What is the management of hepatorenal syndrome?

Management of Hepatorenal Syndrome

First-Line Pharmacological Treatment

Terlipressin plus albumin is the first-line pharmacological treatment for hepatorenal syndrome type 1 (HRS-AKI), with an initial dose of 1 mg IV every 4-6 hours plus albumin 1 g/kg (maximum 100 g) on day 1, followed by 20-40 g/day of albumin. 1, 2

• If serum creatinine does not decrease by at least 25% after 3 days, increase terlipressin stepwise to a maximum of 2 mg every 4 hours 1
• Continue treatment until complete response (creatinine ≤1.5 mg/dL on two occasions) or for a maximum of 14 days 1, 3
• Terlipressin achieves reversal of HRS in 64-76% of patients, significantly superior to albumin alone 1, 4
• Important limitation: Patients with serum creatinine >5 mg/dL are unlikely to benefit from terlipressin 2

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm the diagnosis by meeting all criteria: 1, 5

• Cirrhosis with ascites and serum creatinine >1.5 mg/dL (or AKI stage 2-3)
• Perform diagnostic paracentesis to exclude spontaneous bacterial peritonitis, which precipitates HRS and requires specific antibiotic treatment plus albumin 1
• No improvement after 2 consecutive days of diuretic withdrawal and volume expansion with albumin (1 g/kg)
• Absence of shock, no recent nephrotoxic drug exposure
• Absence of structural kidney disease (proteinuria <0.5 g/day, no microhematuria <50 RBCs/HPF, normal renal ultrasound) 1

Alternative Vasoconstrictor Regimens

When Terlipressin is Unavailable

Norepinephrine plus albumin is the preferred alternative when terlipressin is unavailable and ICU access is available, with comparable efficacy (83% success rate in reversing HRS). 1, 5

• Start norepinephrine at 0.5 mg/hour IV, titrate every 4 hours by 0.5 mg/hour to maximum 3 mg/hour 5
• Goal: increase mean arterial pressure by 15 mmHg 1, 5
• Critical requirement: Requires central venous access and ICU-level monitoring; peripheral administration risks tissue necrosis 1
• Combine with albumin 20-40 g/day 1, 5
• Meta-analyses show no significant difference between terlipressin+albumin and norepinephrine+albumin in HRS reversal rates 5

Midodrine Plus Octreotide Plus Albumin

This combination is less effective than terlipressin or norepinephrine and should only be used when neither is available. 1, 3

• Midodrine: start 7.5 mg orally three times daily, titrate up to maximum 12.5 mg three times daily 1, 3
• Octreotide: 200 μg subcutaneously three times daily 1, 3
• Albumin: 10-20 g IV daily for up to 20 days 1, 3
• Advantage: Can be administered outside ICU and even at home 3
• Critical pitfall: Never use octreotide as monotherapy—it requires midodrine to be effective, as two studies definitively showed octreotide alone provides no benefit 3

Monitoring Treatment Response

Check serum creatinine every 2-3 days to assess response: 1, 3

• Complete response: Creatinine ≤1.5 mg/dL on two occasions
• Partial response: Creatinine decrease ≥25% but still >1.5 mg/dL
• Monitor for complications: cardiac/intestinal ischemia, pulmonary edema, distal necrosis with terlipressin 1
• Monitor mean arterial pressure, urine output, and serum sodium concentration 5

Definitive Treatment: Liver Transplantation

Liver transplantation is the only definitive treatment for HRS, with post-transplant survival rates of approximately 65% in type 1 HRS. 1, 3

• Expedited referral for transplantation is recommended for all patients with type 1 HRS 1
• Treatment with vasoconstrictors before transplantation may improve post-transplant outcomes 1
• Important consideration: Even if creatinine improves with vasoconstrictor therapy and MELD score decreases, this should not change the decision to proceed with liver transplantation, as prognosis after recovering from HRS remains poor 1

Prevention Strategies

In Spontaneous Bacterial Peritonitis

Albumin 1.5 g/kg at diagnosis of SBP, then 1 g/kg on day 3, reduces HRS incidence from 30% to 10% and mortality from 29% to 10%. 1, 3

• Highest benefit in patients with bilirubin ≥4 mg/dL or creatinine ≥1 mg/dL 3

In Advanced Cirrhosis

• Norfloxacin 400 mg/day reduces HRS incidence in advanced cirrhosis 1, 3
• Pentoxifylline 400 mg three times daily prevents HRS in severe alcoholic hepatitis 1, 3
• Avoid nephrotoxic drugs in all patients with advanced cirrhosis 1, 3

Adjunctive Therapies

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

TIPS may improve renal function and control of ascites in type 2 HRS, but evidence is limited to small uncontrolled studies. 1

Renal Replacement Therapy

Consider renal replacement therapy only as a bridge to liver transplantation in patients unresponsive to vasoconstrictor therapy. 1, 5

• Continuous venovenous hemofiltration/hemodialysis is preferred 1
• Very limited data on artificial liver support systems 1

Type 2 HRS Management

Type 2 HRS has a more stable course with moderate renal dysfunction: 3

• Same vasoconstrictor regimens can be used, though less urgently than type 1
• TIPS may be particularly beneficial for improving renal function and ascites control 1
• Liver transplantation remains definitive treatment 1