What are the Baveno guidelines for primary prophylaxis of variceal bleeding in patients with cirrhosis?

Baveno Guidelines for Primary Prophylaxis of Variceal Bleeding in Cirrhosis

Primary Recommendation

Non-selective beta-blockers (NSBBs), specifically propranolol or nadolol, are the first-line treatment for primary prophylaxis of variceal bleeding in patients with high-risk varices, with endoscopic variceal ligation (EVL) reserved as an alternative when NSBBs are contraindicated or not tolerated. 1

Who Requires Primary Prophylaxis

Patients requiring prophylaxis include:

• All patients with large varices (grade 3) regardless of liver disease severity 1
• Patients with medium varices (grade 2) AND Child-Pugh class B or C disease 1
• Patients with small varices who have advanced liver disease (Child B/C) or red wale marks on endoscopy 1

The rationale is clear: decompensated patients (Child B/C) have a 72% prevalence of varices compared to 42% in Child A patients, and progression from small to large varices occurs in 22% at one year and 51% at three years in Child B/C patients 1.

First-Line Pharmacological Therapy: Propranolol Dosing

Starting dose: 40 mg twice daily, titrating to 80 mg twice daily as needed 1, 2

Therapeutic target: Reduce hepatic venous pressure gradient (HVPG) to <12 mmHg or achieve a 25% reduction from baseline, targeting a resting heart rate of 55-60 beats per minute 1, 2

Maximum doses:

• Without ascites: 320 mg/day 3
• With ascites: 160 mg/day (critical distinction for decompensated patients) 4, 2, 3
• With refractory ascites: Consider limiting to 80 mg/day for safety 4

Long-acting formulations: 80 or 160 mg once daily can be used to improve compliance once stable dosing is established 1, 2

Critical Monitoring Requirements

Blood pressure: Maintain systolic BP ≥90 mmHg throughout therapy 4, 3

Heart rate: Monitor at each visit to guide dose adjustments 2, 3

Renal function in decompensated disease: Monitor serum creatinine and sodium; reduce dose or discontinue if creatinine exceeds 1.5 mg/dL or sodium falls below 130 mmol/L 4

This monitoring is essential because NSBBs can critically impair cardiac reserve and renal perfusion in patients with refractory ascites, where systemic vasodilatation is severe and cardiodynamic equilibrium is fragile 5.

Alternative Therapies When NSBBs Cannot Be Used

First-line alternative: Endoscopic variceal ligation (EVL) 1, 2

Both NSBBs and EVL are equally effective in preventing first bleeding 1. However, NSBBs are preferred overall because EVL can cause severe bleeding from band ligation ulcers, requires repeat surveillance endoscopies for variceal recurrence, and does not reduce portal hypertension or prevent other cirrhosis complications 1.

Second-line alternative: Isosorbide mononitrate 20 mg twice daily (when neither propranolol nor EVL can be used) 1, 2

Surveillance Endoscopy Schedule

At diagnosis: All patients with cirrhosis should undergo screening endoscopy 1

No varices at baseline: Repeat endoscopy every 3 years 1

Small varices detected: Repeat endoscopy yearly 1

After decompensation: Patients without varices on previous endoscopy should have repeat endoscopy when decompensation develops, as the risk of developing varices increases with worsening portal hypertension (7-8% per year) 1

Secondary Prophylaxis (Prevention of Rebleeding)

Combination therapy with NSBBs plus EVL is mandatory for secondary prophylaxis, as this significantly decreases rebleeding compared to monotherapy 1

NSBBs are the cornerstone because adding NSBBs to EVL improves survival, while adding EVL to NSBBs does not affect mortality 1. HVPG-guided therapy may further improve outcomes when available 1.

Critical Pitfalls and Contraindications

Absolute contraindications to propranolol: Asthma, severe COPD, heart block, significant bradycardia, hypotension, decompensated heart failure 2

Never abruptly discontinue NSBBs: Abrupt cessation increases variceal bleeding risk and mortality; prefer dose reduction over complete discontinuation when possible 4, 3

Caution in refractory ascites: As cirrhosis progresses with refractory ascites, NSBBs can impair cardiac reserve and renal perfusion; careful monitoring or dose limitation to 80 mg/day is warranted 4, 5

Sclerotherapy is NOT recommended: Due to marked heterogeneity in trial results and potential for increased mortality, sclerotherapy cannot be recommended for primary prophylaxis 1

Why NSBBs Work Beyond Bleeding Prevention

NSBBs reduce portal pressure through splanchnic vasoconstriction (unopposed alpha-1 adrenergic effect) and reduced cardiac output (beta-blockade) 1. Additionally, they reduce bacterial translocation and may prevent other cirrhosis complications beyond variceal bleeding, providing mortality benefit that EVL alone does not achieve 1, 6.