What are the management strategies for Hepatorenal Syndrome (HRS)?

From the Guidelines

Management of hepatorenal syndrome (HRS) requires prompt intervention with vasoconstrictors combined with albumin infusion as the cornerstone of therapy, with terlipressin (0.5-2 mg IV every 4-6 hours) plus albumin (1 g/kg on day 1, then 20-40 g/day) being the first-line treatment, as recommended by the most recent and highest quality study 1.

Key Considerations

• The treatment should be continued for up to 14 days or until serum creatinine improves, with the goal of improving renal function and reducing mortality.
• If terlipressin is unavailable, norepinephrine (0.5-3 mg/hour) with albumin can be used as an alternative, as supported by studies 1.
• For patients who cannot access these medications, the combination of midodrine (7.5-12.5 mg orally three times daily) and octreotide (100-200 mcg subcutaneously three times daily) with albumin may be considered, though it's less effective, as noted in 1.

Supportive Care

• Careful fluid management is crucial to avoid volume overload and ensure adequate renal perfusion.
• Avoiding nephrotoxic drugs and treating infections promptly are essential to prevent further renal injury.
• Discontinuing diuretics is recommended to avoid exacerbating renal dysfunction.

Definitive Treatment

• Liver transplantation remains the definitive treatment for eligible patients with HRS, as it addresses the underlying liver dysfunction that triggers the pathophysiological cascade, as emphasized in 1.
• Early nephrology and hepatology consultation is essential, as dialysis may be needed as a bridge to transplantation in severe cases.

Additional Considerations

• Transjugular intrahepatic portosystemic shunt (TIPS) may be considered in patients with type 1 HRS who do not respond to vasoconstrictors, as suggested in 1.
• Renal replacement therapy (RRT) should be considered in non-responders to vasoconstrictors and in patients with end-stage kidney disease, as recommended in 1.

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 management of hepatorenal syndrome with terlipressin involves administering the drug to increase renal blood flow by:

• Reducing portal hypertension
• Reducing blood circulation in portal vessels
• Increasing effective arterial volume
• Increasing mean arterial pressure (MAP) 2 Key points:
• Terlipressin acts as a synthetic vasopressin analogue
• It has pharmacologic activity on its own and as a prodrug for lysine-vasopressin
• The drug increases diastolic, systolic, and mean arterial pressure, and decreases heart rate in patients with hepatorenal syndrome type 1 (HRS-1) 2

From the Research

Management of Hepatorenal Syndrome

The management of hepatorenal syndrome (HRS) involves a combination of vasoconstrictor agents and intravenous albumin, with the goal of improving renal function and reducing mortality rates.

• The use of terlipressin plus albumin has been shown to be effective in the reversal of HRS, with a significantly higher rate of recovery of renal function compared to midodrine and octreotide plus albumin 3.
• Midodrine and octreotide with albumin are used as an alternative treatment of HRS where terlipressin is not available, such as in the United States 3, 4.
• A standardized approach to HRS treatment using albumin, midodrine, and octreotide has been shown to improve treatment response rates and reduce the need for renal replacement therapy and liver transplantation 4.

Treatment Options

The following treatment options are available for HRS:

• Terlipressin plus albumin: This combination has been shown to be effective in improving renal function and reducing mortality rates 3, 5, 6.
• Midodrine and octreotide plus albumin: This combination is used as an alternative to terlipressin and has been shown to be effective in improving renal function, although to a lesser extent than terlipressin plus albumin 3, 4, 7.
• Transjugular intrahepatic portosystemic stent shunt (TIPS): This procedure has been shown to be effective in improving renal function in patients with type 1 HRS who have responded to medical therapy with midodrine, octreotide, and albumin 7.

Liver Transplantation

Liver transplantation is the definitive treatment for HRS, and patients with HRS should be prioritized on the waiting list for liver transplantation 5, 6.

• The Model for End-Stage Liver Disease (MELD) score, which includes creatinine as one of its main determinants, gives patients with HRS priority on the waiting list for liver transplantation 6.
• However, the MELD score may be reduced in responding patients, resulting in a longer waiting time for these patients than for non-responders, and the initial MELD score should be used to prioritize patients on the waiting list 6.