What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

First-Line Pharmacological Treatment

Terlipressin plus albumin is the definitive first-line pharmacological treatment for hepatorenal syndrome type 1 (HRS-AKI), with an initial dose of 1 mg IV every 4-6 hours, escalating to 2 mg every 4 hours if serum creatinine does not decrease by at least 25% after 3 days. 1, 2

Terlipressin Dosing Protocol

• Start with 0.85-1 mg IV every 4-6 hours 1, 3
• Increase stepwise to maximum 2 mg every 4 hours if inadequate response (defined as <25% creatinine reduction) after 3 days 1
• FDA approval indicates patients with serum creatinine >5 mg/dL are unlikely to benefit 2
• Terlipressin works by reducing portal hypertension and splanchnic vasodilation, increasing mean arterial pressure by approximately 16.2 mmHg 2

Albumin Administration with Terlipressin

• Day 1: 1 g/kg IV (maximum 100g) 1, 3
• Subsequent days: 20-40 g/day IV for up to 20 days 1, 3
• Discontinue albumin if anasarca develops, but continue vasoconstrictors 4

Alternative Vasoconstrictor Regimens

Norepinephrine Plus Albumin (First Alternative)

When terlipressin is unavailable or in ICU settings, norepinephrine plus albumin represents the best alternative, with comparable efficacy and potentially fewer adverse events. 1, 4

• Start norepinephrine at 0.5 mg/hour IV 1, 3
• Increase every 4 hours in 0.5 mg/hour increments to maximum 3 mg/hour 1, 3
• Goal: Increase mean arterial pressure by 10-15 mmHg 1
• Requires ICU monitoring 1
• Success rate of 83% reported in pilot studies 1
• Low-certainty evidence suggests fewer adverse events per participant compared to terlipressin 5

Midodrine Plus Octreotide Plus Albumin (Second Alternative)

This combination can be administered outside the ICU setting when terlipressin and norepinephrine are unavailable, though evidence shows lower recovery rates compared to terlipressin. 1, 5

• Midodrine: Titrate up to 12.5 mg orally three times daily 1, 3
• Octreotide: 200 μg subcutaneously three times daily 1, 4
• Albumin: 10-20 g IV daily for up to 20 days 1
• Can be administered at home 1
• Low-certainty evidence shows significantly lower recovery rates than terlipressin (HR 0.04,95% CrI 0.00-0.25) 5

Definitive Treatment: Liver Transplantation

Liver transplantation is the only curative treatment for hepatorenal syndrome and should be pursued with expedited referral for all patients with type 1 HRS. 1, 4, 3

• Post-transplant survival approximately 65% in HRS patients 1, 3
• Treatment with vasoconstrictors before transplantation may improve post-transplant outcomes 1
• Even if creatinine improves with medical therapy, transplant evaluation should proceed as prognosis remains poor without transplantation 1

Adjunctive and Bridge Therapies

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

• May be considered in selected patients with lower MELD scores 4
• Improves renal function and ascites control in type 2 HRS 1
• Limited evidence from small uncontrolled studies 1

Renal Replacement Therapy

• Consider for patients with worsening kidney function despite vasoconstrictors, severe fluid overload, or problematic acid-base status 4
• Continuous venovenous hemofiltration/hemodialysis may serve as bridge to transplantation 1
• Should not be first-line therapy 6

Diagnostic Prerequisites Before Treatment

Mandatory diagnostic paracentesis must be performed to exclude spontaneous bacterial peritonitis before initiating HRS treatment. 1, 3

Diagnostic Criteria to Confirm

• Advanced cirrhosis with ascites 1
• Serum creatinine >1.5 mg/dL 1
• No improvement after ≥2 days of diuretic withdrawal and volume expansion with albumin 1
• Absence of shock 1
• No current or recent nephrotoxic drug exposure 1
• Absence of parenchymal kidney disease 1

Prevention Strategies

In Spontaneous Bacterial Peritonitis

• IV albumin reduces risk of HRS development 3, 7

In Advanced Cirrhosis

• Norfloxacin 400 mg/day reduces HRS incidence 1, 3

In Severe Alcoholic Hepatitis

• Pentoxifylline 400 mg three times daily prevents HRS development 1, 3, 7

Critical Management Considerations

Volume Management with Anasarca

• When anasarca develops, discontinue albumin immediately but continue vasoconstrictors 4
• Implement sodium restriction (<2g/day) 4
• Consider diuretic therapy for volume overload 4
• Fluid restriction to <1000 mL/day only if serum sodium <125 mEq/L 4

Monitoring Parameters

• Monitor central venous pressure ideally 1
• Daily weights and fluid balance 4
• Serum creatinine every 2-3 days 1
• Mean arterial pressure and heart rate 2

Common Pitfalls to Avoid

• Do not delay transplant evaluation even if creatinine improves with medical therapy 1
• Do not continue albumin in the setting of severe volume overload/anasarca 4
• Do not use vasoconstrictors in patients with serum creatinine >5 mg/dL (unlikely to benefit) 2
• Do not stop vasoconstrictors when albumin is discontinued for anasarca 4

Expected Response Rates

• Terlipressin reverses HRS in approximately 35-45% of patients 4, 6
• Recovery may be partial even in defined responders 6
• Median survival without transplantation: 2 weeks for type 1 HRS, 6 months for type 2 HRS 6