What is the treatment for Hepatorenal (HRS) syndrome?

Treatment of Hepatorenal Syndrome

The first-line treatment for hepatorenal syndrome (HRS) is to stop diuretics, administer albumin, and use vasoconstrictors, with terlipressin plus albumin being the most effective option. 1

Initial Management

• Stop diuretics immediately upon diagnosis of acute kidney injury (AKI) 2
• Consider withholding non-selective beta-blockers (NSBBs), particularly in hypotensive patients 2

First-Line Pharmacological Treatment

Terlipressin + Albumin (Preferred)

• Dosing regimen:

  • Terlipressin: Initial dose 1 mg IV every 4-6 hours
  • Can be increased stepwise up to 2 mg every 4-6 hours (maximum 12 mg/day) if serum creatinine decreases <25% after 2 days 1
  • Alternative administration: Continuous IV infusion (starting at 2 mg/day, increased every 24-48 hours up to 12 mg/day) may reduce ischemic side effects 2
  • Continue until serum creatinine returns to baseline or for maximum 14 days 2, 1

• Albumin administration:

  • Day 1: 1-1.5 g/kg body weight
  • Subsequent days: 40-50 g/day or 1 g/kg on day 3 2, 1

• Efficacy:

  • Response rate of approximately 29-70% (average ~50%) 2, 1, 3
  • FDA-approved based on the CONFIRM trial showing significantly higher rates of HRS reversal compared to placebo (29.1% vs 15.8%) 4

Alternative Options (When Terlipressin Unavailable)

Norepinephrine + Albumin

• Dosing: 0.5-3 mg/hour continuous IV infusion 1
• Setting: Requires ICU and central venous access
• Efficacy: Similar efficacy to terlipressin but fewer supporting data 2, 1
• Target: Increase mean arterial pressure by at least 10 mmHg or increase urine output >200 mL/4 hours 2

Midodrine + Octreotide + Albumin

• Dosing:
  • Midodrine: Up to 12.5 mg orally three times daily
  • Octreotide: 200 μg subcutaneously three times daily
  • Albumin: 10-20 g/day IV for up to 20 days 1
• Efficacy: Significantly less effective than terlipressin (28.6% vs 70.4% response rate) 3

Monitoring During Treatment

• Daily assessment of:
  • Serum creatinine
  • Blood pressure
  • Heart rate
  • Urine output
  • Signs of ischemic complications (abdominal pain, digital ischemia) 1

Treatment Duration and Response Assessment

• Continue treatment until serum creatinine decreases below 1.5 mg/dL or for maximum 14 days 1
• If creatinine remains at or above pretreatment level over 4 days with maximum tolerated doses, consider discontinuing therapy 2

Advanced Treatment Options

• Transjugular Intrahepatic Portosystemic Shunt (TIPS):

  • Consider in selected patients with partial response to medical therapy 1
  • Not recommended as first-line for HRS-AKI due to insufficient data 2
  • Contraindicated in severe liver failure or significant encephalopathy 1

• Renal Replacement Therapy (RRT):

  • Consider as bridge to liver transplantation in non-responders to vasoconstrictors 1
  • Indications: Severe electrolyte/acid-base disturbances, volume overload, or uremia 1
  • Continuous RRT is preferred 2

• Liver Transplantation:

  • Definitive treatment for HRS 1, 5, 6
  • Expedited referral should be considered for all patients with cirrhosis, ascites, and HRS 1

Important Clinical Considerations

• Despite treatment, prognosis remains poor without liver transplantation, with median survival of approximately 3 months 1
• Early diagnosis and treatment are critical for improving outcomes 1
• Higher baseline serum creatinine predicts poorer response to vasoconstrictors 1
• Monitor closely for adverse effects of vasoconstrictors, particularly ischemic complications 1