What is the management of hepatorenal syndrome?

Management of Hepatorenal Syndrome

Terlipressin plus albumin is the first-line treatment for hepatorenal syndrome, with liver transplantation being the definitive curative therapy. 1

Diagnostic Criteria

• HRS-AKI defined as >50% increase in serum creatinine from baseline
• No response to albumin administration
• Exclusion of other causes of renal failure
• Abdominal and renal ultrasound to confirm cirrhosis and rule out obstructive uropathy

First-Line Treatment Algorithm

1. Vasoconstrictor + Albumin Therapy

   • Terlipressin + Albumin (preferred first-line):

     • Terlipressin: Start at 1 mg IV every 4-6 hours
     • Increase to maximum 2 mg every 4-6 hours if serum creatinine doesn't decrease by ≥25% after 3 days
     • Albumin: 1 g/kg on day 1, followed by 20-40 g/day
     • Continue until serum creatinine improves or for up to 14 days
     • Response rate: 40-50% 1

   • Important limitation: Patients with serum creatinine >5 mg/dL are unlikely to benefit from terlipressin 2

2. Alternative Vasoconstrictors (if terlipressin unavailable):

   • Norepinephrine + albumin (ICU setting only)
   • Midodrine + octreotide + albumin:
     • Midodrine: Titrate up to 12.5 mg orally three times daily
     • Octreotide: 200 μg subcutaneously three times daily
     • Albumin: 10-20 g/day IV for up to 20 days 1

Monitoring During Treatment

• Serum creatinine, arterial pressure, urine volume, serum sodium
• Monitor for cardiovascular/ischemic complications (occur in ~12% of patients on terlipressin)
• Hold diuretics and beta-blockers until renal function improves
• Patients should be managed in ICU or semi-intensive care unit 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 (<5.0 mg/dL)
• Median time to response: 14 days (shorter with lower baseline creatinine) 1

Liver Transplantation

• Definitive curative treatment for both type 1 and type 2 HRS
• Survival rates approximately 65% in type 1 HRS 3
• Patients with HRS should be given priority for transplantation due to high mortality on waiting list
• Treatment of HRS before transplantation may improve post-transplant outcomes 3, 1

Other Interventions

1. Transjugular Intrahepatic Portosystemic Shunt (TIPS):

   • May improve renal function in selected patients
   • Limited applicability due to contraindications in many patients
   • Contraindicated in active infection, elevated bilirubin, recent hepatic encephalopathy 3, 1

2. Renal Replacement Therapy:

   • Consider for patients who don't respond to vasoconstrictor therapy
   • Can serve as bridge to liver transplantation
   • Continuous venous hemofiltration preferred due to less hemodynamic instability 3, 1

Prevention of HRS

• Norfloxacin (400 mg/day) reduces HRS incidence in advanced cirrhosis 3, 1
• Pentoxifylline (400 mg three times daily) may prevent HRS in severe alcoholic hepatitis 3, 1
• Treatment of spontaneous bacterial peritonitis with albumin plus antibiotics reduces HRS risk 1

Prognosis

• Untreated Type 1 HRS: median survival ~1 month
• All HRS patients: median survival ~3 months despite treatment
• Recurrence after withdrawal of terlipressin therapy is uncommon 1