What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

The first-line treatment for hepatorenal syndrome is vasoconstrictor therapy plus albumin, with terlipressin plus albumin being the most effective option for improving kidney function, while liver transplantation remains the only definitive curative treatment. 1, 2

Diagnosis and Classification

Before initiating treatment, proper diagnosis is essential:

• HRS is diagnosed when the following criteria are met:

  • Cirrhosis with ascites
  • Acute kidney injury (AKI)
  • No response after diuretic withdrawal and plasma volume expansion with albumin
  • Absence of shock
  • No current/recent use of nephrotoxic drugs
  • No signs of structural kidney injury 1

• HRS is classified into two types:

  • HRS-AKI (formerly Type 1): Rapid, progressive renal function impairment
  • HRS-CKD (formerly Type 2): Stable or slowly progressive renal impairment 1

Treatment Algorithm

First-Line Treatment: Vasoconstrictor Therapy + Albumin

1. Terlipressin + Albumin (preferred option):

   • Dosage: 0.85 mg IV every 6 hours
   • Albumin: 20-40 g/day
   • Continue until improvement in renal function or for up to 14 days
   • Note: Patients with serum creatinine >5 mg/dL are unlikely to benefit 1, 2

2. Alternative vasoconstrictors (if terlipressin unavailable):

   • Midodrine + Octreotide + Albumin

     • Midodrine: Titrate up to 12.5 mg orally three times daily
     • Octreotide: Target dose 200 μg subcutaneously three times daily
     • Albumin: 10-20 g/day IV for up to 20 days 3, 1

   • Norepinephrine + Albumin (requires ICU setting) 3, 1

Monitoring During Treatment

• Blood pressure and heart rate (terlipressin increases MAP by ~16 mmHg)
• Serum creatinine and urine output
• Monitor for adverse effects of vasoconstrictors (ischemic complications)
• Electrolyte balance 1, 2

Bridge Therapies

For patients awaiting liver transplantation or not responding to vasoconstrictors:

• Hemodialysis or continuous venovenous hemofiltration/hemodialysis
• Transjugular intrahepatic portosystemic shunt (TIPS) in selected patients 1, 4

Definitive Treatment

• Liver transplantation is the only curative treatment for HRS 3, 1
• Patients with cirrhosis, ascites, and type I HRS should have expedited referral for liver transplantation 3
• Consider simultaneous liver-kidney transplantation for patients with significant kidney damage 1

Efficacy and Outcomes

• Terlipressin has shown superior efficacy in reversing HRS compared to other treatments, with meta-analyses showing significant improvement over placebo 4
• Early treatment is critical - higher baseline serum creatinine predicts poorer response to vasoconstrictors 1
• Without liver transplantation, mortality remains high despite vasoconstrictor therapy 1, 5
• Long-term terlipressin and albumin therapy may be beneficial as a bridge to liver transplantation in patients with HRS recurrence 4

Important Considerations

• Differentiate HRS from acute tubular necrosis (ATN) as treatment approaches differ
• Bacterial infections, particularly spontaneous bacterial peritonitis, are major triggers of HRS and should be treated promptly
• Avoid nephrotoxic medications and large volume paracentesis without albumin administration
• Non-selective beta-blockers should be used with caution in patients with refractory ascites 1

The treatment of HRS has significantly improved with the advent of vasoconstrictor therapy, particularly terlipressin. However, the prognosis remains poor without liver transplantation, emphasizing the importance of early diagnosis, prompt initiation of treatment, and expedited evaluation for liver transplantation in suitable candidates.