What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

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

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 current/recent nephrotoxic drug exposure, and absence of parenchymal kidney disease 3
• Diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis, which can precipitate HRS 1
• Two types are recognized: Type 1 HRS (HRS-AKI) with rapid, progressive renal impairment, and Type 2 HRS with more stable kidney function 2

Pharmacological Treatment Algorithm

First-Line Therapy

• Terlipressin plus albumin is the first-line treatment for type 1 HRS 1, 3
  • Initial dose: 1 mg IV every 4-6 hours 1, 3
  • 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
  • Terlipressin increases renal blood flow by reducing portal hypertension and increasing effective arterial volume and mean arterial pressure 4
  • FDA approved for improving kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function 4
  • Note: Patients with serum creatinine >5 mg/dL are unlikely to experience benefit 4

Alternative Therapies

• In regions where terlipressin is unavailable, midodrine plus octreotide plus albumin is recommended 1, 3

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

• Norepinephrine plus albumin is another alternative 1, 3

  • Requires ICU setting 1
  • Goal: Increase mean arterial pressure by 15 mmHg 1
  • Success rate of 83% reported in a pilot study 1

Definitive Treatment

• Liver transplantation is the definitive treatment for both type 1 and type 2 HRS 1, 2, 3
• Expedited referral for transplantation is recommended for patients with type 1 HRS 1, 3
• Post-transplant survival rates are approximately 65% in type 1 HRS 1, 2
• Treatment of HRS before transplantation may improve post-transplant outcomes 1

Other Treatment Options

• Transjugular intrahepatic portosystemic shunt (TIPS) has shown improvement in renal function in type 2 HRS 1
• Renal replacement therapy may be considered as a bridge to liver transplantation in selected patients with type 1 HRS 1
• Continuous venovenous hemofiltration/hemodialysis may be used in patients who do not respond to vasoconstrictor therapy and who fulfill criteria for renal support 1

Prevention of HRS

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

Monitoring and Management

• Careful monitoring of urine output, fluid balance, arterial pressure, and standard vital signs is essential 2
• Patients with type 1 HRS are generally better managed in intensive or semi-intensive care units 2
• Adequate nutritional support with daily energy intake of 35-40 kcal/kg and protein intake of 1.2-1.5 g/kg 2

Prognosis

• Untreated HRS has poor prognosis, with median survival of untreated type 1 HRS approximately 1 month 2, 5
• High MELD scores and type 1 HRS are associated with very poor prognosis 2
• Even with treatment, early mortality rates are very high in the absence of liver transplantation 6