What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

Terlipressin plus albumin is the first-line pharmacological treatment for hepatorenal syndrome, with an initial dose of 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 only definitive cure. 1, 2

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm the diagnosis by ensuring all criteria are met: 1

• 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, which precipitates HRS and requires specific antibiotic treatment plus albumin 1, 3

First-Line Pharmacological Treatment

Terlipressin Plus Albumin (Preferred)

This is the gold standard pharmacological therapy with the strongest evidence base: 1, 2

• Initial dosing: Terlipressin 1 mg IV every 4-6 hours plus albumin 1 g/kg (maximum 100 g) on day 1, then albumin 20-40 g/day 1, 3
• Dose escalation: If serum creatinine doesn't decrease by ≥25% after 3 days, increase terlipressin stepwise to maximum 2 mg every 4 hours 1
• Duration: Continue until complete response (creatinine ≤1.5 mg/dL on two occasions) or maximum 14 days 1, 3
• Efficacy: Achieves HRS reversal in 64-76% of patients, significantly superior to albumin alone 1
• Limitation: Patients with serum creatinine >5 mg/dL are unlikely to benefit 2

Critical monitoring requirements: 1

• Check serum creatinine every 2-3 days
• Monitor for cardiac/intestinal ischemia, pulmonary edema, and distal necrosis
• Ideally manage in ICU or semi-ICU setting with central venous pressure monitoring

Alternative Pharmacological Options

Midodrine Plus Octreotide Plus Albumin

Use this combination when terlipressin is unavailable or contraindicated: 1, 3

• Midodrine: Start 7.5 mg orally three times daily, titrate up to maximum 12.5 mg three times daily 1, 3
• Octreotide: 100-200 μg subcutaneously three times daily 1, 3
• Albumin: 10-20 g IV daily for up to 20 days 1, 3
• Advantage: Can be administered outside ICU and even at home 3
• Important caveat: Never use octreotide as monotherapy—it requires midodrine to be effective, as two studies definitively showed octreotide alone provides no benefit 3

Norepinephrine Plus Albumin

This is an effective alternative but requires ICU admission: 1, 3

• Dosing: 0.5-3.0 mg/hour IV, titrated to increase mean arterial pressure by 15 mmHg 1
• Albumin: 20-40 g/day 1
• Efficacy: 83% success rate in reversing type 1 HRS in pilot studies 1
• Critical requirement: Requires central venous access—attempting peripheral administration risks tissue necrosis 1
• Monitoring: Continuous hemodynamic monitoring in ICU setting mandatory 1

Definitive Treatment: Liver Transplantation

Liver transplantation is the only curative treatment for HRS: 1, 3

• Expedited referral is mandatory for all patients with type 1 HRS (HRS-AKI) 1, 4
• Post-transplant survival rates are approximately 65% in type 1 HRS 1, 4
• Treatment with vasoconstrictors before transplantation may improve post-transplant outcomes 1
• Important consideration: Even if serum creatinine improves with vasoconstrictor therapy and MELD score decreases, this should NOT change the decision to proceed with transplantation, as prognosis after recovering from HRS remains poor 1

Adjunctive and Bridge Therapies

Renal Replacement Therapy

• Consider only as a bridge to liver transplantation in patients unresponsive to vasoconstrictors 1
• Not recommended as first-line therapy 1
• Continuous venovenous hemofiltration/hemodialysis may be used in selected patients 1

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

• Has shown effectiveness in improving renal function and controlling ascites in type 2 HRS 1
• Limited evidence for type 1 HRS (only uncontrolled study of 7 patients) 1
• Consider in appropriate candidates, particularly for type 2 HRS 1

Prevention Strategies

Prevention is critical and should be implemented in high-risk patients: 1, 3, 4

During Spontaneous Bacterial Peritonitis

• Albumin 1.5 g/kg at diagnosis, then 1 g/kg on day 3 reduces HRS incidence from 30% to 10% and mortality from 29% to 10% 1, 3
• Patients with bilirubin ≥4 mg/dL or creatinine ≥1 mg/dL are at highest risk and benefit most 3

Prophylactic Measures

• Norfloxacin 400 mg/day reduces HRS incidence in advanced cirrhosis 1, 4
• Pentoxifylline 400 mg three times daily prevents HRS in severe alcoholic hepatitis 1, 4
• Avoid nephrotoxic drugs in all patients with advanced cirrhosis 1

Common Pitfalls to Avoid

• Never use hydroxyethyl starch or other artificial colloids instead of albumin—they are associated with harm in patients at risk of AKI 3
• Do not delay liver transplant evaluation even if patient responds to vasoconstrictors 1
• Discontinue albumin if anasarca develops, but continue vasoconstrictors 1
• Do not use octreotide without midodrine—it is ineffective as monotherapy 3
• Recognize that less than 50% of patients achieve complete response to terlipressin, and early mortality remains very high without transplantation 5, 6