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 (1 g/kg on day 1, then 20-40 g/day) being the first-line treatment, as supported by the most recent and highest quality study 1. The treatment of HRS involves several key components, including:
- Vasoconstrictors, such as terlipressin or norepinephrine, to improve kidney function
- Albumin infusion to optimize volume status and improve effective arterial blood volume
- Identification and treatment of underlying precipitating factors, such as infections or gastrointestinal bleeding
- Discontinuation of nephrotoxic medications The use of terlipressin, in combination with albumin, has been shown to be effective in improving kidney function and short-term survival in patients with HRS-AKI, with a response rate of 20%-80% (average ~50%) 1. If terlipressin is unavailable, norepinephrine (0.5-3 mg/hour continuous IV infusion) with albumin is an effective alternative, although there are fewer data to support its use 1. For patients who cannot access either terlipressin or norepinephrine, 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, although it is less effective 1. Liver transplantation remains the definitive treatment for eligible patients with HRS, as it addresses the underlying liver dysfunction that drives the pathophysiology of this condition 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, 6
- Norepinephrine and vasopressin as acceptable alternatives in countries where terlipressin is not available 3
- Midodrine plus octreotide, which appears to be an effective pharmacologic regimen for patients with Type II HRS 3, 4, 7
- Non-pharmacologic options include:
Liver Transplantation
Liver transplantation is considered the best available treatment for HRS and the preferred definitive treatment option 3, 4, 5. It offers a clear survival benefit to patients with HRS regardless of prior therapy with vasoconstrictors 5.
Comparison of Treatment Options
A randomized 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 is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS 6. Another study found that combination treatment with octreotide, midodrine, and albumin improves survival in patients with type 1 and type 2 HRS 7.