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

From the Guidelines

The treatment for Hepatorenal Syndrome (HRS) should prioritize terlipressin (0.5-2mg IV every 4-6 hours) plus albumin (20-40g/day) as the first-line therapy, as it is the most effective regimen in improving renal function and reducing mortality, as supported by the most recent study 1. The goal of treatment is to address the underlying circulatory dysfunction and improve renal perfusion and function.

• Vasoconstrictors, such as terlipressin, are used to reverse splanchnic vasodilation, and albumin is used to expand plasma volume and improve cardiac output.
• The use of terlipressin has been shown to improve renal function in patients with HRS, with a response rate of 36-44% in randomized controlled trials 1.
• Norepinephrine (0.5-3 mg/hour) with albumin can be used as an alternative in countries where terlipressin is unavailable, or in patients with shock 1.
• Midodrine (7.5-12.5mg orally three times daily) plus octreotide (100-200mcg subcutaneously three times daily) with albumin can be used in non-ICU settings.
• Patients should have diuretics discontinued, nephrotoxic medications avoided, and be evaluated for liver transplantation, which is the definitive treatment 1.
• Continuous renal replacement therapy may be used as a bridge to transplant in severe cases, as recommended by the most recent guidelines 1. Key considerations in the management of HRS include:
• Monitoring for ischemic complications, such as arrhythmia, angina, and splanchnic and digital ischemia, in patients receiving terlipressin 1.
• Discontinuing terlipressin in patients who experience cardiac or ischemic symptoms, even if the symptoms have subsided following discontinuation of treatment 1.
• Evaluating patients for liver transplantation, which is the definitive treatment for HRS, and considering continuous renal replacement therapy as a bridge to transplant in severe cases 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. A total of 300 patients were enrolled; the median age was 55 years (range: 23 to 82), 60% were male, and 90% were White. At baseline, 40% had alcoholic hepatitis and 19% had ACLF Grade 3; the mean serum creatinine was 3. 5 mg/dL, and the mean MELD score was 33. Patients were randomized 2:1 to treatment with TERLIVAZ (N=199) or placebo (N=101). The primary efficacy endpoint was the incidence of Verified HRS Reversal, defined as the percentage of patients with 2 consecutive SCr values of ≤1. 5 mg/dL, obtained at least 2 hours apart while on treatment by Day 14 or discharge. A greater proportion of patients achieved Verified HRS Reversal in the TERLIVAZ arm compared to the placebo arm.

Treatment for HRS: Terlipressin (IV) is effective in treating Hepatorenal Syndrome (HRS) as shown in the CONFIRM study 2. The study demonstrated that a greater proportion of patients achieved Verified HRS Reversal with terlipressin compared to placebo.

• Key findings:
  • 29.1% of patients in the terlipressin arm achieved Verified HRS Reversal compared to 15.8% in the placebo arm.
  • The median age of patients was 55 years, and 60% were male.
  • Patients with alcoholic hepatitis and ACLF Grade 3 were included in the study.
• Mechanism of action: Terlipressin is a synthetic vasopressin analogue that increases renal blood flow in patients with HRS by reducing portal hypertension and increasing effective arterial volume and mean arterial pressure (MAP) 2.

From the Research

Treatment Options for Hepatorenal Syndrome (HRS)

• The mainstay of therapy for HRS is a vasoconstrictor (terlipressin or norepinephrine) combined with albumin, which achieves resolution of HRS in 40-50% of cases 3.
• Terlipressin plus albumin has been shown to improve renal function in almost 35-45% of patients with HRS, as well as to improve short-term survival in these patients 4.
• α-Adrenergic drugs, such as intravenous norepinephrine or oral midodrine plus subcutaneous octreotide, administered with albumin have also been used in the treatment of HRS, with promising results 4, 5, 6.

Comparison of Treatment Options

• A randomized controlled trial compared the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of HRS, and found that terlipressin plus albumin was significantly more effective in improving renal function in patients with HRS 5.
• Norepinephrine can be effectively used in a non-ICU setting as rescue therapy in patients who have not responded to midodrine and octreotide 6.

Other Treatment Approaches

• Transjugular intrahepatic portosystemic stent shunt (TIPS) has been shown to be an effective treatment for type 1 HRS in suitable patients with cirrhosis and ascites, following the improvement of renal function with combination therapy of midodrine, octreotide, and albumin 7.
• Liver transplantation is the only option for patients failing to respond to medical therapies 3.