What is the treatment map for Hepatorenal Syndrome (HRS)?

From the Guidelines

The management of hepatorenal syndrome (HRS) primarily involves vasoconstrictors combined with albumin, with first-line treatment being terlipressin (0.5-2mg IV every 4-6 hours) plus albumin (20-40g/day IV), as recommended by the most recent study 1.

Key Considerations

• The treatment should be continued for 2-14 days until serum creatinine improves, with careful monitoring for potential side effects such as ischemic complications and pulmonary edema 1.
• If terlipressin is unavailable, norepinephrine (0.5-3mg/hour continuous infusion) with albumin is an alternative, as suggested by a meta-analysis comparing different vasoconstrictors in combination with albumin 1.
• For patients who cannot access these medications, midodrine (7.5-12.5mg orally three times daily) plus octreotide (100-200mcg subcutaneously three times daily) with albumin can be used, although this combination is less effective 1.
• Albumin should be given at 1g/kg on day 1, followed by 20-40g daily, to help improve systemic haemodynamics and counteract splanchnic vasodilation 1.

Supportive Care

• Careful fluid management, avoiding nephrotoxic drugs, treating precipitating factors like infections, and discontinuing diuretics are essential components of supportive care 1.
• Liver transplantation remains the definitive treatment for eligible patients with HRS, as it addresses the underlying liver dysfunction that drives the pathophysiology of this condition 1.

Monitoring and Treatment Adjustment

• Patients should be closely monitored for response to treatment, with therapy discontinued if creatinine remains at or above the pretreatment level over 4 days with the maximum tolerated doses of the vasoconstrictor 1.
• Recurrence may occur after treatment discontinuation and should be retreated, with consideration for urgent liver transplant evaluation given the high short-term mortality even in responders to vasoconstrictors 1.

From the FDA Drug Label

Terlipressin is thought to increase renal blood flow in patients with hepatorenal syndrome by reducing portal hypertension and blood circulation in portal vessels and increasing effective arterial volume and mean arterial pressure (MAP). For MAP, the estimated maximum effect was an increase of 16.2 mmHg.

The mean arterial pressure (MAP) for hepatorenal syndrome is increased by 16.2 mmHg with terlipressin administration 2.

• The increase in MAP is a result of terlipressin's mechanism of action, which includes reducing portal hypertension and increasing effective arterial volume.
• This increase in MAP is evident within 5 minutes after dosing and is maintained for at least 6 hours after dosing.

From the Research

Treatment Options for Hepatorenal Syndrome

• The mainstay of therapy for hepatorenal syndrome (HRS) is a vasoconstrictor (terlipressin or norepinephrine) combined with albumin, which achieves resolution of HRS in 40-50% of cases 3.
• Terlipressin plus albumin has been shown to be significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS 4.
• The combination of midodrine and octreotide with albumin is used as an alternative treatment for HRS, particularly in areas where terlipressin is not available 4, 5.
• Liver transplantation is the only option for patients failing to respond to medical therapies 3, 5.

Response to Treatment

• A complete response to treatment with vasoconstrictors and albumin was obtained in 30% of cases, and a partial response in 20% of cases 6.
• Age was found to be an independent predictor of response to treatment, with younger patients showing a better response 6.
• Survival was better in patients who responded to therapy, and mortality was strongly predicted by simple baseline variables such as age, bilirubin, and creatinine increase after diagnostic volume expansion 6.

Survival and Renal Function

• The therapeutic regimen of octreotide, midodrine, and albumin significantly improved short-term survival and renal function in both HRS type 1 and type 2 7.
• Transplant-free survival was higher in patients receiving octreotide, midodrine, and albumin compared to a historical cohort that did not receive this therapy 7.
• Renal function was significantly improved at 1 month in the treatment group compared to the control group 7.