How to manage patients with obstructive liver disease at risk for hepatorenal syndrome?

Management of Hepatorenal Syndrome in Obstructive Liver Disease

Early identification and aggressive management of hepatorenal syndrome (HRS) in patients with obstructive liver disease is essential, with terlipressin plus albumin as first-line therapy and liver transplantation as the definitive treatment. 1

Diagnostic Criteria

• HRS diagnosis requires excluding other causes of acute kidney injury in cirrhotic patients with:

  • Advanced cirrhosis with ascites
  • Serum creatinine >1.5 mg/dL
  • No improvement after at least 2 days of diuretic withdrawal and volume expansion with albumin (1 g/kg/day up to 100 g)
  • Absence of shock
  • No current/recent nephrotoxic drug exposure
  • Absence of parenchymal kidney disease (proteinuria <500 mg/day, no microhematuria, normal renal ultrasound) 2, 1

• Two types of HRS are recognized:

  • Type 1 HRS (HRS-AKI): Rapid, progressive renal impairment (serum creatinine increase ≥100% to >2.5 mg/dl in <2 weeks)
  • Type 2 HRS: Stable or less progressive renal impairment 2

Risk Factors and Prevention

• Bacterial infections, particularly spontaneous bacterial peritonitis (SBP), are the most important risk factors for HRS development 2
• Preventive measures include:
  • Albumin infusion with antibiotics when treating SBP to reduce HRS risk 2
  • Norfloxacin (400 mg/day) to reduce HRS incidence in advanced cirrhosis 1
  • Pentoxifylline (400 mg three times daily) to prevent HRS in severe alcoholic hepatitis 1
  • Diagnostic paracentesis to rule out SBP in patients with advanced cirrhosis and ascites 1

Treatment Algorithm

First-Line Pharmacological Treatment

• Terlipressin plus albumin is recommended as first-line therapy for type 1 HRS:
  • Initial dose: 1 mg IV every 4-6 hours
  • Increase dose stepwise to maximum 2 mg every 4 hours if serum creatinine doesn't decrease by ≥25% after 3 days 1

Alternative Pharmacological Options (where terlipressin is unavailable)

• Midodrine plus octreotide plus albumin:

  • Midodrine: Titrate up to 12.5 mg orally three times daily
  • Octreotide: 200 μg subcutaneously three times daily
  • Albumin: 10-20 g IV daily for up to 20 days 2, 1, 3

• Norepinephrine plus albumin (requires ICU setting):

  • Goal: Increase mean arterial pressure by 15 mmHg 1

Monitoring and Management

• Careful monitoring of:

  • Urine output
  • Fluid balance
  • Arterial pressure
  • Standard vital signs
  • Central venous pressure (ideally) to help manage fluid balance 2

• Patients with type 1 HRS are generally better managed in intensive or semi-intensive care units 2

Renal Replacement Therapy

• Hemodialysis or continuous venovenous hemofiltration may be considered as a bridge to liver transplantation in selected patients 2, 1
• Continuous venovenous hemofiltration causes less hypotension but requires continuous involvement of dialysis staff 2

Definitive Treatment

• Liver transplantation is the definitive treatment for both type 1 and type 2 HRS 1, 4
• Expedited referral for transplantation is recommended for patients with type 1 HRS 1
• Post-transplant survival rates are approximately 65% in type 1 HRS 1

Prognosis

• Untreated HRS has poor prognosis:
  • Average median survival of all HRS patients: approximately 3 months
  • Median survival of untreated type 1 HRS: approximately 1 month 2
• High MELD scores and type 1 HRS are associated with very poor prognosis 2
• Response to vasoconstrictor therapy is associated with improved survival 5
• Age, bilirubin levels, and creatinine increase after diagnostic volume expansion are independent predictors of mortality 5

Nutritional Management

• Adequate nutritional support is essential as malnutrition increases complications:
  • Daily energy intake: 35-40 kcal/kg
  • Protein intake: 1.2-1.5 g/kg
  • Avoid long-term protein restriction as it can induce protein catabolism, hepatic dysfunction, and sarcopenia 2
• Small frequent meals (4-6 times daily including night snack) improve long-term prognosis 2

Common Pitfalls and Considerations

• HRS diagnosis may be challenging in clinical practice - in one study, diagnostic criteria could not be completely fulfilled in one-third of cases 5
• Age is an independent predictor of response to vasoconstrictor therapy 5
• TIPS (transjugular intrahepatic portosystemic shunt) has shown effectiveness in small uncontrolled studies but requires more evidence 1
• Patients with at least two negative predictors (advanced age, high bilirubin, significant creatinine increase after volume expansion) have extremely high mortality rates (97%) 5