What is the treatment approach for Hepatorenal Syndrome (HRS) Type 1 and Type 2?

Treatment Approach for Hepatorenal Syndrome (HRS) Type 1 and Type 2

Terlipressin plus albumin should be considered the first-line treatment for HRS Type 1, while liver transplantation remains the definitive treatment for both HRS Type 1 and Type 2. 1, 2

Diagnosis and Classification

Before initiating treatment, proper diagnosis is essential:

• HRS is diagnosed by demonstrating increased serum creatinine (>133 μmol/L or 1.5 mg/dL) and excluding other causes of renal failure
• Causes to exclude: hypovolemia, shock, parenchymal renal diseases, and nephrotoxic drugs 1
• Current classification:
  • HRS-AKI (formerly Type 1): Rapid deterioration of renal function, often triggered by precipitating events
  • HRS-CKD (formerly Type 2): Stable, less severe kidney dysfunction with slower progression 2

Treatment Algorithm for HRS Type 1 (HRS-AKI)

First-Line Treatment

1. Terlipressin plus albumin 1, 2, 3
   • Terlipressin: Start at 1 mg IV every 4-6 hours
   • If serum creatinine doesn't decrease by at least 25% after 3 days, increase dose stepwise to maximum 2 mg every 4-6 hours
   • Albumin: 1 g/kg on day 1, followed by 20-40 g/day
   • Continue until serum creatinine decreases below 133 μmol/L (1.5 mg/dL) or for maximum 14 days
   • Response rate: 40-50% of patients

Alternative Treatments (if terlipressin unavailable or contraindicated)

1. Norepinephrine plus albumin (in ICU setting) 2
2. Midodrine + octreotide + albumin 2
   • Midodrine: Titrate up to 12.5 mg orally three times daily
   • Octreotide: 200 μg subcutaneously three times daily
   • Albumin: 10-20 g/day IV for up to 20 days

Non-Responders

1. Renal replacement therapy as a bridge to transplantation 1, 2

   • Consider for patients who don't respond to vasoconstrictors and meet criteria for renal support
   • Limited data on effectiveness

2. Transjugular Intrahepatic Portosystemic Shunt (TIPS) 1

   • May improve renal function in selected patients
   • Limited applicability due to frequent contraindications in HRS-1 patients

Definitive Treatment

Liver transplantation is the treatment of choice with survival rates of approximately 65% in HRS Type 1 1

Treatment Algorithm for HRS Type 2 (HRS-CKD)

1. Management of refractory ascites 2

   • Focus on treating the underlying ascites

2. TIPS may be more applicable for HRS Type 2 than for HRS Type 1 1, 2

   • Can improve renal function and control of ascites

3. Vasoconstrictors plus albumin are not routinely recommended due to high recurrence after withdrawal 2

4. Liver transplantation is the definitive treatment 1, 2

Monitoring and Prognosis

• Daily assessment of serum creatinine, blood pressure, heart rate, urine output, and signs of ischemic complications 2
• If creatinine remains at or above pretreatment level over 4 days with maximum tolerated doses, consider discontinuing therapy 2
• Prognosis remains poor despite treatment:
  • Median survival of approximately 3 months for all HRS patients
  • Untreated Type 1 HRS has median survival of approximately 1 month 1

Important Considerations

• Prevention: Treatment of spontaneous bacterial peritonitis (SBP) with albumin plus antibiotics reduces the risk of HRS development 1
• Liver-kidney transplantation: Consider for patients who have been under prolonged renal support therapy (>12 weeks) 1
• Cardiovascular monitoring: Terlipressin can cause cardiovascular or ischemic complications in approximately 12% of patients 1
• Treatment before transplantation: Although not studied prospectively, treatment of HRS before transplantation may improve outcomes after transplantation 1

Terlipressin Efficacy and Safety

The CONFIRM trial demonstrated that terlipressin was more effective than placebo in improving renal function in HRS-1 patients (32% vs 17% achieved verified HRS reversal), but was associated with serious adverse events including respiratory failure 3, 4. Careful monitoring for side effects is essential.