Esophageal Varices
Table of Contents
Overview
Esophageal varices are dilated submucosal veins in the lower esophagus that develop as a consequence of portal hypertension, most commonly from cirrhosis.
They represent portosystemic collaterals — alternate routes formed when portal blood pressure rises and blood seeks lower-resistance pathways through the gastroesophageal junction veins.
Approximately 50% of all cirrhotic patients have varices at diagnosis; 30% will bleed within 2 years without prophylaxis.
Acute variceal hemorrhage (AVH) carries a 6-week mortality of approximately 20%, making this one of the most feared complications of chronic liver disease.
Portal Hypertension and Pathophysiology
Normal portal pressure gradient (HVPG — hepatic venous pressure gradient) is 1–5 mmHg.
- Clinically significant portal hypertension (CSPH): HVPG ≥10 mmHg — the threshold where varices begin to develop.
- Variceal bleeding risk increases sharply when HVPG >12 mmHg; risk of first bleed becomes negligible when HVPG drops below 12 mmHg with treatment.
- Baveno VII 2021 consensus defines CSPH as HVPG ≥10 mmHg or indirect surrogates: liver stiffness ≥25 kPa by transient elastography, or 20–25 kPa combined with platelet count <150,000.
The underlying mechanism involves two converging forces:
- Increased intrahepatic resistance — sinusoidal fibrosis and vascular remodeling from chronic liver injury.
- Splanchnic vasodilation — nitric oxide-mediated dilation of mesenteric vessels drives a hyperdynamic circulation that sustains and amplifies portal pressure.
Together these forces create the conditions for varices to form, enlarge, and ultimately rupture.
Causes and Risk Factors
Most Common Cause
Cirrhosis accounts for approximately 90% of cases. The leading underlying etiologies are:
- Alcohol-related liver disease
- Chronic hepatitis B or C
- Non-alcoholic steatohepatitis (NASH)/metabolic dysfunction-associated steatotic liver disease (MASLD)
Less Common Non-Cirrhotic Causes
- Portal vein thrombosis — extrahepatic portal hypertension, often in younger patients
- Schistosomiasis — a major cause in endemic regions of Africa, South America, and Southeast Asia
- Budd-Chiari syndrome — hepatic vein outflow obstruction
- Nodular regenerative hyperplasia — sinusoidal portal hypertension without classic cirrhosis
Risk Factors for Variceal Bleeding
- Varix size — large varices (>5 mm) carry the highest risk
- Red wale markings on endoscopy — longitudinal red streaks indicating areas of thin, tensed variceal wall
- Child-Pugh class C (decompensated cirrhosis)
- Active alcohol use — raises portal pressure acutely and impairs hepatic synthetic function
Baveno VII Consensus and Diagnosis
The Baveno VII 2021 international consensus workshop updated the criteria for non-invasive diagnosis and management stratification of portal hypertension.
EGD (esophagogastroduodenoscopy) remains the gold standard for diagnosing and grading varices.
Screening Recommendations
- EGD has traditionally been done at the time of cirrhosis diagnosis.
- Re-screening intervals vary by compensated vs. decompensated status and response to treatment.
- Non-invasive rule-out ("Baveno VI rule"): under this rule, people with liver stiffness <20 kPa AND platelet count >150,000 have a very low probability of high-risk varices, and the rule spares them a screening EGD.
Variceal Grading
- Small: <5 mm, minimally tortuous
- Medium: intermediate size
- Large: ≥5 mm, occupy more than one-third of the esophageal lumen
Additional Diagnostic Tools
- Capsule endoscopy — endorsed by Baveno VII as an alternative to EGD for screening in selected patients who decline or cannot tolerate standard endoscopy.
- Transient elastography — liver stiffness measurement used as a non-invasive surrogate for HVPG to stratify risk without direct pressure measurement.
Primary Prophylaxis
The goal of primary prophylaxis is to prevent the first variceal bleed in patients who have never bled.
Non-Selective Beta-Blockers (NSBBs)
- Propranolol (dose usually titrated to lower the resting heart rate by 25% or to 55 beats per minute) or nadolol — older agents, well-established efficacy.
- Carvedilol 6.25 mg/day — preferred for CSPH with varices per Baveno VII; provides greater portal pressure reduction than propranolol or nadolol and also reduces hepatic inflammation via alpha-1 blockade.
- Caution: propranolol and nadolol are contraindicated or used cautiously in refractory ascites (may reduce renal perfusion); carvedilol carries the same caution.
Endoscopic Variceal Ligation (EVL)
- Preferred for medium/large varices or when NSBBs are intolerated or contraindicated.
- EGD is repeated every 2–4 weeks until varices are eradicated, then for surveillance every 3–6 months.
Combined Therapy
NSBB + EVL combined is not superior to either alone for primary prophylaxis (unlike secondary prophylaxis, where combination is standard of care).
Acute Variceal Hemorrhage
Acute variceal hemorrhage (AVH) is a medical emergency with approximately 20% 6-week mortality even with optimal treatment.
Resuscitation Principles
- Restrictive transfusion strategy: target hemoglobin 7–8 g/dL — overtransfusion raises portal pressure and increases rebleeding risk.
- Airway protection: elective intubation before endoscopy is used in encephalopathic or actively vomiting patients.
Early Pharmacotherapy (Started Before Endoscopy)
Initiating vasoactive therapy before endoscopy reduces active bleeding and improves outcomes:
- Octreotide: 50 mcg intravenous (IV) bolus, then 50 mcg/hr infusion for 3–5 days (splanchnic vasoconstriction reducing portal inflow).
