What is the initial treatment for hepatorenal syndrome?

Initial Treatment for Hepatorenal Syndrome

The first-line treatment for hepatorenal syndrome type 1 (HRS-AKI) is terlipressin plus albumin, with terlipressin 0.5-1 mg IV every 4-6 hours and albumin 1 g/kg body weight on day 1 (maximum 100 g), followed by 20-40 g/day, continued until complete response or for a maximum of 14 days. 1

Treatment Algorithm Based on Drug Availability and Setting

First-Line: Terlipressin Plus Albumin (Where Available)

• Start terlipressin 1 mg IV every 4-6 hours plus albumin 1 g/kg (maximum 100 g) on day 1, followed by 20-40 g/day 1, 2
• If serum creatinine doesn't decrease by at least 25% after 3 days, increase terlipressin stepwise to a maximum of 2 mg every 4 hours 1, 2
• This combination achieves reversal of HRS in 64-76% of patients, significantly superior to albumin alone 2
• Continue treatment until complete response (creatinine ≤1.5 mg/dL on two occasions) or maximum 14 days 1, 2

Alternative: Midodrine Plus Octreotide Plus Albumin (When Terlipressin Unavailable)

• Start midodrine 7.5 mg orally three times daily, titrate up to maximum 12.5 mg three times daily 1, 2
• Add octreotide 100-200 μg subcutaneously three times daily (never use octreotide as monotherapy—it requires midodrine to be effective) 1
• Give albumin 10-20 g IV daily for up to 20 days 1, 2
• This combination can be administered outside the ICU and even at home, with reduced mortality (43% versus 71% in controls) 1
• The American Association for the Study of Liver Diseases recommends this as the standard alternative when terlipressin is not available 1, 2

Third-Line: Norepinephrine Plus Albumin (ICU Setting Required)

• Norepinephrine 0.5-3.0 mg/hour IV titrated to increase mean arterial pressure by 15 mmHg 1, 2
• Requires ICU admission with central venous access and continuous hemodynamic monitoring 1, 2
• Success rate of 83% in reversing type 1 HRS in pilot studies 1
• Never attempt peripheral administration—risks tissue necrosis 2

Critical Pre-Treatment Steps

• Perform diagnostic paracentesis immediately to rule out spontaneous bacterial peritonitis, which precipitates HRS and requires specific treatment with antibiotics plus albumin 2
• Withdraw all diuretics and provide volume expansion with albumin for at least 2 days before confirming HRS diagnosis 2
• Exclude nephrotoxic drug exposure, shock, and structural kidney disease (proteinuria <0.5 g/day, no microhematuria <50 RBCs/HPF, normal renal ultrasound) 2

Monitoring Response to Treatment

• Check serum creatinine every 2-3 days to assess treatment response 1, 2
• Complete response = creatinine ≤1.5 mg/dL on two occasions 1
• Partial response = creatinine decrease ≥25% but still >1.5 mg/dL 2
• Monitor for complications: cardiac/intestinal ischemia, pulmonary edema, distal necrosis with terlipressin 2

Important Caveats and Pitfalls

• Discontinue albumin if anasarca develops (severe volume overload), but continue vasoconstrictors 3, 2
• The International Club of Ascites specifically recommends avoiding or discontinuing albumin in patients with anasarca, head trauma, or hemorrhagic shock 1
• Do not use octreotide as monotherapy—two studies definitively showed octreotide alone provides no benefit 1
• Even with treatment, recovery of renal function occurs in less than 50% of patients, and recovery may be partial even in full responders 4

Definitive Treatment

• Liver transplantation is the only curative treatment and should be expedited for all patients with type 1 HRS 1, 2
• Post-transplant survival rates are approximately 65% in type 1 HRS 1, 2
• Treatment of HRS before transplantation with vasoconstrictors may improve post-transplant outcomes 2
• The reduction in creatinine and MELD score after treatment should not delay transplantation decisions, as prognosis remains poor 2

Prevention Strategies

• For spontaneous bacterial peritonitis: Give albumin 1.5 g/kg at diagnosis, then 1 g/kg on day 3, which reduces HRS incidence from 30% to 10% and mortality from 29% to 10% 1, 2
• Patients with high bilirubin (≥4 mg/dL) or creatinine (≥1 mg/dL) are at higher risk and may benefit from albumin administration 1
• Norfloxacin 400 mg/day reduces HRS incidence in advanced cirrhosis 1, 2
• Pentoxifylline 400 mg three times daily prevents HRS in severe alcoholic hepatitis 1, 2