What is the management for Hepatorenal Syndrome (HRS)?

From the Guidelines

The management of Hepatorenal Syndrome (HRS) should focus on improving renal function through vasoconstrictor therapy, specifically with terlipressin (0.5-2mg IV every 4-6 hours) combined with albumin (20-40g/day IV), as this approach has been shown to improve renal function and short-term survival in patients with HRS 1.

Key Considerations

• The treatment should be continued for 7-14 days until serum creatinine improves, with careful monitoring for side effects such as ischemic complications and respiratory failure 1.
• If terlipressin is unavailable, alternatives include norepinephrine (0.5-3 mg/hour continuous IV infusion) with albumin, or midodrine (7.5-12.5mg orally three times daily) plus octreotide (100-200mcg subcutaneously three times daily) with albumin 1.
• Volume status should be optimized with albumin infusion (1g/kg on day 1, followed by 20-40g/day), and diuretics and nephrotoxic medications should be discontinued 1.
• Infection screening with prophylactic antibiotics is essential as infections often trigger HRS, and continuous renal replacement therapy may be needed for severe cases with fluid overload, acidosis, or electrolyte disturbances 1.

Additional Recommendations

• Liver transplantation is the definitive treatment for eligible patients, as it addresses the underlying portal hypertension and liver dysfunction that cause the splanchnic vasodilation and renal vasoconstriction characteristic of HRS 1.
• The use of transjugular intra-hepatic portosystemic shunt (TIPS) may be considered in patients with HRS-1 and lower MELD scores, but its use should be limited to specific cases and under close monitoring 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. All patients underwent fluid challenge with intravenous albumin (1 g/kg on the first day (maximum 100 g) and 20 g/day to 40 g/day thereafter as clinically indicated). 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. On Day 4 of therapy, if SCr decreased by less than 30% from the baseline value, the dose was increased to 2 mg terlipressin acetate (equivalent to TERLIVAZ 1. 7 mg) every 6 hours.

The management for Hepatorenal Syndrome (HRS) includes:

• Fluid challenge with intravenous albumin
• Terlipressin administration, with an initial dose of 1 mg terlipressin acetate every 6 hours, which may be increased to 2 mg every 6 hours if serum creatinine (SCr) does not decrease by at least 30% from baseline by Day 4 of therapy 2
• Diuretic withdrawal and plasma volume expansion with albumin before initiating terlipressin therapy
• Monitoring of serum creatinine levels to assess response to therapy and adjust the dose as needed. Key points to consider in the management of HRS include:
• The use of terlipressin in combination with albumin infusion
• The importance of monitoring serum creatinine levels to assess response to therapy
• The potential need to adjust the dose of terlipressin based on the patient's response to therapy 2

From the Research

Management of Hepatorenal Syndrome (HRS)

The management of HRS typically involves a combination of pharmacological and supportive treatments.

• The definitive treatment of HRS is liver transplantation 3.
• When liver transplantation is not possible, HRS is treated with a combination of vasoconstrictor agents and intravenous albumin 3.
• Terlipressin, an analog of vasopressin, is likely to become the first-line standard of care for HRS 3.
• 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 4.
• Midodrine and octreotide with albumin are used as an alternative treatment of HRS, particularly in regions where terlipressin is not available 4.
• Norepinephrine plus albumin has been shown to be more effective than midodrine and octreotide plus albumin 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.

Treatment Options

• Terlipressin: initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there is no response 4.
• Midodrine: orally at an initial dose of 7.5 mg thrice daily, with the dose increased to a maximum of 12.5 mg thrice daily 4.
• Octreotide: subcutaneously, initial dose 100 μg thrice daily, and up to 200 μg thrice daily 4.
• Albumin: intravenously 1 g/kg of body weight on day 1 and 20-40 g/day thereafter 4.
• Norepinephrine: initially 0.5 mg/h, with the dose increased to a maximum of 3 mg/h 5.

Response to Treatment

• A complete response to treatment is defined as the return of serum creatinine to a value within 0.3 mg/dl of the baseline at the end of treatment 5.
• Age, bilirubin, and creatinine increase after diagnostic volume expansion are independent predictors of death in patients with HRS type 1 7.
• Survival is better in patients who respond to therapy, with a three-month survival rate of 19.7% in patients with HRS type 1 7.