What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

Terlipressin plus albumin is the first-line pharmacological treatment for hepatorenal syndrome with acute kidney injury (HRS-AKI), starting at 1 mg IV every 4-6 hours, combined with albumin 1 g/kg (maximum 100 g) on day 1, followed by 20-40 g/day, while liver transplantation remains the definitive curative treatment. 1, 2

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm the diagnosis by meeting all criteria: 1, 3

• Cirrhosis with ascites and serum creatinine >1.5 mg/dL
• No improvement after 2 consecutive days of diuretic withdrawal and volume expansion with albumin
• Absence of shock, nephrotoxic drug exposure, and structural kidney disease (proteinuria <0.5 g/day, <50 RBCs/HPF, normal renal ultrasound)
• Perform diagnostic paracentesis to exclude spontaneous bacterial peritonitis (SBP), which precipitates HRS and requires specific treatment with antibiotics plus albumin 1, 2

First-Line Pharmacological Treatment: Terlipressin Plus Albumin

The European Association for the Study of the Liver and American College of Gastroenterology recommend terlipressin as first-line therapy, achieving HRS reversal in 64-76% of patients. 1, 2

Dosing Protocol:

• Terlipressin: Start 1 mg IV every 4-6 hours 1, 2
• If serum creatinine doesn't decrease by ≥25% after 3 days, increase stepwise to maximum 2 mg every 4 hours 1, 2
• Albumin: 1 g/kg (maximum 100 g) on day 1, then 20-40 g/day 1, 2
• Continue until complete response (creatinine ≤1.5 mg/dL on two occasions) or maximum 14 days 1, 2

Important Limitation:

Patients with serum creatinine >5 mg/dL are unlikely to benefit from terlipressin. 4

Alternative Pharmacological Treatments

When Terlipressin is Unavailable: Midodrine + Octreotide + Albumin

The American Association for the Study of Liver Diseases recommends this combination as an alternative, which can be administered outside the ICU and even at home. 1, 2

Dosing: 1, 2

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

Critical pitfall: Never use octreotide as monotherapy—it requires midodrine to be effective, as two studies definitively showed octreotide alone provides no benefit. 2

ICU-Based Alternative: Norepinephrine Plus Albumin

Norepinephrine plus albumin achieves 83% success rate in reversing HRS-AKI but requires ICU admission with central venous access. 1, 2

Dosing: 1, 2

• Norepinephrine: 0.5-3.0 mg/hour IV, titrated to increase mean arterial pressure by 15 mmHg
• Albumin: 20-40 g/day
• Warning: Attempting peripheral administration of norepinephrine risks tissue necrosis—central access is mandatory 1

Monitoring Treatment Response

Check serum creatinine every 2-3 days to assess response: 1, 2

• Complete response: Creatinine ≤1.5 mg/dL on two occasions
• Partial response: Creatinine decrease ≥25% but still >1.5 mg/dL
• Monitor for complications: cardiac/intestinal ischemia, pulmonary edema, distal necrosis with terlipressin 1
• Discontinue albumin if anasarca develops, but continue vasoconstrictors 1

Definitive Treatment: Liver Transplantation

Liver transplantation is the only curative treatment for HRS, with post-transplant survival rates of approximately 65% in HRS-AKI patients. 1, 3

• Expedited referral for transplantation is recommended for all patients with HRS-AKI 1, 3
• Treatment with vasoconstrictors before transplantation may improve post-transplant outcomes 1
• Important: The reduction in creatinine and MELD score after vasoconstrictor treatment should not change the decision to perform liver transplantation, as prognosis remains poor without transplant 1

Prevention Strategies

Prevention is crucial in high-risk situations: 1, 2, 3

In Spontaneous Bacterial Peritonitis:

Albumin 1.5 g/kg at diagnosis of SBP, then 1 g/kg on day 3, reduces HRS incidence from 30% to 10% and mortality from 29% to 10%. 1, 2

In Advanced Cirrhosis:

• Norfloxacin 400 mg/day reduces HRS incidence in advanced cirrhosis 1, 3
• Pentoxifylline 400 mg three times daily prevents HRS in severe alcoholic hepatitis 1, 3

Adjunctive Therapies

Transjugular Intrahepatic Portosystemic Shunt (TIPS):

TIPS improves renal function and ascites control in Type 2 HRS, though evidence for Type 1 HRS is limited to small uncontrolled studies. 1

Renal Replacement Therapy:

Consider continuous venovenous hemofiltration/hemodialysis only as a bridge to liver transplantation in patients unresponsive to vasoconstrictors—it should not be first-line therapy. 1, 5

Critical Pitfalls to Avoid

• Never delay treatment waiting for complete diagnostic workup if HRS-AKI is suspected—early treatment improves outcomes 1, 6
• Avoid nephrotoxic drugs and diuretics in patients at high risk 1
• Do not use hydroxyethyl starch or other artificial colloids as albumin substitutes—they are associated with harm in patients at risk of AKI 2
• Patients require ICU or semi-ICU level monitoring with central venous pressure monitoring to guide fluid management 1, 3