- Terlipressin: 2 mg intravenous every 4–6 hours — reduces portal pressure via V1 receptor-mediated splanchnic vasoconstriction; the only vasoactive agent with demonstrated mortality benefit in randomized controlled trials.
- Antibiotics: intravenous ceftriaxone 1 g/day for 5–7 days — a 1999 meta-analysis found that short-term antibiotic prophylaxis in cirrhosis with gastrointestinal bleeding reduces infections and increases short-term survival; in a 2006 Gastroenterology randomized controlled trial (RCT) of 111 patients with advanced cirrhosis and hemorrhage, ceftriaxone prevented infections better than oral norfloxacin (proven or possible infections 11% vs 33%), with no difference in hospital mortality.
Endoscopy Within 12 Hours
- EVL is preferred over endoscopic sclerotherapy — equivalent hemostasis with fewer complications (strictures, ulcers).
- For gastric varices (type 2): cyanoacrylate glue injection or a transjugular intrahepatic portosystemic shunt (TIPS) is preferred over EVL.
Salvage Therapy (Failure to Control or Early Rebleeding Within 5 Days)
- TIPS — highly effective rescue therapy; see dedicated section below.
- Balloon tamponade (Sengstaken-Blakemore tube or Linton-Nachlas) — bridge only, maximum 24 hours; significant complication risk (aspiration, esophageal necrosis).
- Self-expanding esophageal metal stents — emerging bridge therapy with lower complication profile than balloon tamponade.
TIPS Procedure
The transjugular intrahepatic portosystemic shunt (TIPS) creates a direct channel between the portal vein and hepatic vein via a covered metal stent deployed through the liver parenchyma, bypassing the high-resistance sinusoidal circulation.
Hemodynamic Effect
Portal pressure gradient typically falls from 18–22 mmHg to <12 mmHg after TIPS — below the threshold for variceal bleeding.
Early TIPS (High-Risk Patients)
Early TIPS within 72 hours of AVH (ideally within 24 hours) in high-risk patients — Child-Pugh B with active bleeding or Child-Pugh C <14 — dramatically reduces rebleeding and improves survival compared to standard NSBB + EVL. This was established by Garcia-Pagan et al. in the landmark 2010 NEJM trial.
Technical Considerations
- Covered TIPS stents lined with expanded polytetrafluoroethylene (PTFE) are standard — superior long-term patency compared to bare metal stents.
- Also used for refractory ascites and hepatic hydrothorax.
Complications
- Hepatic encephalopathy — occurs in 20–35% of patients post-TIPS; results from portal blood bypassing hepatic detoxification and reaching systemic circulation directly.
- Shunt dysfunction or occlusion
- Hemolysis (shear stress on red cells through the stent)
- Cardiac volume overload (portal decompression increases venous return)
Secondary Prophylaxis
The goal of secondary prophylaxis is to prevent rebleeding after the index hemorrhage. Without treatment, rebleeding occurs in 60–70% of patients within 1–2 years.
Combination Therapy — Standard of Care
NSBB + EVL combined is superior to either alone for secondary prophylaxis and is recommended by all major guidelines (American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), Baveno VII).
- NSBB: propranolol or nadolol titrated to a heart rate of 55–60 beats per minute; carvedilol if tolerated.
- EVL: repeated every 2–4 weeks until variceal eradication, then 3–6 month surveillance endoscopy.
Rebleeding Despite Combination Therapy
For people who rebleed despite NSBB + EVL, TIPS is the standard next step; it reduces rebleeding to <10% per year.
Liver Transplantation
Transplantation ultimately addresses the underlying cause of portal hypertension. TIPS serves as a bridge to transplant in eligible patients, maintaining hemostasis while they await organ allocation.
Key Research Papers
- de Franchis R et al.; Baveno VII Faculty. "Renewing consensus in portal hypertension." J Hepatol. 2022;76(4):959–974. — PubMed PMID: 35120736
- Garcia-Tsao G, Abraldes JG et al. "Portal hypertensive bleeding in cirrhosis: AASLD practice guidance 2017." Hepatology. 2017;65(1):310–335. — PubMed PMID: 27786365
- Villanueva C et al. "Transfusion strategies for acute upper gastrointestinal bleeding." N Engl J Med. 2013;368(1):11–21. — PubMed PMID: 23281973
- Bernard B et al. "Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding." Hepatology. 1999;29(6):1655–1661. — PubMed PMID: 10347104
- Lo GH et al. "A prospective randomized trial of sclerotherapy versus ligation in the management of bleeding esophageal varices." Hepatology. 1995;22(2):466–471. — PubMed PMID: 7635414
- Garcia-Pagan JC et al. "Early use of TIPS in patients with cirrhosis and variceal bleeding." N Engl J Med. 2010;362(25):2370–2379. — PubMed PMID: 20573925
- Tripathi D et al. "UK guidelines on the management of variceal haemorrhage in cirrhotic patients." Gut. 2015;64(11):1680–1704. — PubMed PMID: 25887380
- Fernández J, Ruiz del Arbol L, Gómez C, et al. "Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage." Gastroenterology. 2006;131(4):1049–1056. — PubMed PMID: 17030175
- Lo GH et al. "Endoscopic variceal ligation plus nadolol and sucralfate compared with ligation alone for the prevention of variceal rebleeding." Hepatology. 2000;32(3):461–465. — PubMed PMID: 10960435
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