Management of Hepatorenal Syndrome
Terlipressin plus albumin is the first-line pharmacological treatment for type 1 hepatorenal syndrome (HRS-AKI), while liver transplantation remains the definitive treatment for all types of HRS. 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, absence of shock, no current/recent nephrotoxic drug exposure, and absence of parenchymal kidney disease 1, 2
Diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis, which can precipitate HRS, in patients with advanced cirrhosis and ascites 1
Two types of HRS are recognized: Type 1 HRS (HRS-AKI) characterized by rapid, progressive renal impairment, and Type 2 HRS with a more chronic course 2
Treatment Algorithm
First-Line Therapy
- Terlipressin plus albumin is the first-line pharmacological treatment for type 1 HRS, with an initial dose of 1 mg IV every 4-6 hours 1, 2
- Dose should be increased stepwise to a maximum of 2 mg every 4 hours if serum creatinine doesn't decrease by at least 25% after 3 days 1
- Treatment should continue until complete response or maximum 14 days for partial response 2
- Terlipressin in intravenous continuous infusion is better tolerated than intravenous boluses and has the same efficacy 3
Alternative Therapies
In regions where terlipressin is unavailable, midodrine plus octreotide plus albumin is recommended as an alternative treatment for type 1 HRS 1, 2
Norepinephrine plus albumin is another treatment option for type 1 HRS, but requires an ICU setting, with a goal to increase mean arterial pressure by 15 mmHg 1, 2
Definitive Treatment
- Liver transplantation is the definitive treatment for both type 1 and type 2 HRS 1, 4, 2
- Expedited referral for transplantation is recommended for patients with type 1 HRS 1, 2
- Post-transplant survival rates are approximately 65% in type 1 HRS 1, 4
Bridging Therapies
- Continuous venovenous hemofiltration/hemodialysis may be considered as a bridge to liver transplantation in selected patients with type 1 HRS 1
- Transjugular intrahepatic portosystemic shunt (TIPS) has been reported to be effective in type 1 HRS in limited studies, but more evidence is needed 1
Prevention of HRS
- Albumin infusion with antibiotics when treating spontaneous bacterial peritonitis helps prevent HRS 2
- Norfloxacin (400 mg/day) is recommended to reduce the incidence of HRS in advanced cirrhosis 1, 2
- Pentoxifylline (400 mg three times daily) is recommended to prevent HRS development in patients with severe alcoholic hepatitis 1, 2
- Avoiding nephrotoxic drugs in patients with advanced cirrhosis is essential 2
Monitoring and Management
- Careful monitoring of urine output, fluid balance, arterial pressure, and standard vital signs is essential 4
- Patients with type 1 HRS are generally better managed in intensive or semi-intensive care units 4
Prognosis
- Untreated HRS has poor prognosis, with median survival of untreated type 1 HRS approximately 1 month 4
- High MELD scores and type 1 HRS are associated with very poor prognosis 4
- Serum bilirubin and creatinine levels, increase in blood pressure, and presence of systemic inflammatory response syndrome have been identified as predictors of response to treatment 3
Important Considerations and Pitfalls
- Terlipressin is effective in reversing HRS in only 40%-50% of patients 3, 5
- Differentiating HRS from acute tubular necrosis (ATN) is often challenging yet important because vasoconstrictors are not justified for the treatment of ATN 6
- HRS and ATN may be considered as a continuum rather than distinct entities 6
- Emerging biomarkers may help differentiate these conditions and provide prognostic information on kidney recovery after liver transplantation 6