Oesophageal Varices

1. Clinical Overview

Summary

Oesophageal varices are dilated portosystemic venous collaterals in the submucosa of the lower oesophagus that develop as a direct consequence of portal hypertension, most commonly secondary to liver cirrhosis. They represent one of the most serious complications of chronic liver disease, with variceal haemorrhage constituting a life-threatening gastroenterological emergency. [1,2]

Approximately 50% of patients with cirrhosis have varices at the time of diagnosis, with the prevalence increasing to 60-80% in those with decompensated cirrhosis. The annual incidence of new varix formation is 5-8% in patients without varices at baseline screening. [1,3] Varices progress from small to large at a rate of 10-12% per year, with large varices (>5mm) carrying the highest bleeding risk. [4]

The annual risk of first variceal bleed ranges from 5% for small varices to 15% for large varices with high-risk stigmata. [1] Once bleeding occurs, mortality at 6 weeks approaches 15-20% despite modern management strategies, with mortality being highest in those with advanced liver disease (Child-Pugh C class). [5] The risk of rebleeding within 1-2 years without secondary prophylaxis is approximately 60%, with most episodes occurring within the first 6 weeks. [6]

Management is structured around three key clinical scenarios:

1. Primary Prophylaxis: Prevention of first bleed in patients with medium/large varices using non-selective beta-blockers (NSBB) such as propranolol or carvedilol, or endoscopic variceal ligation (EVL). [1,7]

2. Acute Variceal Bleeding: Emergency management combining resuscitation, vasoactive drugs (terlipressin or octreotide), prophylactic antibiotics (ceftriaxone), and emergency endoscopy with band ligation within 12 hours. [8,9]

3. Secondary Prophylaxis: Prevention of rebleeding using combination therapy with NSBB plus EVL, which reduces rebleeding risk to 20-30% annually. [1,10]

Transjugular intrahepatic portosystemic shunt (TIPSS) serves as rescue therapy for refractory bleeding and is increasingly used as early intervention in high-risk patients (Child-Pugh C score 10-13 or Child-Pugh B with active bleeding at endoscopy). [11,12]

Clinical Pearls

"The Rule of 50s": 50% of cirrhotics have varices, 50% of large varices will bleed over 2 years, and 50% of first bleeds occur within the first year of varix development.

"Triple Therapy Saves Lives": The acute variceal bleeding triad is Vasoactive drugs (Terlipressin) + Emergency EVL + Antibiotics (Ceftriaxone). All three components reduce mortality. [8,9]

"Antibiotics Are Not Optional": Prophylactic antibiotics in acute variceal bleeding reduce bacterial infections by 35% and mortality by 9%, making them a mandatory component of care. [13]

"HVPG >20 mmHg Means High Mortality": Hepatic venous pressure gradient above 20 mmHg predicts treatment failure and increased mortality in acute bleeding. [14]

"Carvedilol Over Propranolol": Baveno VII consensus suggests carvedilol as the preferred NSBB for primary prophylaxis due to superior portal pressure reduction. [1,7]

"Early TIPSS for High-Risk": Consider pre-emptive TIPSS within 72 hours for Child-Pugh C (10-13) or Child-Pugh B with active bleeding—reduces treatment failure and mortality. [12]

"Over-Resuscitation Kills": Target Hb 7-8 g/dL. Aggressive transfusion to >9 g/dL increases portal pressure and rebleeding risk. [15]

---

2. Epidemiology

Prevalence and Natural History

Aetiology of Portal Hypertension

Cirrhotic Causes (>90% in Western Countries)

Non-Cirrhotic Causes

Risk Factors for Variceal Bleeding

Patient-Related Factors

Endoscopic High-Risk Stigmata

• Red Wale Marks: Longitudinal dilated subepithelial veins
• Cherry-Red Spots: Flat discrete red marks
• Haematocystic Spots: Raised blood-filled blebs ("blood blisters")
• White Nipple Sign: Fibrin plug at previous rupture site
• Diffuse Redness: Generalised erythema over varix surface

Global Distribution

• Western Countries: Cirrhosis from alcohol and NAFLD predominates
• Sub-Saharan Africa / Middle East: Schistosomiasis remains important cause
• East Asia: Hepatitis B-related cirrhosis historically dominant
• Southeast Asia: Hepatitis C and alcohol significant contributors

---

3. Pathophysiology

Portal Hypertension: The Fundamental Abnormality

Portal hypertension is defined as a portal venous pressure >5 mmHg (normal 1-5 mmHg). The hepatic venous pressure gradient (HVPG), measured as the difference between wedged and free hepatic venous pressures, provides an indirect but reliable assessment of portal pressure. [14]

HVPG Thresholds

Mechanism of Portal Hypertension in Cirrhosis

Portal hypertension in cirrhosis results from two synergistic mechanisms: [1,17]

1. Increased Intrahepatic Vascular Resistance (Structural and Functional)

Structural Component (60-70%):

