What is the treatment for hepatocardiorenal syndrome?

Treatment of Hepatocardiorenal Syndrome

The first-line treatment for hepatocardiorenal syndrome is terlipressin plus albumin, which improves renal function in 35-45% of patients with acute kidney injury-hepatorenal syndrome (AKI-HRS) and improves short-term survival. 1, 2

Diagnostic Criteria

• Diagnosis requires excluding other causes of acute kidney injury in cirrhotic patients with:
  • Advanced cirrhosis with ascites
  • Serum creatinine >1.5 mg/dL
  • No improvement after ≥2 days of diuretic withdrawal and volume expansion with albumin
  • Absence of shock
  • No current/recent nephrotoxic drug exposure
  • Absence of parenchymal kidney disease 1

Pharmacological Management

First-Line Therapy

• Terlipressin plus albumin:
  • Initial dose: 0.5-1 mg IV every 4-6 hours
  • Increase stepwise to maximum of 2 mg every 4 hours if serum creatinine doesn't decrease by ≥25% after 3 days
  • Continue until complete response or maximum of 14 days for partial response 3, 1
  • Continuous infusion (2-12 mg/24h) is as effective as bolus dosing with fewer adverse events 3

Alternative Therapies (when terlipressin unavailable)

• Norepinephrine plus albumin:

  • Administered as continuous infusion (0.5-3 mg/h)
  • Requires ICU setting
  • Goal: increase mean arterial pressure by 15 mmHg 3, 1
  • Similar efficacy to terlipressin in reversibility of HRS 3

• Midodrine plus octreotide plus albumin:

  • 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 3, 1
  • Less effective than terlipressin and should not be first choice 3

Albumin Administration

• Initial dose: 1 g/kg before starting vasoconstrictor treatment
• Maintenance: 20-40 g/day during treatment 3
• Improves systemic hemodynamics by increasing cardiac output 3

Definitive Treatment

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

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

• May improve renal function in selected patients with type 1 HRS 3
• Limited applicability due to contraindications in many patients 3
• Can be considered in appropriately selected patients who meet criteria similar to published trials 3
• Converts diuretic-resistant patients into diuretic-sensitive patients 3

Renal Replacement Therapy

• Consider for patients who don't respond to vasoconstrictor therapy 3
• Used to control azotemia and maintain electrolyte balance before liver transplantation 3
• Hypotension during dialysis is a common problem 3
• Without transplantation, survival remains poor 3

Prevention of HRS

• Norfloxacin (400 mg/day) reduces the incidence of HRS in advanced cirrhosis 3
• Pentoxifylline (400 mg three times daily) may prevent HRS development in patients with severe alcoholic hepatitis 3
• Systematic search for infection including microbiological and cytological examination of ascites fluid is crucial 3

Important Considerations and Pitfalls

• Response rates are significantly lower in recurrent HRS (20% of cases) 3
• Adverse events of terlipressin include cardiac or intestinal ischemia, pulmonary edema, and distal necrosis 3
• Reduction in serum creatinine after treatment should not change the decision to perform liver transplantation 3
• Combined liver-kidney transplantation offers no advantage over liver transplantation alone except in patients on prolonged renal support (>12 weeks) 3