What is the management of Hepatorenal Syndrome (HRS)?

Management of Hepatorenal Syndrome (HRS)

Terlipressin plus albumin is the first-line pharmacological treatment for hepatorenal syndrome type 1 (HRS-AKI), with liver transplantation being the definitive treatment for both type 1 and type 2 HRS. 1

Diagnostic Criteria

• HRS is diagnosed by demonstrating a significant increase in serum creatinine (>133 μmol/L or 1.5 mg/dL) and excluding other causes of renal failure in cirrhotic patients 2
• Exclusion criteria include hypovolemia, shock, parenchymal renal diseases, and concomitant use of nephrotoxic drugs 2
• Two types of HRS exist: type 1 (rapid, progressive renal impairment with serum creatinine increasing ≥100% to >2.5 mg/dL in <2 weeks) and type 2 (stable or slowly progressive renal impairment) 2
• Repeated measurement of serum creatinine is crucial for early identification of HRS 2

Pathophysiology and Risk Factors

• Four key factors contribute to HRS pathogenesis: splanchnic vasodilation, activation of sympathetic nervous system and renin-angiotensin-aldosterone system, impaired cardiac function, and increased synthesis of vasoactive mediators 2
• Bacterial infections, particularly spontaneous bacterial peritonitis (SBP), are the most important risk factors for HRS development 2
• HRS develops in approximately 30% of patients who develop SBP 2
• The prognosis of untreated HRS is poor, with median survival of approximately 1 month for type 1 HRS 2

Treatment Algorithm

First-Line Therapy

• Vasoconstrictor therapy with terlipressin plus albumin is the first-line treatment for type 1 HRS 1, 2
• Terlipressin dosing: start at 1 mg IV every 4-6 hours, increase to maximum 2 mg/4-6 hours if serum creatinine does not decrease by at least 25% after 3 days 2, 1
• Continue treatment until serum creatinine decreases below 1.5 mg/dL (133 μmol/L) 2
• Treatment is effective in 40-50% of patients 2, 3
• Terlipressin increases renal blood flow by reducing portal hypertension and increasing effective arterial volume and mean arterial pressure 4
• For patients with partial response or no reduction in serum creatinine, discontinue treatment within 14 days 2

Alternative Vasoconstrictors

• In regions where terlipressin is unavailable, alternatives include:
  • Midodrine plus octreotide plus albumin (midodrine titrated up to 12.5 mg orally three times daily, octreotide 200 μg subcutaneously three times daily) 1
  • Norepinephrine plus albumin (requires ICU setting) 1, 2

Non-Pharmacological Therapies

• Renal replacement therapy may be useful in patients who do not respond to vasoconstrictor therapy and fulfill criteria for renal support 2
• Transjugular intrahepatic portosystemic shunt (TIPS) may improve renal function in some patients, but data are insufficient to support its routine use in type 1 HRS 2

Definitive Treatment

• Liver transplantation is the treatment of choice for both type 1 and type 2 HRS 2, 1
• Survival rates after transplantation are approximately 65% in type 1 HRS 2
• Patients with type 1 HRS should ideally be given priority for transplantation due to high mortality while on the waiting list 2
• Treatment of HRS before transplantation (with vasoconstrictors) may improve post-transplantation outcomes 2

Monitoring and Management

• Patients with type 1 HRS should be monitored carefully for urine output, fluid balance, arterial pressure, and standard vital signs 2
• Central venous pressure monitoring is ideal to help manage fluid balance 2
• Patients are generally better managed in an intensive care or semi-intensive care unit 2
• Response to therapy is characterized by progressive reduction in serum creatinine, increased arterial pressure, increased urine volume, and increased serum sodium concentration 2
• Median time to response is 14 days, with shorter response times in patients with lower baseline serum creatinine 2

Prevention of HRS

• Treatment of SBP with albumin infusion together with antibiotics reduces the risk of developing HRS and improves survival 2
• Norfloxacin (400 mg/day) can reduce the incidence of HRS in advanced cirrhosis 2, 1
• Pentoxifylline (400 mg three times daily) may prevent HRS development in patients with severe alcoholic hepatitis 2, 1

Important Considerations and Pitfalls

• The reduction in serum creatinine levels after treatment and related decrease in MELD score should not change the decision to perform liver transplantation, as prognosis after recovering from type 1 HRS remains poor 2
• Combined liver-kidney transplantation versus liver transplantation alone shows no advantage in HRS patients, except possibly for those under prolonged renal support therapy (>12 weeks) 2
• Renal replacement therapy should not be considered as first-line therapy for HRS 5
• Recovery of renal function can be achieved in less than 50% of patients with HRS after terlipressin use, and recovery may be only partial even in full responders 3