• Fibrosis and Nodular Regeneration: Distortion of hepatic architecture compresses sinusoids and hepatic venules
• Sinusoidal Remodelling: Capillarisation of sinusoids with loss of fenestrations
• Vascular Occlusion: Collagen deposition in Space of Disse reduces sinusoidal compliance
• Angiogenesis: Abnormal vessel formation with shunting

Functional Component (30-40%):

• Hepatic Stellate Cell Activation: Myofibroblast transformation increases contractility
• Endothelial Dysfunction: Decreased nitric oxide (NO) bioavailability increases vasoconstriction
• Increased Endothelin-1, Angiotensin II, Noradrenaline: Promote sinusoidal constriction
• Decreased eNOS Activity: Further reduces NO-mediated vasodilation

2. Increased Portal Venous Inflow (Hyperdynamic Circulation)

• Splanchnic Vasodilation: Mediated by increased NO, carbon monoxide, and endocannabinoids in mesenteric circulation
• Increased Cardiac Output: Compensatory response to peripheral vasodilation
• Decreased Systemic Vascular Resistance: Creates hyperdynamic circulatory state
• Increased Splenic Blood Flow: Splenomegaly and congestion

This creates a vicious cycle: portal hypertension → splanchnic vasodilation → increased portal inflow → worsening portal hypertension.

Development of Portosystemic Collaterals (Varices)

As portal pressure exceeds 10-12 mmHg, blood seeks alternative routes to return to the systemic circulation through portosystemic anastomoses (sites where portal and systemic venous systems communicate naturally). [1]

Anatomical Sites of Portosystemic Collaterals

Oesophageal Varix Formation: Precise Anatomy

Gastro-oesophageal Venous Drainage:

1. Portal System: Left gastric vein (coronary vein) drains gastric fundus and distal oesophagus → Portal vein
2. Systemic System: Oesophageal veins drain into azygos/hemiazygos system → Superior vena cava
3. Zone of Communication: Distal 2-5 cm of oesophagus and gastric cardia

When portal pressure rises:

• Blood flows retrograde up the left gastric vein
• Enters submucosal oesophageal venous plexus
• Forms tortuous, dilated varices
• Drains via perforating veins through oesophageal wall into paraesophageal and azygos veins

Gastric Varices: Sarin Classification

Gastric varices differ in anatomy and behaviour from oesophageal varices [27]:

Variceal Rupture: Laplace's Law

Variceal rupture occurs when wall tension exceeds wall strength. Wall tension is governed by Laplace's Law: [1]

T = (P × r) / w

Where:

• T = Wall tension
• P = Transmural pressure (portal pressure - intra-oesophageal pressure)
• r = Variceal radius (size)
• w = Wall thickness

Clinical Implications:

• Large varices (increased radius) have higher wall tension
• High portal pressure directly increases wall tension
• Thin variceal wall (measured by endoscopic stigmata) reduces resistance to rupture
• Red signs indicate areas of maximal wall thinning and highest rupture risk

Precipitating Factors for Rupture:

• Sudden increase in intra-abdominal pressure (straining, coughing, vomiting)
• Alcohol binge (acute hepatotoxicity and coagulopathy)
• Bacterial infection (increases portal pressure via inflammatory mediators)
• Medication non-adherence (stopping beta-blockers)

Molecular Mechanisms of Portal Pressure

Nitric Oxide Imbalance

Intrahepatic (Cirrhotic Liver):

• ↓ eNOS Expression: Reduced NO production in sinusoidal endothelium
• ↑ Arginase Activity: Decreased arginine substrate for NO synthesis
• ↑ Asymmetric Dimethylarginine (ADMA): Endogenous eNOS inhibitor accumulates
• Result: Sinusoidal vasoconstriction

Splanchnic (Mesenteric Circulation):

• ↑ eNOS Expression: Excessive NO in mesenteric vessels
• ↑ iNOS Induction: Inflammatory NO production
• Result: Splanchnic vasodilation and increased portal inflow

Vasoactive Mediator Imbalance

Haemodynamic Consequences of Variceal Bleeding

Acute variceal haemorrhage triggers a cascade of deleterious effects:

1. Hypovolaemia: Reduced effective circulating volume
2. Sympathetic Activation: Increased catecholamines raise portal pressure
3. Increased Portal Inflow: Reflex splanchnic vasodilation
4. Further Bleeding: Positive feedback loop
5. Hepatic Ischaemia: Reduced hepatic perfusion worsens liver function
6. Bacterial Translocation: Intestinal oedema and ischaemia allow bacterial/endotoxin translocation
7. Systemic Inflammation: Sepsis-like syndrome even without documented infection
8. Hepatic Encephalopathy: Protein load from blood + hepatic insufficiency + reduced clearance of ammonia
9. Hepatorenal Syndrome: Renal hypoperfusion and vasoconstriction

---

4. Classification Systems

Variceal Size Classification

Child-Pugh Score

The Child-Pugh score assesses severity of cirrhosis and predicts prognosis in variceal bleeding: [19]

