What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

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

First-Line Pharmacological Treatment

Terlipressin plus albumin should be initiated immediately for HRS-AKI (Type 1 HRS) with the following dosing regimen: 1, 3

• Initial dose: 1 mg IV every 4-6 hours 1
• Dose escalation: If serum creatinine does not decrease by at least 25% after 3 days, increase stepwise to a maximum of 2 mg every 4 hours 1, 3
• Duration: Continue until complete response or maximum 14 days for partial response 3
• Albumin dosing: 1 g/kg on day 1 (maximum 100g) followed by 20-40g/day 4

Important limitation: Patients with serum creatinine >5 mg/dL are unlikely to benefit from terlipressin. 2

The mechanism involves reducing portal hypertension and splanchnic vasodilation while increasing effective arterial volume and mean arterial pressure by approximately 16.2 mmHg. 2

Alternative Vasoconstrictor Regimens

When terlipressin is unavailable or contraindicated, use one of these alternatives: 1, 3

Midodrine + Octreotide + Albumin (Outpatient Option)

• Midodrine: Titrate up to 12.5 mg orally three times daily 1, 4
• Octreotide: 200 μg subcutaneously three times daily 1, 4
• Albumin: 10-20 g IV daily for up to 20 days 1
• Advantage: Can be administered outside ICU and even at home 3

Norepinephrine + Albumin (ICU Only)

• Norepinephrine: 0.5-3.0 mg/h to increase mean arterial pressure by 15 mmHg 1, 4
• Success rate: 83% reported in pilot studies 3
• Requirement: Must be administered in ICU setting 1, 3

Critical point: Continue vasoconstrictors even if albumin must be discontinued due to volume overload/anasarca. 4

Definitive Treatment: Liver Transplantation

Liver transplantation is the only curative treatment and should be pursued urgently for all HRS patients. 1, 3

• Expedited referral: Mandatory for Type 1 HRS (HRS-AKI) 1, 3
• Post-transplant survival: Approximately 65% in Type 1 HRS 1, 3
• Pre-transplant treatment benefit: Treating HRS with vasoconstrictors before transplantation may improve post-transplant outcomes 1, 3

Important caveat: Even if serum creatinine improves with treatment and MELD score decreases, this should NOT change the decision to proceed with liver transplantation, as prognosis after HRS recovery remains poor without transplant. 1

Adjunctive and Bridge Therapies

Renal Replacement Therapy

Consider in patients with: 4

• Worsening kidney function despite vasoconstrictor therapy
• Severe fluid overload despite diuretic therapy
• Problematic acid-base status
• As a bridge to liver transplantation in selected patients 1

TIPS (Transjugular Intrahepatic Portosystemic Shunt)

• Type 2 HRS: Improves renal function and ascites control 1
• Type 1 HRS: Limited evidence (uncontrolled study of 7 patients) 1, 3
• Patient selection: Consider in selected patients with lower MELD scores 4

Prevention Strategies

Implement these measures in high-risk patients: 1, 3

• Spontaneous bacterial peritonitis: Albumin infusion with antibiotics 3
• Advanced cirrhosis: Norfloxacin 400 mg/day 1, 3
• Severe alcoholic hepatitis: Pentoxifylline 400 mg three times daily 1, 3
• Large-volume paracentesis (>5L): Albumin 6-8g per liter of ascites removed 4
• Avoid nephrotoxic drugs in all patients with advanced cirrhosis 3

Critical Diagnostic Prerequisites

Before initiating treatment, confirm HRS diagnosis by ensuring: 1, 3

• Cirrhosis with ascites present
• 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
• Diagnostic paracentesis performed to rule out spontaneous bacterial peritonitis 1, 3

Common Pitfalls to Avoid

• Do not delay liver transplant referral even if creatinine improves with medical therapy 1
• Do not discontinue vasoconstrictors when albumin is stopped due to anasarca 4
• Do not use terlipressin in patients with creatinine >5 mg/dL (unlikely to benefit) 2
• Monitor for ischemic complications with terlipressin (cardiovascular, respiratory, peripheral) 2
• Differentiate HRS from acute tubular necrosis as vasoconstrictors are not justified for ATN 5