What is the management of hepatorenal syndrome?

Management of Hepatorenal Syndrome

First-Line Treatment

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

• Albumin should be administered at 1 g/kg body weight on day 1 (maximum 100 g), followed by 20-40 g/day until complete response or for a maximum of 14 days 1
• Monitor serum creatinine every 2-3 days to assess treatment response, with complete response defined as serum creatinine ≤1.5 mg/dL on two occasions 1

Alternative Treatment When Terlipressin Is Unavailable

When terlipressin is not available, use midodrine plus octreotide plus albumin as the alternative regimen. 1, 2

• Start midodrine at 7.5 mg orally three times daily, titrating up to a maximum of 12.5 mg three times daily 1, 2
• Administer octreotide at 100-200 μg subcutaneously three times daily 1, 2
• Give albumin at 10-20 g IV daily for up to 20 days 1, 2
• This combination can be administered outside the ICU and even at home 1
• Critical caveat: Never use octreotide as monotherapy—it requires midodrine to be effective, as two studies definitively showed octreotide alone provides no benefit 1

Evidence Supporting Alternative Treatment

A 2009 study demonstrated that midodrine/octreotide/albumin significantly improved transplant-free survival compared to controls (median survival 101 days versus 18 days, P<0.0001), with benefits in both HRS type 1 and type 2 3. However, a more recent 2021 randomized controlled trial showed norepinephrine was superior to midodrine/octreotide, achieving full response in 57.6% versus 20% of patients (p=0.006) 4.

Third-Line Option: Norepinephrine

Norepinephrine plus albumin is an effective alternative but requires ICU admission. 1, 2

• Administer norepinephrine at 0.5-3.0 mg/hour IV with the goal of increasing mean arterial pressure by 15 mmHg 1, 2
• This regimen achieved an 83% success rate in reversing type 1 HRS in pilot studies 1
• Based on the most recent high-quality evidence, norepinephrine is more effective than midodrine/octreotide when ICU resources are available 4

Definitive Treatment

Liver transplantation is the definitive treatment for both type 1 and type 2 HRS and should be pursued with expedited referral for type 1 HRS. 1, 2, 5

• Post-transplant survival rates are approximately 65% in type 1 HRS 1, 2, 5
• Treatment of HRS before transplantation with vasoconstrictors may improve post-transplant outcomes 2
• Important consideration: The reduction in serum creatinine and MELD score after treatment should not change the decision to perform liver transplantation, as prognosis after recovering from HRS remains poor 2

Prevention Strategies

Albumin administration with antibiotics in spontaneous bacterial peritonitis is fundamental for preventing HRS. 1

• Give 1.5 g/kg body weight at diagnosis, followed by 1 g/kg on day 3 1
• This reduces HRS type 1 incidence from 30% to 10% and mortality from 29% to 10% compared to cefotaxime alone 1
• Patients with high bilirubin (≥4 mg/dL) or high creatinine (≥1 mg/dL) are at higher risk and may particularly benefit 1

Additional Preventive Measures

• Norfloxacin 400 mg/day reduces HRS incidence in advanced cirrhosis 1, 2, 5
• Pentoxifylline 400 mg three times daily prevents HRS in severe alcoholic hepatitis 1, 2, 5
• Avoid nephrotoxic drugs in patients with advanced cirrhosis 1

Diagnostic Criteria Before Treatment

Before initiating treatment, confirm HRS diagnosis by meeting all of the following criteria: 1, 2, 5

• Cirrhosis with ascites
• Serum creatinine >1.5 mg/dL
• No improvement after at least 2 days of diuretic withdrawal and volume expansion with albumin
• Absence of shock
• No current or recent nephrotoxic drug exposure
• Absence of parenchymal kidney disease
• Perform diagnostic paracentesis to rule out spontaneous bacterial peritonitis, which can precipitate HRS 2, 5

Adjunctive Therapies for Type 2 HRS

Transjugular intrahepatic portosystemic shunt (TIPS) improves renal function and ascites control in type 2 HRS. 2

• TIPS has shown effectiveness in uncontrolled studies, though more evidence is needed 1, 2
• Consider TIPS for patients with type 2 HRS who have refractory ascites 2

Critical Contraindications

Avoid or discontinue albumin in patients with: 1

• Head trauma (associated with damage)
• Anasarca (severe volume overload)
• Hemorrhagic shock (prefer isotonic crystalloids instead)

Do not replace albumin with starch solutions or hydroxyethyl starch—these are associated with harm in patients at risk of acute kidney injury and show no beneficial effect on circulatory function in spontaneous bacterial peritonitis. 1

Monitoring Parameters

• Monitor serum creatinine every 2-3 days 1
• Track urine output, fluid balance, arterial pressure, and standard vital signs 5
• Central venous pressure should ideally be monitored to help manage fluid balance 2, 5
• Patients with type 1 HRS are generally better managed in intensive or semi-intensive care units 5