 9.
• The mechanism of action of terlipressin in HRS involves increasing mean arterial pressure and systemic vascular resistance, while decreasing heart rate, cardiac output, and portal venous blood flow 7.
• Terlipressin has been shown to improve renal function and reduce mortality in patients with HRS, particularly those with type 1 HRS 6, 8, 9.
• Compared to other treatments, such as midodrine and octreotide, terlipressin has been shown to be more effective in improving renal function and reducing mortality 8.
• However, terlipressin may also be associated with adverse events, including cardiovascular and gastrointestinal symptoms 9.
• The use of terlipressin in HRS is considered a bridge to liver transplantation, and patients who respond to terlipressin and albumin may have an excellent post-transplantation outcome 7.

Comparison with Other Treatments

• Terlipressin has been compared to other treatments, such as norepinephrine, dopamine, and octreotide, and has been shown to have similar or superior efficacy in improving renal function and reducing mortality 6, 8.
• Midodrine and octreotide may be used as an alternative treatment for HRS in countries where terlipressin is not available 5, 8.
• The choice of treatment for HRS should be individualized and based on the patient's specific needs and circumstances 5.

Clinical Evidence

• The evidence for the use of terlipressin in HRS is based on several clinical trials, including randomized controlled trials and meta-analyses 6, 8, 9.
• The trials have shown that terlipressin is effective in improving renal function and reducing mortality in patients with HRS, particularly those with type 1 HRS 6, 8, 9.
• However, the evidence is not uniform, and some trials have reported conflicting results 6, 9.