What is the treatment for hepatorenal syndrome?

From the Guidelines

The treatment for hepatorenal syndrome (HRS) should involve terlipressin (1 mg/4–6 h intravenous bolus) in combination with albumin as the first-line therapeutic agent, with the aim of improving renal function sufficiently to decrease serum creatinine to less than 133 lmol/L (1.5 mg/dl). This approach is based on the most recent and highest quality evidence available, including a study published in 2022 1, which suggests that vasoconstrictors, such as terlipressin, are the mainstay of pharmacological treatment for HRS.

Key Considerations

• The dose of terlipressin should be increased in a stepwise manner up to a maximum of 2 mg/4 h if serum creatinine does not decrease at least 25% after 3 days, as recommended by the EASL clinical practice guidelines 1.
• Treatment should be discontinued within 14 days if there is no response or only a partial response, as indicated by a lack of decrease in serum creatinine to less than 133 lmol/L 1.
• Albumin infusion is crucial in expanding plasma volume and improving cardiac output, and its administration should be considered alongside vasoconstrictor therapy 1.
• Norepinephrine (0.5-3 mg/hour) with albumin or midodrine (7.5-12.5 mg orally three times daily) plus octreotide (100-200 mcg subcutaneously three times daily) with albumin are alternatives in countries where terlipressin is unavailable, as suggested by various studies 1.

Additional Recommendations

• Patients should have all nephrotoxic medications discontinued, including NSAIDs and diuretics, to prevent further renal injury.
• Volume status should be optimized, and infections treated aggressively if present, to address potential underlying causes of HRS.
• Liver transplantation remains the definitive treatment for eligible patients, as it addresses the underlying liver disease causing the circulatory dysfunction, and should be considered for patients with HRS, especially those with type 1 HRS, which is particularly severe with rapid deterioration of kidney function 1.

From the FDA Drug Label

TERLIVAZ is a vasopressin receptor agonist indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function. The treatment for hepatorenal syndrome is terlipressin (IV), a vasopressin receptor agonist, which is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function 2. Key points:

• 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) 2.
• Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit from terlipressin 2.

From the Research

Treatment Options for Hepatorenal Syndrome

The treatment for hepatorenal syndrome (HRS) includes:

• Liver transplantation, which is considered the best treatment option for HRS 3, 4, 5, 6
• Vasoconstrictor drugs, such as terlipressin, which are effective in managing HRS 3, 4, 7, 5, 6
• Albumin, which is often used in combination with vasoconstrictors to improve renal function 3, 4, 7, 5, 6
• Midodrine and octreotide, which can be used as an alternative treatment for HRS when terlipressin is not available 7
• Transjugular intrahepatic portosystemic shunt (TIPS), which can improve renal function by reducing portal pressure and decreasing sympathetic drive associated with portal hypertension 5

Efficacy of Treatment Options

• Terlipressin plus albumin has been shown to be more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS 7
• The combination of terlipressin and albumin has been demonstrated to be efficacious in the reversal of HRS and is used worldwide 6
• Liver transplantation offers a clear survival benefit to patients with HRS, regardless of prior therapy with vasoconstrictors 3

Importance of Early Diagnosis and Treatment

• Early diagnosis of HRS is central to its management, and recent changes in the definition of HRS help identify patients at an earlier stage 4
• Prompt treatment of HRS is crucial to improve patient outcomes, and liver transplantation should be considered as soon as possible for suitable candidates 3, 4, 5, 6