Treatment of Esophageal Varices
For primary prevention of first variceal hemorrhage in patients with medium or large esophageal varices, nonselective beta-blockers (propranolol or nadolol) or endoscopic variceal ligation (EVL) are equally effective first-line options, with the choice based on patient tolerance, contraindications, and local expertise. 1, 2
Primary Prophylaxis (Prevention of First Bleed)
Risk Stratification and Treatment Indications
High-risk patients (Child-Pugh B/C or presence of red wale markings on endoscopy) with medium or large varices should receive either nonselective beta-blockers or EVL 1, 2. These patients have significantly elevated bleeding risk and mortality benefit from prophylaxis 1.
Lower-risk patients (Child-Pugh A without red signs) with medium or large varices should preferentially receive nonselective beta-blockers, with EVL reserved for those with contraindications, intolerance, or non-compliance to beta-blockers 1, 3.
Small varices with high-risk features (Child B/C or red wale marks) should be treated with nonselective beta-blockers 4. For small varices without high-risk features, beta-blockers can prevent progression to large varices, reducing the cumulative risk of variceal growth from 51% to 20% over follow-up 5.
Nonselective Beta-Blocker Therapy
Propranolol or nadolol are the preferred agents, reducing first variceal hemorrhage from 30% in untreated patients to 14% in treated patients, preventing one bleeding episode for every 10 patients treated 1. These agents work by decreasing cardiac output (β1 effect) and producing splanchnic vasoconstriction (β2 effect), thereby reducing portal blood flow 1.
Dosing: Propranolol is started at 40 mg once daily and titrated to the maximal tolerated dose, not simply to a 25% heart rate reduction, as heart rate reduction does not correlate with portal pressure reduction 1, 2. The goal is achieving maximal tolerated doses for optimal portal pressure reduction 1.
Monitoring: Once initiated, follow-up surveillance endoscopy is unnecessary for patients on beta-blockers 1. Regular monitoring of heart rate, blood pressure, and renal function is essential 2.
Endoscopic Variceal Ligation
EVL is equivalent to beta-blockers for preventing first variceal hemorrhage based on multiple large randomized trials 1, 3. EVL should be repeated every 1-2 weeks until obliteration, with first surveillance endoscopy 1-3 months after obliteration, then every 6-12 months to check for recurrence 1, 3.
Therapies to Avoid in Primary Prophylaxis
Do not use:
- Nitrates alone (isosorbide mononitrate) - associated with higher mortality in patients over 50 years by aggravating the vasodilatory state of cirrhosis 1, 2
- Combination beta-blocker plus nitrate - larger trials failed to confirm efficacy and showed more side effects 1
- Shunt therapy (TIPS or surgical shunts) - causes more encephalopathy and higher mortality 1, 2
- Endoscopic sclerotherapy - a VA trial was terminated early due to significantly higher mortality in the sclerotherapy group 1, 2
Secondary Prophylaxis (Prevention of Rebleeding)
The combination of EVL plus nonselective beta-blockers is the gold standard for preventing rebleeding after an initial variceal hemorrhage episode 1, 3. This combination is superior to either therapy alone, significantly reducing rebleeding rates with a trend toward decreased mortality 3.
If combination therapy cannot be performed, either nonselective beta-blockers or EVL alone is recommended 1.
TIPS placement should be reserved as rescue therapy for patients with primary treatment failure, not as first-line therapy, as it increases hepatic encephalopathy (35% vs 14%) despite lower rebleeding rates 1. There is no mortality benefit with TIPS compared to combination EVL plus beta-blockers 1.
Liver transplantation should be considered in patients with recurrent variceal rebleeding, and all patients with Child-Pugh score ≥7 or MELD ≥15 who survive variceal hemorrhage should be referred for transplant evaluation 1, 4.
Acute Variceal Bleeding
EVL should be performed emergently in all patients with acute esophageal variceal bleeding once hemodynamically stabilized and airway protected 3. EVL must be combined with vasoactive agents (octreotide, terlipressin, or somatostatin) and short-term antibiotic prophylaxis for optimal outcomes 3, 6.
Special Considerations for Gastric Varices
Gastroesophageal varices type 1 (GOV1) extending along the lesser curvature should follow the same treatment guidelines as esophageal varices, as they often disappear when esophageal varices are eradicated 2, 3.
For GOV2 and isolated gastric varices (IGV1) in the fundus, endoscopic cyanoacrylate injection may be more effective than EVL, though data for primary prophylaxis is limited 2.
Common Pitfalls
Underdosing beta-blockers is common - only 30.7% of patients receive optimal doses in real-world practice 7. Titrate to maximal tolerated dose, not just to heart rate targets 1, 2.
Premature discontinuation of surveillance after EVL - varices recur and require monitoring every 6-12 months indefinitely 1, 3.
Using selective beta-blockers (atenolol, metoprolol) - these are less effective and suboptimal for variceal prophylaxis 1.