What medication is used to minimize the risk of complications from portal hypertension in patients with liver cirrhosis?

From the Guidelines

Non-selective beta-blockers (NSBBs), such as propranolol and nadolol, are the primary drugs given to minimize the risk from portal hypertension in patients with liver cirrhosis. The choice of NSBBs is based on their ability to reduce portal pressure by decreasing cardiac output and causing splanchnic vasoconstriction, thereby reducing blood flow to the portal system 1. This helps prevent complications like variceal bleeding, which is a life-threatening consequence of portal hypertension.

Key Considerations

• The typical starting dose for propranolol is 20-40 mg twice daily, with gradual titration based on heart rate response (aiming for a 25% reduction from baseline or a heart rate of 55-60 beats per minute) 1.
• Nadolol is usually started at 20-40 mg once daily.
• Carvedilol, an NSBB with intrinsic anti-alpha-1 receptor activity, has been associated with a greater reduction in portal pressure than traditional NSBBs, but its use may be limited in decompensated patients due to its potential to cause systemic haemodynamic depressive effects 1.
• Regular monitoring of blood pressure and heart rate is essential during treatment, and patients should be advised not to stop these medications abruptly as this can lead to a rebound increase in portal pressure.

Special Considerations in Advanced Cirrhosis

• In patients with refractory ascites, the use of NSBBs should be based on a critical risk/benefit evaluation, and parameters such as severe hyponatraemia, low mean arterial pressure or cardiac output, and increasing SCr should be considered to identify more vulnerable patients 1.
• The BAVENO VI consensus proposes that in patients with refractory ascites and certain conditions (e.g., systolic blood pressure <90 mmHg, SCr >1.5 mg/dl, or hyponatraemia <130 mmol/L), the NSBB dose should be reduced or even temporarily discontinued 1.

Alternatives and Combination Therapy

• In patients who cannot tolerate beta-blockers, alternatives include carvedilol (starting at 6.25 mg daily) or combination therapy with isosorbide mononitrate.
• Combination therapy with NSBBs and endoscopic band ligation (EBL) is recommended for secondary prophylaxis of variceal hemorrhage, as it significantly decreases the probability of rebleeding compared to monotherapy 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). The drug given to minimize the risk from portal hypertensions among patients with liver cirrhosis is terlipressin (IV), as it reduces portal hypertension and blood circulation in portal vessels 2.

• Key benefits: reducing portal hypertension, increasing effective arterial volume and mean arterial pressure (MAP)
• Target population: patients with hepatorenal syndrome type 1 (HRS-1) and liver cirrhosis

From the Research

Portal Hypertension Treatment

To minimize the risk from portal hypertensions among patients with liver cirrhosis, the following drugs are used:

• Non-selective beta-blockers (NSBBs) such as propranolol and carvedilol 3, 4, 5, 6, 7

Mechanism of Action

NSBBs work by:

• Reducing cardiac output 5
• Reducing splanchnic vasodilatation 5
• Lowering portal pressure 3, 6

Benefits and Limitations

The use of NSBBs has several benefits, including:

• Reducing the risk of variceal bleeding 3, 4
• Preventing liver decompensation in patients with compensated cirrhosis 4
• Reducing bacterial translocation and spontaneous bacterial peritonitis in cirrhosis 6 However, NSBBs also have some limitations and potential harmful effects, such as:
• Systemic hypotension and renal failure 5
• Potential harmful effects in patients with refractory ascites 3, 6