What are the treatment options for Hepatorenal Syndrome (HRS)?

From the Guidelines

Hepatorenal syndrome (HRS) treatment requires prompt intervention with vasoconstrictors combined with albumin as the cornerstone therapy, with terlipressin (0.5-2 mg IV every 4-6 hours) plus albumin (20-40g/day IV) being the first-line treatment, as supported by the most recent and highest quality study 1. The treatment of HRS involves the use of vasoconstrictors, such as terlipressin or norepinephrine, in combination with albumin to improve kidney function.

• The first-line treatment is terlipressin (0.5-2 mg IV every 4-6 hours) plus albumin (20-40g/day IV), continued until serum creatinine improves or for up to 14 days.
• If terlipressin is unavailable, norepinephrine (0.5-3 mg/hour continuous IV infusion) with albumin is an alternative.
• For patients who cannot access either, the combination of midodrine (7.5-12.5 mg orally three times daily) and octreotide (100-200 mcg subcutaneously three times daily) with albumin can be used, though it's less effective. The administration of albumin helps expand plasma volume and improve cardiac output, which is essential for improving renal perfusion in patients with HRS. Patients should receive supportive care, including:
• Careful fluid management
• Avoidance of nephrotoxic drugs
• Treatment of precipitating factors like infections or gastrointestinal bleeding Renal replacement therapy may be needed as a bridge to liver transplantation, which remains the definitive treatment for HRS. These interventions work by counteracting the splanchnic vasodilation and renal vasoconstriction that characterize HRS, improving effective arterial blood volume and renal perfusion, as noted in 1.

From the FDA Drug Label

The efficacy of TERLIVAZ was assessed in a multicenter, double-blind, randomized, placebo-controlled study (CONFIRM) (NCT02770716). Patients with cirrhosis, ascites, and a diagnosis of HRS-1 with a rapidly progressive worsening in renal function to a serum creatinine (SCr) ≥2. 25 mg/dL and meeting a trajectory for SCr to double over two weeks, and without sustained improvement in renal function (<20% decrease in SCr and SCr ≥2. 25 mg/dL) 48 hours after both diuretic withdrawal and the beginning of plasma volume expansion with albumin were eligible to participate.

Patients were randomized 2:1 to treatment with TERLIVAZ (N=199) or placebo (N=101). Patients received 1 mg terlipressin acetate (equivalent to TERLIVAZ 0. 85 mg) or placebo every 6 hours administered as an IV bolus injection over 2 minutes for a maximum of 14 days.

The treatment options for Hepatorenal Syndrome (HRS) include:

• Terlipressin: a vasopressin receptor agonist that can increase renal blood flow in patients with HRS by reducing portal hypertension and blood circulation in portal vessels and increasing effective arterial volume and mean arterial pressure (MAP) 2.
• Albumin therapy: used in conjunction with terlipressin to help improve renal function 2.
• Plasma volume expansion: used to help improve renal function 2.
• Diuretic withdrawal: used to help improve renal function 2.

From the Research

Treatment Options for Hepatorenal Syndrome (HRS)

The treatment options for HRS can be categorized into pharmacologic and non-pharmacologic therapies.

• Pharmacologic therapies include:
  • Terlipressin with albumin volume expansion, which is the preferred pharmacologic therapy for the treatment of patients with HRS 3, 4, 5
  • Norepinephrine and vasopressin as acceptable alternatives in countries where terlipressin is not available 3
  • Midodrine plus octreotide for patients with Type II HRS, which can be administered outside of an intensive care unit setting 3, 4, 6
• Non-pharmacologic options include:
  • Artificial hepatic support devices 3, 4
  • Renal replacement therapy 3
  • Transjugular intrahepatic portosystemic shunt (TIPS) 3, 4, 6
  • Molecular adsorbent recirculating system (MARS), an albumin-based dialysis system 4
  • Liver transplantation, which is the preferred definitive treatment option for HRS 3, 4, 7

Efficacy of Treatment Options

Studies have shown that terlipressin plus albumin is effective in improving renal function in patients with HRS 5.

• The combination of octreotide, midodrine, and albumin has also been shown to improve survival and renal function in patients with HRS type 1 and type 2 6.
• Long-term treatment with terlipressin and albumin may be an option for selected patients with recurrent HRS awaiting liver transplantation 7.

Considerations for Treatment

Careful monitoring is needed to ensure tissue ischemia and severe adverse effects do not occur with vasoconstrictor therapy 3.

• The role of other therapies is predominantly to prolong survival sufficiently to allow patients to undergo transplantation 3.
• The exact role of TIPS in HRS needs further evaluation, as patients with HRS are particularly at risk for complications such as encephalopathy and liver failure 4.