What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

Terlipressin plus albumin is the first-line pharmacological treatment for type 1 hepatorenal syndrome (HRS-AKI), while liver transplantation remains the definitive treatment for both type 1 and type 2 HRS. 1, 2

Diagnostic Criteria

• HRS diagnosis requires cirrhosis with ascites, serum creatinine >1.5 mg/dL, no improvement after diuretic withdrawal and volume expansion with albumin, absence of shock, no recent nephrotoxic drug exposure, and absence of parenchymal kidney disease 1, 3
• A diagnostic paracentesis must be performed to rule out spontaneous bacterial peritonitis, which can precipitate HRS 4
• Two types are recognized:
  • Type 1 HRS (HRS-AKI): Rapidly progressive renal impairment with poor prognosis (median survival ~1 month if untreated) 3
  • Type 2 HRS: More stable renal impairment with better survival compared to Type 1 3

First-Line Treatment Options

• Terlipressin plus albumin:
  • Initial dose of 1 mg IV every 4-6 hours 1, 2
  • Increase stepwise to maximum 2 mg every 4 hours if serum creatinine doesn't decrease by at least 25% after 3 days 1
  • Continue until complete response or maximum 14 days for partial response 3
  • Limitation: Patients with serum creatinine >5 mg/dL are unlikely to benefit 2

Alternative Treatment Options (where terlipressin is unavailable)

• Midodrine plus octreotide plus albumin:

  • Midodrine: Titrate up to 12.5 mg orally three times daily 1, 4
  • Octreotide: 200 μg subcutaneously three times daily 1, 4
  • Albumin: 10-20 g IV daily for up to 20 days 1, 4
  • This regimen can be administered outside an ICU and even at home 4

• Norepinephrine plus albumin:

  • Requires ICU setting 1
  • Goal is to increase mean arterial pressure by 15 mmHg 1
  • Success rate of 83% reported in a pilot study 4

Definitive Treatment

• Liver transplantation:
  • Definitive treatment for both type 1 and type 2 HRS 1, 4
  • Expedited referral recommended for patients with type 1 HRS 1, 4
  • Post-transplant survival rates approximately 65% 1, 5
  • Treatment of HRS before transplantation (with vasoconstrictors) may improve post-transplant outcomes 1

Other Treatment Considerations

• Transjugular intrahepatic portosystemic shunt (TIPS):

  • Reported to be effective in type 1 HRS in an uncontrolled study of 7 patients 4, 1
  • Can improve renal function and control of ascites in patients with type 2 HRS 1
  • May be useful in maintaining patients who initially responded to pharmacological therapy 6

• Renal replacement therapy:

  • May be considered as a bridge to liver transplantation in selected patients with type 1 HRS 1
  • Useful in patients who don't respond to vasoconstrictor therapy and fulfill criteria for renal support 1

Prevention of HRS

• Albumin infusion with antibiotics when treating spontaneous bacterial peritonitis 5, 3
• Norfloxacin (400 mg/day) to reduce HRS incidence in advanced cirrhosis 1, 5
• Pentoxifylline (400 mg three times daily) to prevent HRS in severe alcoholic hepatitis 1, 5
• Avoiding nephrotoxic drugs in patients with advanced cirrhosis 3

Important Considerations and Pitfalls

• Despite improvements in survival with vasoconstrictors, long-term prognosis remains poor without liver transplantation 7, 6
• Recovery of renal function can be achieved in less than 50% of patients with HRS after terlipressin use 7
• The reduction in serum creatinine after treatment should not change the decision to perform liver transplantation since prognosis after recovering from HRS is still poor 1
• Differentiating HRS from acute tubular necrosis is challenging but important, as vasoconstrictors are not justified for treating ATN 8