What is the treatment for Hepatorenal Syndrome (HRS)?

Treatment of Hepatorenal Syndrome

Terlipressin plus albumin is the first-line pharmacological treatment for HRS-AKI (Type 1 HRS), with liver transplantation being the only definitive cure. 1, 2

Immediate Management Algorithm

First-Line Pharmacological Treatment

Terlipressin plus albumin should be initiated immediately upon diagnosis of Type 1 HRS (HRS-AKI): 1, 2

• Terlipressin dosing: Start with 1 mg IV bolus every 4-6 hours 1, 2
• Albumin dosing: 1 g/kg on day 1 (maximum 100 g), followed by 20-40 g/day thereafter 2, 3
• Dose escalation: If serum creatinine does not decrease by at least 25-30% after 3-4 days, increase terlipressin stepwise to a maximum of 2 mg every 4 hours 1, 2
• Treatment duration: Continue until serum creatinine decreases below 1.5 mg/dL or for a maximum of 14 days 2
• Discontinuation criteria: Stop within 14 days if there is no response or only partial response, or if serum creatinine remains at or above baseline on Day 4 2, 3

The FDA-approved TERLIVAZ (terlipressin) demonstrated a 29.1% verified HRS reversal rate compared to 15.8% with placebo in the CONFIRM trial, with durability of response at 31.7% versus 15.8% 3

Alternative Pharmacological Regimens

When terlipressin is unavailable (as in many U.S. centers), use midodrine plus octreotide plus albumin: 1, 2

• Midodrine: Start at 7.5 mg orally three times daily, titrate up to 12.5 mg three times daily 1, 2
• Octreotide: 100-200 μg subcutaneously three times daily 1, 2
• Albumin: 10-20 g IV daily for up to 20 days 1

This combination can be administered outside the ICU and even at home, providing practical advantages in resource-limited settings 1

Norepinephrine plus albumin as rescue therapy or ICU-based alternative: 1, 4

• Setting: Requires ICU monitoring, though recent evidence suggests feasibility in non-ICU settings with appropriate monitoring 4
• Dosing: Start at 5 mcg/minute, titrate to increase mean arterial pressure by 15 mmHg above baseline 1, 4
• Efficacy: 45% response rate when used as rescue therapy after midodrine-octreotide failure, with 83% success rate reported in pilot studies 1, 4
• Important caveat: Achieving MAP increase of ≥10 mmHg is associated with greater probability of response 4

Type 2 HRS Management

The same vasoconstrictor regimens used for Type 1 HRS can be applied to Type 2 HRS, though with less urgency: 2

Transjugular intrahepatic portosystemic shunt (TIPS) is particularly applicable for Type 2 HRS: 1, 2

• TIPS improves renal function and controls ascites in Type 2 HRS patients 1, 2
• More suitable for Type 2 than Type 1 HRS due to the more stable clinical condition 2
• Limited evidence exists for Type 1 HRS (only 7 patients in uncontrolled study) 1

Definitive Treatment

Liver transplantation is the definitive treatment for both Type 1 and Type 2 HRS and should be pursued urgently: 1, 2

• Survival rates: Approximately 65% post-transplant survival in Type 1 HRS 1, 2
• Priority status: Patients with Type 1 HRS should receive expedited referral and priority for transplantation due to high mortality on waiting list 1, 2
• Pre-transplant treatment benefit: Treatment of HRS with vasoconstrictors before transplantation may improve post-transplant outcomes 1, 2
• Combined transplant consideration: No advantage to combined liver-kidney transplantation versus liver alone, except in patients requiring prolonged renal replacement therapy (>12 weeks) 2

Prevention Strategies

Implement preventive measures in high-risk patients with advanced cirrhosis: 1, 2

• Norfloxacin 400 mg/day: Reduces HRS incidence in advanced cirrhosis 1, 2
• Albumin with antibiotics for SBP: Albumin infusion together with antibiotics when treating spontaneous bacterial peritonitis reduces risk of developing HRS and improves survival 2
• Pentoxifylline 400 mg three times daily: Prevents HRS development in patients with severe alcoholic hepatitis 1, 2
• Diagnostic paracentesis: Must be performed to rule out spontaneous bacterial peritonitis, which is the most important precipitating factor for Type 1 HRS 1, 2

Monitoring and Supportive Care

Close monitoring is essential during vasoconstrictor therapy: 1

• Monitor urine output, fluid balance, arterial pressure, and standard vital signs 5
• Central venous pressure should ideally be monitored to help manage fluid balance 1, 5
• Patients with Type 1 HRS are generally better managed in intensive or semi-intensive care units 5

Renal replacement therapy considerations: 1, 2

• Continuous venovenous hemofiltration/hemodialysis may be considered as a bridge to liver transplantation in selected patients 1
• Should not be used as first-line therapy 6
• Very limited data exists on artificial liver support systems 1

Critical Pitfalls to Avoid

Do not delay treatment while awaiting transplant evaluation - median survival of untreated Type 1 HRS is approximately 1 month 2, 5

Do not assume HRS reversal changes transplant priority - the reduction in serum creatinine and MELD score after treatment should not change the decision to perform liver transplantation, as prognosis after recovering from HRS remains poor 1

Exclude other causes before diagnosing HRS: Diagnosis requires excluding shock, nephrotoxic drugs, parenchymal kidney disease, and ensuring no improvement after at least 2 days of diuretic withdrawal and volume expansion with albumin 1, 5

Monitor for terlipressin adverse events: The most common treatment-related adverse events include respiratory failure and ischemic events; norepinephrine can cause arrhythmias in up to 25% of patients 3, 4