What is the treatment for Hepatorenal Syndrome (HRS)?

Treatment of Hepatorenal Syndrome (HRS)

Terlipressin plus albumin is the first-line treatment for hepatorenal syndrome, with norepinephrine plus albumin as an effective alternative when terlipressin is unavailable. 1, 2

Diagnostic Criteria for HRS

Before initiating treatment, confirm HRS diagnosis with:

• Presence of cirrhosis with ascites
• Acute kidney injury (AKI) with serum creatinine ≥2.25 mg/dL
• No improvement in renal function after diuretic withdrawal and albumin administration
• Absence of shock, sepsis, or nephrotoxic drug use
• No evidence of intrinsic kidney disease

Treatment Algorithm

Step 1: Initial Management

• Withdraw diuretics and nephrotoxic medications
• Volume expansion with albumin: 1 g/kg on day 1 (maximum 100g), followed by 20-40 g/day 3, 1
• Identify and treat precipitating factors (infections, GI bleeding, etc.)

Step 2: Vasoconstrictor Therapy

First-line: Terlipressin + Albumin

• Initial dose: 1 mg terlipressin IV every 4-6 hours 2
• If serum creatinine decreases <25% after 2 days, increase dose in stepwise manner up to 2 mg every 4-6 hours (maximum 12 mg/day) 2
• Continue until serum creatinine decreases below 1.5 mg/dL or for maximum 14 days 2
• Continuous IV infusion (2-12 mg/24h) is equally effective with fewer side effects than bolus administration 2

Alternative options when terlipressin is unavailable:

1. Norepinephrine + Albumin 2

   • Dose: 0.5-3 mg/hour as continuous infusion
   • Requires ICU setting and central venous access
   • Similar efficacy to terlipressin 2

2. Midodrine + Octreotide + Albumin 1, 4

   • Midodrine: Start at 7.5 mg orally three times daily, titrate up to 12.5 mg three times daily
   • Octreotide: 100 μg subcutaneously three times daily, increase to 200 μg three times daily
   • Less effective than terlipressin (28.6% vs 70.4% recovery rate) 5

Step 3: Monitor Response

• Check serum creatinine daily
• Monitor blood pressure, heart rate, and urine output
• Watch for ischemic complications (cardiac, intestinal, digital)
• Response predictors: increase in mean arterial pressure ≥5 mmHg, baseline creatinine <3 mg/dL, bilirubin <10 mg/dL 1

Step 4: Additional Interventions

• TIPS (Transjugular Intrahepatic Portosystemic Shunt) 2, 6

  • Consider in selected patients who respond partially to medical therapy
  • Contraindicated in severe liver failure, significant encephalopathy

• Renal Replacement Therapy 2, 1

  • Bridge to liver transplantation in non-responders to vasoconstrictors
  • Indications: severe electrolyte/acid-base disturbances, volume overload, uremia

• Liver Transplantation 1

  • Definitive treatment for HRS
  • Expedite referral for all eligible patients

Treatment Response Classification

• Complete response: Final serum creatinine within 0.3 mg/dL from baseline value 2
• Partial response: Regression of AKI stage with final serum creatinine ≥0.3 mg/dL from baseline 2

Important Considerations

• Terlipressin has significantly higher rates of renal function recovery compared to midodrine/octreotide (70.4% vs 28.6%) 5
• Recurrence after treatment withdrawal is common, especially in HRS type 2 2
• Adverse effects of vasoconstrictors include ischemic and cardiovascular events; perform ECG screening before starting treatment 2
• Early treatment initiation is associated with better outcomes; higher baseline creatinine predicts poorer response 1
• Median survival without treatment is approximately 3 months 1

Liver transplantation remains the only curative treatment for HRS, and all other therapies should be considered as bridges to transplantation when possible 7, 1.