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 should be performed to rule out spontaneous bacterial peritonitis, which can precipitate HRS 4, 1
• HRS is classified into two types:
  • Type 1 HRS (HRS-AKI): Rapidly progressive renal impairment with poor prognosis (median survival ~1 month if untreated) 3, 5
  • Type 2 HRS: More stable, chronic course with better survival compared to Type 1 3

Pharmacological Treatment Algorithm

First-Line Therapy

• Terlipressin plus albumin is the recommended first-line treatment for type 1 HRS 1, 3, 2
  • Initial dose: 1 mg IV every 4-6 hours
  • Increase dose 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
  • Limitation: Patients with serum creatinine >5 mg/dL are unlikely to benefit 2

Alternative Therapies (When Terlipressin Unavailable)

• Midodrine plus octreotide plus albumin 4, 1, 6
  • 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
• Norepinephrine plus albumin (requires ICU setting) 4, 1, 3
  • Goal: Increase mean arterial pressure by 15 mmHg

Definitive Treatment

• Liver transplantation is the definitive treatment for both type 1 and type 2 HRS 4, 1, 6, 3
• Patients with cirrhosis, ascites, and type 1 HRS should have expedited referral for liver transplantation 4, 1
• Post-transplant survival rates are approximately 65% in type 1 HRS 1, 6

Prevention of HRS

• Albumin infusion with antibiotics when treating spontaneous bacterial peritonitis 6, 3
• Norfloxacin (400 mg/day) to reduce HRS incidence in advanced cirrhosis 1, 6
• Pentoxifylline (400 mg three times daily) to prevent HRS in severe alcoholic hepatitis 1, 6
• Avoid nephrotoxic drugs in patients with advanced cirrhosis 3

Monitoring and Management

• Careful monitoring of urine output, fluid balance, arterial pressure, and vital signs is essential 6
• Patients with type 1 HRS are generally better managed in intensive or semi-intensive care units 6
• TIPS (transjugular intrahepatic portosystemic shunt) has been reported to be effective in type 1 HRS in small studies, but more evidence is needed 4, 1

Important Considerations and Pitfalls

• Differentiating HRS from acute tubular necrosis (ATN) is challenging but crucial, as vasoconstrictors are not indicated for ATN 5
• HRS and ATN may be considered as a continuum rather than distinct entities 5
• Despite improvements with vasoconstrictor therapy, mortality remains high without liver transplantation 7, 8
• Recovery of renal function may be achieved in less than 50% of patients with HRS after terlipressin use, and recovery may be partial even in full responders 7