What is the management of hepatorenal syndrome?

Management of Hepatorenal Syndrome

Terlipressin plus albumin is the first-line pharmacological treatment for hepatorenal syndrome, with liver transplantation remaining the only definitive cure. 1, 2, 3

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis by:

• Performing diagnostic paracentesis to exclude spontaneous bacterial peritonitis, which can precipitate HRS and requires specific treatment with antibiotics plus albumin 1, 2
• Ensuring 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 nephrotoxic drug exposure, and absence of parenchymal kidney disease 2, 4
• Using AKI staging criteria (Stage 1: creatinine increase ≥0.3 mg/dL or 1.5-2x baseline; Stage 2: 2-3x baseline; Stage 3: >3x baseline or >4 mg/dL with acute increase ≥0.3 mg/dL) 1, 4

Important caveat: Patients with serum creatinine >5 mg/dL are unlikely to benefit from vasoconstrictor therapy 3

First-Line Treatment: Terlipressin Plus Albumin

Start terlipressin 1 mg IV every 4-6 hours plus albumin 1 g/kg (maximum 100 g) on day 1, followed by 20-40 g/day 1, 2, 4

Dosing Algorithm:

• Initial dose: Terlipressin 0.5-1 mg IV every 4-6 hours 1, 2
• Dose escalation: If serum creatinine does not decrease by ≥25% after 3 days, increase stepwise to maximum 2 mg every 4 hours 1, 2
• Duration: Continue until complete response (creatinine ≤1.5 mg/dL) or maximum 14 days for partial response 1, 2
• Alternative administration: Continuous IV infusion (2-12 mg/24 hours) may reduce adverse events while maintaining efficacy 1

Evidence Strength:

Terlipressin plus albumin achieves reversal of HRS in 64-76% of patients 1, with significantly superior outcomes compared to albumin alone (43.5% vs 8.7% improvement, P=0.017) 5 and compared to midodrine/octreotide/albumin (70.4% vs 28.6%, P=0.01) 6

Monitoring Adverse Effects:

Watch for cardiovascular complications including cardiac or intestinal ischemia, pulmonary edema, and distal necrosis 1, 7. Permanent withdrawal is required in only a minority of cases 5

Second-Line Treatment: Norepinephrine Plus Albumin

If terlipressin is unavailable or the patient is already in ICU, use norepinephrine 0.5-3 mg/hour IV plus albumin 1, 2, 7

• Goal: Increase mean arterial pressure by 10-15 mmHg 2, 7
• Efficacy: Meta-analyses show no significant difference between norepinephrine plus albumin and terlipressin plus albumin in HRS reversal rates 1, 7
• Success rate: 83% in reversing type 1 HRS in pilot studies 2, 7
• Requirement: Central venous access and traditionally ICU monitoring, though feasibility outside ICU has been demonstrated 7

Third-Line Treatment: Midodrine Plus Octreotide Plus Albumin

Only use this combination when terlipressin and norepinephrine are both unavailable, as it is significantly less effective 1, 2, 7

• Midodrine: Start 7.5 mg orally three times daily, titrate to maximum 12.5 mg three times daily 1, 2, 4
• Octreotide: 100-200 μg subcutaneously three times daily 1, 2, 4
• Albumin: 10-20 g IV daily for up to 20 days 1, 2
• Advantage: Can be administered outside ICU and even at home 1, 2
• Evidence limitation: Retrospective data shows reduced mortality (43% vs 71%, P<0.05) but randomized trial shows only 28.6% response rate versus 70.4% with terlipressin 1, 6

Critical pitfall: Never use octreotide alone—it is ineffective without midodrine 1, 7

Definitive Treatment: Liver Transplantation

Expedite referral for liver transplantation in all HRS patients, as this is the only curative treatment 2, 4, 8

• Post-transplant survival in type 1 HRS is approximately 65% 2, 4
• Treatment with vasoconstrictors before transplantation may improve post-transplant outcomes 2, 4
• Even if serum creatinine improves with medical therapy, proceed with transplantation as prognosis remains poor without it 2

Adjunctive Therapies

Transjugular Intrahepatic Portosystemic Shunt (TIPS):

• May improve renal function and ascites control in type 2 HRS 2
• Limited evidence for type 1 HRS; cannot be recommended as standard therapy 2, 7
• Many patients have contraindications limiting applicability 7

Renal Replacement Therapy:

• Consider only as bridge to liver transplantation in patients unresponsive to vasoconstrictors 1, 2, 7
• Prognosis with dialysis alone is very poor without planned transplantation 1

Prevention Strategies

Implement these measures in high-risk cirrhotic patients:

• For spontaneous bacterial peritonitis: Albumin 1.5 g/kg at diagnosis, then 1 g/kg on day 3, reduces HRS incidence from 30% to 10% and mortality from 29% to 10% 1, 4
• For advanced cirrhosis: Norfloxacin 400 mg/day reduces HRS incidence 2, 4
• For severe alcoholic hepatitis: Pentoxifylline 400 mg three times daily prevents HRS development 2, 4
• Avoid nephrotoxic drugs in all patients with advanced cirrhosis 4, 7

Monitoring Treatment Response

• Check serum creatinine every 2-3 days to assess response 4
• Complete response: Creatinine ≤1.5 mg/dL on two occasions 4
• Monitor mean arterial pressure, urine output, and serum sodium 7
• Response characterized by progressive creatinine reduction, increased arterial pressure, increased urine volume, and increased serum sodium 7