What is the treatment for hepatorenal syndrome?

Treatment for Hepatorenal Syndrome

Liver transplantation is the definitive treatment for hepatorenal syndrome, while terlipressin plus albumin is the first-line pharmacological treatment for bridging patients to transplantation or treating those who are not transplant candidates. 1

First-Line Pharmacological Treatment

• Terlipressin plus albumin is the reference treatment for hepatorenal syndrome, with high-strength evidence supporting its efficacy 2

  • Initial dose: 1 mg IV every 4-6 hours
  • Increase stepwise to maximum 2 mg every 4 hours if serum creatinine doesn't decrease by at least 25% after 3 days
  • Continue until complete response or maximum 14 days for partial response 1, 3
  • Albumin administration: 1 g/kg before initiating terlipressin, followed by 20-40 g/day 2

• FDA has approved terlipressin (TERLIVAZ) for improving kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function 4

  • Important limitation: Patients with serum creatinine >5 mg/dL are unlikely to experience benefit 4

Alternative Treatments

• Noradrenaline (norepinephrine) plus albumin is a reliable alternative to terlipressin in patients with central venous access 2

  • Requires ICU setting
  • Goal: Increase mean arterial pressure by 15 mmHg
  • Meta-analyses show no significant difference between terlipressin+albumin and noradrenaline+albumin in hepatorenal syndrome reversal or relapse rates 2
  • May have fewer adverse events per participant compared to terlipressin plus albumin (rate ratio 0.51,95% CrI 0.28 to 0.87) 5

• Midodrine plus octreotide plus albumin is recommended when terlipressin is unavailable 1

  • Midodrine: Titrate up to 12.5 mg orally three times daily
  • Octreotide: 200 μg subcutaneously three times daily
  • Albumin: 10-20 g IV daily for up to 20 days
  • Less effective than terlipressin or noradrenaline 2, 5

Definitive Treatment

• Liver transplantation is the definitive treatment for both type 1 and type 2 hepatorenal syndrome 1, 2, 3
  • Expedited referral for transplantation is recommended for patients with type 1 HRS
  • Post-transplant survival rates are approximately 65% in type 1 HRS 1, 3
  • Pharmacological treatments serve as a bridge to liver transplantation 6

Other Treatment Options

• Transjugular intrahepatic portosystemic shunts (TIPS) may improve renal function in type 2 HRS and selected patients with type 1 HRS 1, 2

  • Limited applicability due to contraindications in many patients with advanced liver disease 2

• Renal replacement therapy may be considered as a bridge to liver transplantation in selected patients with type 1 HRS 1

  • Limited data on artificial liver support systems 1

Prevention of Hepatorenal Syndrome

• Albumin infusion with antibiotics when treating spontaneous bacterial peritonitis 3, 7
• Norfloxacin (400 mg/day) can reduce HRS incidence in advanced cirrhosis 1, 3
• Pentoxifylline (400 mg three times daily) can prevent HRS development in patients with severe alcoholic hepatitis 1, 3
• Avoiding nephrotoxic drugs in patients with advanced cirrhosis 2, 3

Monitoring and Response Assessment

• Monitor serum creatinine, mean arterial pressure, urine output, and serum sodium concentration to assess response to therapy 2
• Response is characterized by progressive reduction in serum creatinine, increase in arterial pressure, urine volume, and serum sodium 2

Important Considerations and Pitfalls

• Diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis, which can precipitate HRS 1, 2
• Adverse effects of vasoconstrictors include cardiac or intestinal ischemia, pulmonary edema, and distal necrosis 2
• The reduction in serum creatinine levels after treatment and the related decrease in the MELD score should not change the decision to perform liver transplantation since the prognosis after recovering from HRS is still poor 1
• Differentiating hepatorenal syndrome from acute tubular necrosis is often challenging but important, as vasoconstrictors are not indicated for acute tubular necrosis 8