What is the management of hepatorenal syndrome?

Management of Hepatorenal Syndrome

Terlipressin plus albumin is the first-line pharmacological treatment for hepatorenal syndrome (HRS-AKI/Type 1 HRS), with liver transplantation being the only definitive cure. 1, 2, 3

Diagnostic Criteria

Before initiating treatment, HRS must be diagnosed by excluding other causes of acute kidney injury. The diagnosis requires: 1, 3

• Cirrhosis with ascites and serum creatinine >1.5 mg/dL 1
• No improvement after at least 2 days of diuretic withdrawal and volume expansion with albumin (1 g/kg/day up to maximum 100 g/day) 1
• Absence of shock 1
• No current or recent nephrotoxic drug exposure 1
• Absence of parenchymal kidney disease (proteinuria <0.5 g/day, no microhematuria <50 RBCs/HPF, normal renal ultrasound) 1
• Diagnostic paracentesis must be performed to rule out spontaneous bacterial peritonitis (SBP), which can precipitate HRS 2, 3

Classification

Type 1 HRS (HRS-AKI) is characterized by rapid progression with serum creatinine increasing ≥100% from baseline to >2.5 mg/dL in <2 weeks, with median survival of only 1 month if untreated. 1, 3

Type 2 HRS shows stable or slowly progressive renal impairment with better survival than Type 1. 1, 3

First-Line Pharmacological Treatment

Terlipressin Plus Albumin (Preferred)

Start with terlipressin 1 mg IV every 4-6 hours plus albumin. 1, 2, 3

Albumin dosing: 1 g/kg body weight on day 1 (maximum 100 g), followed by 20-40 g/day until complete response or maximum 14 days. 3

If serum creatinine does not decrease by at least 25% after 3 days, increase terlipressin stepwise to maximum 2 mg every 4 hours. 2, 3

Continue treatment until complete response or for maximum 14 days for partial response. 3

Important limitation: Patients with serum creatinine >5 mg/dL are unlikely to benefit from terlipressin. 4

Common pitfall: Terlipressin causes vasoconstriction and can lead to ischemic complications—monitor closely for signs of peripheral, cardiac, or mesenteric ischemia. 4 The drug increases blood pressure (mean arterial pressure increases by approximately 16 mmHg) and decreases heart rate (by approximately 11 beats/minute). 4

Alternative Pharmacological Treatments

Midodrine Plus Octreotide Plus Albumin

Use this regimen in regions where terlipressin is unavailable or as an alternative. 1, 2

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

Advantage: This combination can be administered outside the ICU and even at home. 2

Norepinephrine Plus Albumin

Norepinephrine plus albumin is an alternative option but requires ICU setting. 2, 3

Goal: Increase mean arterial pressure by 15 mmHg. 2

Success rate: 83% reported in pilot studies. 2

Definitive Treatment: Liver Transplantation

Liver transplantation is the only curative treatment for both Type 1 and Type 2 HRS. 1, 2, 3, 5

Patients with Type 1 HRS require expedited referral for transplantation. 2, 5

Post-transplant survival: Approximately 65% in Type 1 HRS patients. 2, 5

Critical point: Even if serum creatinine improves with vasoconstrictor therapy and MELD score decreases, this should not change the decision to proceed with liver transplantation, as long-term prognosis without transplant remains poor. 2

Treatment of HRS before transplantation with vasoconstrictors may improve post-transplant outcomes. 2

Adjunctive and Alternative Therapies

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

TIPS has been reported effective in small uncontrolled studies for Type 1 HRS and improves renal function in Type 2 HRS. 2, 5

However, evidence is limited (only 7 patients in one study for Type 1 HRS), and more data are needed before routine recommendation. 2

Renal Replacement Therapy

Continuous venovenous hemofiltration/hemodialysis may be considered as a bridge to liver transplantation in selected patients with Type 1 HRS. 2

Use RRT in patients who do not respond to vasoconstrictor therapy and fulfill criteria for renal support. 2

Prevention of HRS

In Spontaneous Bacterial Peritonitis

Albumin infusion with antibiotics is crucial for preventing HRS in SBP. 3

Dosing: 1.5 g/kg body weight at diagnosis, followed by 1 g/kg on day 3. 3

This reduces HRS Type 1 incidence from 30% to 10% and mortality from 29% to 10% compared to antibiotics alone. 3

Patients at highest risk (bilirubin ≥4 mg/dL or creatinine ≥1 mg/dL) benefit most from albumin administration. 3

Prophylactic Antibiotics

Norfloxacin 400 mg/day reduces HRS incidence in advanced cirrhosis. 2, 3, 5

In Alcoholic Hepatitis

Pentoxifylline 400 mg three times daily prevents HRS development in severe alcoholic hepatitis. 2, 3, 5

Avoid Nephrotoxic Drugs

Avoid nephrotoxic medications in patients with advanced cirrhosis. 3

Do not use hydroxyethyl starch or other artificial colloids—they are associated with harm in patients at risk of acute kidney injury and have no beneficial effect on circulatory function in SBP. 3

Monitoring and Supportive Care

Patients with Type 1 HRS should be managed in intensive or semi-intensive care units. 5

Monitor closely: 2, 5

• Urine output and fluid balance
• Arterial pressure and vital signs
• Central venous pressure (ideally) to assess response to treatment
• Signs of ischemic complications from vasoconstrictors

Nutritional support is essential: 5

• Daily energy intake: 35-40 kcal/kg
• Protein intake: 1.2-1.5 g/kg
• Small frequent meals (4-6 times daily including night snack)

Predictors of Treatment Response

Factors predicting poor response to terlipressin: 6

• High serum bilirubin
• High baseline creatinine
• Lack of blood pressure increase with treatment
• Presence of systemic inflammatory response syndrome

Response rate to terlipressin is only 40-50%, highlighting the need for early transplant evaluation. 6

Key Clinical Pitfalls to Avoid

Do not delay diagnosis: Early identification is critical—recent definitions using acute kidney injury staging help identify patients earlier. 3

Do not withhold albumin: Albumin is not interchangeable with crystalloids or artificial colloids in HRS treatment or SBP prevention. 3

Do not use albumin in: Head trauma (associated with harm), anasarca (severe volume overload), or hemorrhagic shock (prefer isotonic crystalloids). 3

Do not assume reversibility means cure: Even with creatinine improvement, patients need transplant evaluation as prognosis remains poor without transplantation. 2