What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

The definitive treatment for hepatorenal syndrome (HRS) is liver transplantation, while terlipressin plus albumin is the first-line pharmacological treatment to bridge patients to transplantation or treat those who are not transplant candidates. 1, 2, 3

Diagnostic Criteria

• HRS diagnosis requires cirrhosis with ascites, acute kidney injury, 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
• Diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis, which can precipitate HRS 2

First-Line Pharmacological Treatment

• Terlipressin plus albumin is the first-line treatment for HRS-AKI (formerly Type 1 HRS) 1, 2, 3, 4
• Initial terlipressin dosing: 1 mg IV every 4-6 hours, with stepwise increase to maximum 2 mg every 4 hours if serum creatinine doesn't decrease by at least 25% after 3 days 1, 2
• Terlipressin increases renal blood flow by reducing portal hypertension and increasing mean arterial pressure 4
• Albumin is administered at 1 g/kg before initiating vasoconstrictor treatment, followed by 20-40 g/day 2
• Treatment should be continued until complete response or maximum 14 days for partial response 3
• Limitation: Patients with serum creatinine >5 mg/dL are unlikely to experience benefit from terlipressin 4

Alternative Pharmacological Treatments

• In regions where terlipressin is unavailable, midodrine plus octreotide plus albumin can be used 1, 2, 3
  • 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 is another alternative, requiring ICU setting, with goal to increase mean arterial pressure by 15 mmHg 1, 2
• Noradrenaline has shown similar efficacy to terlipressin in reversing HRS, with success rates of 83% 2

Definitive Treatment

• Liver transplantation is the only definitive treatment for both HRS-AKI and HRS-NAKI (formerly Type 1 and Type 2 HRS) 1, 2, 3
• Expedited referral for transplantation is recommended for patients with HRS-AKI 1
• Post-transplant survival rates are approximately 65% in HRS-AKI 1

Renal Replacement Therapy

• Continuous venovenous hemofiltration/hemodialysis may be considered as a bridge to liver transplantation in selected patients with HRS-AKI 1

Prevention of HRS

• Albumin infusion with antibiotics when treating spontaneous bacterial peritonitis 3
• Norfloxacin (400 mg/day) to reduce HRS incidence in advanced cirrhosis 1, 3
• Pentoxifylline (400 mg three times daily) to 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

• TIPS (transjugular intrahepatic portosystemic shunts) has limited evidence but may improve renal function in some patients 1, 2
• Adverse effects of vasoconstrictors include cardiac or intestinal ischemia, pulmonary edema, and distal necrosis 2
• Early diagnosis and prompt initiation of treatment are crucial for improving outcomes 5
• Differentiating HRS from acute tubular necrosis is challenging but important as vasoconstrictors are not indicated for ATN 6