What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

Terlipressin plus albumin is the first-line treatment for hepatorenal syndrome, with a response rate of 40-50% of patients. 1 This combination therapy has been shown to effectively improve renal function and potentially improve short-term survival in patients with hepatorenal syndrome.

First-Line Treatment Approach

Terlipressin and Albumin Regimen

• Terlipressin dosing:

  • Start at 1 mg IV every 4-6 hours
  • Increase to maximum of 2 mg every 4-6 hours if serum creatinine does not decrease by at least 25% after 3 days of treatment
  • Continue until serum creatinine decreases below 1.5 mg/dL (133 μmol/L) 2

• Albumin dosing:

  • 1 g/kg on day 1
  • Followed by 20-40 g/day 2, 1

Monitoring During Treatment

• Monitor central venous pressure to manage fluid balance
• Avoid volume overload
• Patients should be managed in intensive care or semi-intensive care unit 2
• Monitor for cardiovascular or ischemic complications (occur in ~12% of patients) 2
• Monitor serum creatinine, arterial pressure, urine volume, and serum sodium concentration

Alternative Treatments

If terlipressin is unavailable or contraindicated:

1. Norepinephrine plus albumin (in ICU setting)

   • Norepinephrine: 0.5-3 mg/h as continuous infusion
   • Albumin: as per standard regimen 2, 1

2. Midodrine + octreotide + albumin

   • Midodrine: Start at 2.5-7.5 mg orally every 8 hours, titrate up to 12.5 mg three times daily
   • Octreotide: 100 μg subcutaneously every 8 hours, increase to 200 μg every 8 hours
   • Albumin: 10-20 g/day IV for up to 20 days 2, 1
   • Can be administered outside ICU and even at home 1

Predictors of Treatment Response

• Serum bilirubin <10 mg/dL before treatment
• Increase in mean arterial pressure >5 mm Hg at day 3 of treatment
• Lower baseline serum creatinine (especially <5.0 mg/dL) 1, 3
• Median time to response is 14 days, shorter in patients with lower baseline serum creatinine 2

Important Considerations

Mechanism of Action

Terlipressin is a synthetic vasopressin analogue that increases renal blood flow by:

• Reducing portal hypertension
• Reducing blood circulation in portal vessels
• Increasing effective arterial volume and mean arterial pressure 3

Limitations

• Patients with serum creatinine >5 mg/dL are unlikely to experience benefit 3
• Cardiovascular complications occur in approximately 12% of patients treated with terlipressin 2
• Most studies excluded patients with known severe cardiovascular conditions 2

Prevention of HRS

• Norfloxacin (400 mg/day) reduces HRS incidence in advanced cirrhosis 1
• Pentoxifylline (400 mg three times daily) may prevent HRS in severe alcoholic hepatitis 2, 1
• Treatment of spontaneous bacterial peritonitis with albumin plus antibiotics reduces risk of HRS development 1

Definitive Treatment

Liver transplantation is the only curative treatment for HRS 1, 4

• Expedited referral for transplantation should be considered for all patients with cirrhosis, ascites, and HRS
• Simultaneous liver-kidney transplantation may be considered for patients with significant kidney damage 1
• Continuous renal replacement therapy may be used as a bridge to liver transplantation in non-responders to vasoconstrictors 1

Prognosis

• Recurrence after withdrawal of terlipressin therapy is uncommon, and retreatment is generally effective 2
• Without treatment, median survival of Type 1 HRS is approximately 1 month 1
• Even with treatment, prognosis remains poor with a median survival of approximately 3 months for all HRS patients without liver transplantation 1