In a patient with chronic liver disease and severe portal gastropathy but no esophageal varices, can non‑selective beta‑blockers be used for primary prophylaxis?

Beta-Blockers for Severe Portal Gastropathy Without Esophageal Varices

Yes, non-selective beta-blockers (NSBBs) should be initiated in patients with chronic liver disease and severe portal hypertensive gastropathy even in the absence of esophageal varices, as NSBBs reduce portal pressure and effectively manage bleeding from portal hypertensive gastropathy. 1, 2

Evidence-Based Rationale

Portal Hypertensive Gastropathy as an Indication

• The American Association for the Study of Liver Diseases explicitly recommends that bleeding from portal hypertensive gastropathy should be managed with portal hypertension-lowering measures, specifically NSBBs. 1

• NSBBs are recommended for chronic management of portal hypertensive gastropathy to reduce iron-deficiency anemia and improve quality of life in cirrhotic patients with chronic bleeding. 2

• Portal hypertensive gastropathy causes chronic bleeding leading to iron-deficiency anemia and significantly reduced quality of life, making NSBBs a therapeutic priority. 2

Mechanism Supporting Use Without Varices

• NSBBs reduce portal pressure by decreasing cardiac output (β1-receptor blockade) and causing splanchnic vasoconstriction (β2-receptor inhibition), which benefits all manifestations of portal hypertension, not just varices. 1, 3

• The European Association for the Study of the Liver (EASL) 2024 guidelines state that if clinically significant portal hypertension (CSPH) is present, NSBBs may be started unless contraindicated—this recommendation does not require the presence of varices. 4

When to Start Without Endoscopy

• If CSPH is highly probable based on clinical signs (such as severe portal gastropathy, splenomegaly, thrombocytopenia), NSBBs can be initiated empirically without first performing upper gastrointestinal endoscopy. 4

• The EASL 2024 guidelines note that NSBBs and endoscopic variceal ligation are both acceptable for primary prophylaxis, so if a patient has CSPH and can tolerate NSBBs, it is reasonable to start NSBBs without endoscopy. 4

• Liver stiffness measurement (LSM) >20 kPa and/or platelet count <150 × 10⁹/L indicate high probability of CSPH and warrant NSBB initiation. 4

Practical Dosing Protocol

Propranolol (First-Line)

• Start propranolol at 20 mg twice daily (immediate-release) or 80 mg once daily (long-acting formulation). 1

• Titrate every 2–3 days to a target dose of 160 mg daily; maximum allowable dose is 320 mg daily if tolerated. 1

• Alternative dosing: Start at 40 mg twice daily and titrate upward to 80 mg twice daily with goal of reducing resting heart rate by 25% or to 55 bpm. 2

Monitoring Targets

• Aim for ≥20% reduction in resting heart rate from baseline OR a resting heart rate of 55–60 beats per minute. 1

• Maintain systolic blood pressure >90 mmHg and mean arterial pressure >65 mmHg while on therapy. 1

• Check baseline heart rate and blood pressure before initiation and monitor at each dose adjustment. 2

Carvedilol Considerations

• Carvedilol is 2–4× more potent than propranolol in reducing portal pressure and achieves hemodynamic response in 50–75% of patients versus 46% with traditional NSBBs. 1

• However, carvedilol is associated with greater systemic hypotension and higher cost, limiting practicality in some settings. 1

• Target dose of carvedilol is 12.5 mg/day if chosen as alternative. 4

Absolute Contraindications

• Severe asthma or reactive airway disease 1

• Advanced atrioventricular (heart) block 1

• Decompensated heart failure 1

• Systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg 1

• Active variceal bleeding with hypotension (therapy should be paused until hemodynamic stability is achieved) 1

Critical Safety Considerations in Advanced Disease

Refractory Ascites Warning

• In patients with refractory ascites, NSBBs should be used with extreme caution or temporarily suspended if hypotension develops (systolic BP <90 mmHg or MAP <65 mmHg). 1

• As cirrhosis progresses and ascites becomes refractory, NSBBs can critically impair cardiac reserve and facilitate hemodynamic breakdown, imperiling renal perfusion. 5

• NSBB treatment should be carefully monitored in patients with refractory ascites, and other options for portal hypertension management should be considered if hemodynamic instability occurs. 5

Decompensated Cirrhosis

• The use of NSBBs in decompensated cirrhosis with ascites refractory to treatment remains controversial, with some studies suggesting potential harm in this specific population. 1

• High-dose statins in decompensated cirrhosis (Child-Pugh B or C) confer increased risk of severe adverse events including liver toxicity and rhabdomyolysis, though this pertains to statins, not beta-blockers. 4

Adjunctive Management

• Add iron supplementation to address iron-deficiency anemia from chronic blood loss due to portal hypertensive gastropathy. 2

• For active bleeding episodes, consider endoscopic argon plasma coagulation. 2

• For refractory cases despite NSBBs, TIPS or other portal pressure-lowering interventions may be necessary. 2

Additional Benefits Beyond Gastropathy

• NSBBs reduce the risk of first decompensation in patients with compensated cirrhosis and CSPH, even after successful etiological treatment (such as hepatitis C cure). 6

• NSBBs significantly reduce bacterial infection rates (hazard ratio 0.36) in patients with cirrhosis and portal hypertension. 6

• NSBBs prevent ascites development and death in compensated patients with CSPH, providing benefits beyond variceal bleeding prevention. 5