What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

Terlipressin plus albumin is the first-line pharmacological treatment for hepatorenal syndrome, with liver transplantation being the only definitive cure. 1

Initial Pharmacological Management

First-Line Therapy (Where Available)

• Terlipressin plus albumin should be initiated immediately with terlipressin 1 mg IV every 4-6 hours, escalating stepwise to a maximum of 2 mg every 4 hours if serum creatinine doesn't decrease by at least 25% after 3 days 1
• Albumin should be administered at 1 g/kg on day 1 (maximum 100g) followed by 20-40 g/day 2
• This combination achieves response rates of approximately 35-45% 2

Alternative Regimens (When Terlipressin Unavailable)

In regions without terlipressin access, use midodrine plus octreotide plus albumin as the alternative regimen: 1

• Midodrine: titrate up to 12.5 mg orally three times daily 1
• Octreotide: 200 μg subcutaneously three times daily 1
• Albumin: 10-20 g IV daily for up to 20 days 1
• This combination can be administered outside the ICU and even at home 1

Norepinephrine plus albumin is another effective option but requires ICU monitoring: 1

• Start at 0.5-3.0 mg/h (or 5 mcg/minute) with goal to increase mean arterial pressure by 15 mmHg 2, 3
• Success rates of 83% have been reported, though recent real-world data shows 45% response when used as rescue therapy 1, 3
• Achieving a MAP increase of ≥10 mm Hg above baseline is associated with greater probability of response 3

Sequential Treatment Algorithm

For patients who fail initial midodrine-octreotide therapy, escalate to norepinephrine rather than abandoning vasoconstrictor treatment: 3

• Only 28% of patients respond to midodrine-octreotide alone 3
• Of non-responders, 45% achieve response when escalated to norepinephrine 3
• Responders to norepinephrine experience significantly improved 90-day transplant-free survival (88% versus 27%) 3

Management of Volume Overload Complications

When anasarca develops during treatment, discontinue albumin but continue vasoconstrictors: 2

• Albumin has limited utility once severe peripheral edema develops, indicating significant fluid overload 2
• Vasoconstrictors (terlipressin, norepinephrine, or octreotide-midodrine) should be maintained even after albumin discontinuation 2
• Implement sodium restriction (<2g/day) and consider diuretic therapy for volume management 2
• Fluid restriction to <1000 mL/day should only be implemented if serum sodium <125 mEq/L 2

Definitive Treatment

Liver transplantation is the definitive treatment and should be expedited for all patients with hepatorenal syndrome: 1

• Post-transplant survival rates are approximately 65% in type 1 HRS 1
• Treatment with vasoconstrictors before transplantation may improve post-transplant outcomes 1
• Even if serum creatinine improves with vasoconstrictor therapy and MELD score decreases, this should not change the decision to proceed with transplantation, as prognosis remains poor 1

Adjunctive Therapies

TIPS may be considered in selected patients with lower MELD scores: 2

• TIPS improves renal function and ascites control in type 2 HRS 1
• Limited data exists for type 1 HRS, with only small uncontrolled studies showing benefit 1

Renal replacement therapy should be considered as a bridge to transplantation when: 2

• Worsening kidney function despite vasoconstrictor therapy 2
• Fluid overload persists despite diuretic therapy 2
• Problematic acid-base status develops 2
• Continuous venovenous hemofiltration/hemodialysis is preferred over intermittent hemodialysis 1

Prevention Strategies

Implement preventive measures in high-risk cirrhotic patients: 1, 4

• Norfloxacin 400 mg/day reduces HRS incidence in advanced cirrhosis 1, 4
• Pentoxifylline 400 mg three times daily prevents HRS in severe alcoholic hepatitis 1, 4
• Albumin infusion with antibiotics when treating spontaneous bacterial peritonitis 4
• Always perform diagnostic paracentesis to rule out SBP, which can precipitate HRS 1

Critical Monitoring Parameters

Monitor these parameters to assess treatment response: 4

• Daily weights and fluid balance 2
• Serum creatinine (goal: ≥25% reduction after 3 days) 1
• Mean arterial pressure (goal: increase of 10-15 mmHg) 1, 3
• Central venous pressure ideally should be monitored 1
• Urine output and standard vital signs 4

Important Pitfalls to Avoid

Do not abandon vasoconstrictor therapy prematurely: 2

• Continue vasoconstrictors even when albumin must be discontinued due to volume overload 2
• Consider sequential escalation to more potent agents rather than stopping treatment 3

Recognize poor prognostic indicators that warrant urgent transplant evaluation: 5

• Age, bilirubin level, and creatinine increase after diagnostic volume expansion independently predict mortality 5
• Mortality rate approaches 97% in patients with at least two negative predictors 5
• Development of anasarca indicates poor prognosis and should prompt urgent transplant consideration 2
• Untreated type 1 HRS has a median survival of approximately 1 month 4

Be aware that diagnostic criteria cannot always be completely fulfilled in real-world practice: 5

• In 36% of cases, HRS is presumed because not all diagnostic criteria can be fulfilled 5
• In 8% of cases, HRS is superimposed on organic nephropathy 5
• Treatment should not be withheld solely based on inability to meet all diagnostic criteria if clinical suspicion is high 5