What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

The first-line treatment for hepatorenal syndrome is terlipressin plus albumin, which improves kidney function in 40-50% of patients and is associated with improved short-term survival. 1

Diagnosis Confirmation

Before initiating treatment, confirm the diagnosis by:

• Demonstrating increased serum creatinine (>1.5 mg/dL or 133 μmol/L)
• Excluding other causes of renal failure (hypovolemia, shock, parenchymal renal diseases, nephrotoxic drugs)
• Performing diagnostic paracentesis with SAAG calculation
• Obtaining abdominal and renal ultrasound to confirm cirrhosis and rule out obstructive uropathy 1

Initial Management Steps

1. Stop diuretics immediately
2. Consider withholding non-selective beta-blockers, particularly in hypotensive patients 1

Pharmacological Treatment Options

First-Line Therapy: Terlipressin + Albumin

• Dosing regimen:
  • Terlipressin: Start at 1 mg IV every 4-6 hours
  • Increase to maximum 2 mg every 4-6 hours if serum creatinine doesn't decrease by at least 25% after 3 days
  • Albumin: 1 g/kg on day 1, followed by 20-40 g/day 2, 1
• Duration: Continue until serum creatinine decreases below 1.5 mg/dL or for maximum 14 days 1
• Monitoring: Check serum creatinine daily and assess for cardiovascular complications
• Efficacy: Improves renal function in 40-50% of patients 2
• Limitation: Patients with serum creatinine >5 mg/dL are unlikely to benefit 3

Alternative Options (if terlipressin unavailable or contraindicated)

1. Norepinephrine + Albumin (ICU setting)

   • Administered as continuous infusion (0.5-3 mg/h)
   • Dose increased to achieve a raise in arterial pressure 2

2. Midodrine + Octreotide + Albumin

   • Midodrine: Start at 2.5-7.5 mg orally every 8 hours, titrate up to 12.5 mg three times daily
   • Octreotide: 100 μg subcutaneously every 8 hours, increase to 200 μg three times daily
   • Albumin: 10-20 g/day IV for up to 20 days 1
   • Can be administered outside the ICU and even at home 1

Response Predictors and Monitoring

• Favorable response predictors:

  • Serum bilirubin <10 mg/dL before treatment
  • Increase in mean arterial pressure >5 mm Hg at day 3 of treatment 2
  • Lower baseline serum creatinine (especially <5.0 mg/dL) 1, 3

• Median time to response: 14 days, shorter in patients with lower baseline serum creatinine 2

Non-Pharmacological Options

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

• May improve renal function in selected patients with partial response to medical therapy
• Limited applicability due to contraindications in many patients
• Contraindicated in severe liver failure or significant encephalopathy 2, 1

Renal Replacement Therapy

• Consider in patients who don't respond to vasoconstrictor therapy
• Useful as a bridge to liver transplantation
• Continuous renal replacement therapy preferred due to less hemodynamic instability 1

Liver Transplantation

• Only curative treatment for hepatorenal syndrome
• Expedited referral should be considered for all patients with cirrhosis, ascites, and HRS
• Consider simultaneous liver-kidney transplantation for patients with significant kidney damage 1, 4

Prevention of HRS

• Treatment of spontaneous bacterial peritonitis with albumin plus antibiotics reduces the risk of HRS development 1
• Norfloxacin (400 mg/day) has been shown to reduce the incidence of HRS in advanced cirrhosis 2
• Pentoxifylline (400 mg three times daily) may prevent HRS development in severe alcoholic hepatitis 2

Important Considerations

• Cardiovascular complications occur in approximately 12% of patients treated with terlipressin; most studies excluded patients with known severe cardiovascular conditions 2
• Recurrence after withdrawal of terlipressin therapy is uncommon, and retreatment is generally effective 2
• Despite treatment, prognosis remains poor without liver transplantation, with median survival of approximately 3 months for all HRS patients 1