Classification:

• Child-Pugh A (5-6 points): Compensated cirrhosis; 1-year survival 100%, operative mortality 10%
• Child-Pugh B (7-9 points): Significant dysfunction; 1-year survival 80%, operative mortality 30%
• Child-Pugh C (10-15 points): Decompensated cirrhosis; 1-year survival 45%, operative mortality 80%

Clinical Relevance in Variceal Bleeding:

• Child-Pugh C has 3-fold higher bleeding risk than Child-Pugh A
• 6-week mortality after first bleed: Class A (0-5%), Class B (10-15%), Class C (20-30%)

MELD Score (Model for End-Stage Liver Disease)

MELD = 3.78×ln[bilirubin mg/dL] + 11.2×ln[INR] + 9.57×ln[creatinine mg/dL] + 6.43

• More objective than Child-Pugh (no subjective variables)
• Used for liver transplant prioritisation
• MELD >18 correlates with high mortality in acute variceal bleeding

Rockall Score for Upper GI Bleeding

While developed for all upper GI bleeding, useful for risk stratification in variceal bleeding: [20]

Interpretation:

• Score 0-2: Low risk (mortality less than 5%)
• Score 3-5: Moderate risk (mortality 5-10%)
• Score ≥6: High risk (mortality >10%)

Note: Varices typically score high due to "liver failure" component (2 points) and "blood in upper GI tract" (2 points).

Endoscopic Classification of Active Bleeding

---

5. Clinical Presentation

Asymptomatic Phase

Most patients with varices are asymptomatic until bleeding occurs. Varices are typically discovered during:

• Screening endoscopy at cirrhosis diagnosis (recommended per Baveno VII) [1]
• Incidental finding during endoscopy for other indications
• Imaging (CT/MRI showing oesophageal varices or gastric varices)

Acute Variceal Bleeding: Classical Presentation

Cardinal Symptoms

Signs of Hypovolaemic Shock

Compensated Shock (Blood loss less than 750 mL):

• Mild tachycardia (HR 90-100 bpm)
• Cool peripheries
• Delayed capillary refill (>2 seconds)
• Normal blood pressure (initially)

Moderate Shock (Blood loss 750-1500 mL):

• Tachycardia (HR 100-120 bpm)
• Tachypnoea (RR 20-30/min)
• Hypotension (SBP 80-100 mmHg)
• Oliguria (less than 0.5 mL/kg/hr)
• Anxiety, confusion

Severe Shock (Blood loss >1500 mL):

• Severe tachycardia (HR >120 bpm)
• Profound hypotension (SBP less than 80 mmHg)
• Altered consciousness
• Anuria
• Skin mottling, cyanosis

Features Distinguishing Variceal from Non-Variceal Bleeding

Stigmata of Chronic Liver Disease

Physical findings suggesting underlying cirrhosis:

Skin:

• Spider Naevi: Vascular lesions with central arteriole (upper body distribution)
• Palmar Erythema: Reddening of thenar and hypothenar eminences
• Jaundice: Yellow discolouration of skin and sclera
• Caput Medusae: Dilated periumbilical veins radiating from umbilicus
• Bruising: Easy bruising from coagulopathy and thrombocytopenia

Hands:

• Clubbing: Bulbous enlargement of fingertips
• Leuconychia: White nails (hypoalbuminaemia)
• Dupuytren's Contracture: Palmar fascia thickening (alcohol-related)

Abdomen:

• Ascites: Shifting dullness, fluid thrill
• Hepatosplenomegaly: Palpable liver edge (may be small and shrunken in advanced disease); splenomegaly from portal hypertension
• Dilated Abdominal Veins: Visible collateral circulation

Endocrine:

• Gynaecomastia: Breast tissue enlargement in males
• Testicular Atrophy: Hypogonadism
• Loss of Body Hair: Reduced secondary sexual characteristics

Other:

• Hepatic Fetor: Sweet, musty breath odour (from mercaptans)
• Asterixis: "Flapping tremor" (indicates encephalopathy)
• Muscle Wasting: Sarcopenia from malnutrition and catabolism

Precipitants and Triggers of Variceal Bleeding

• Spontaneous: Most common (no identifiable trigger)
• Infection: Bacterial translocation and inflammatory mediators increase portal pressure
• Alcohol Binge: Acute hepatotoxicity, coagulopathy, increased portal pressure
• Non-Adherence to Beta-Blockers: Loss of portal pressure reduction
• Constipation/Straining: Increased intra-abdominal pressure
• NSAIDs/Anticoagulants: Worsen bleeding risk
• Hepatocellular Carcinoma: Can thrombose portal vein or increase portal pressure

Complications Presenting During or After Bleeding

Hepatic Encephalopathy

Precipitated by:

• Protein Load: Blood in GI tract (100 mL blood = 15-20g protein) → ammonia production
• Hypovolaemia: Reduced cerebral perfusion
• Infection: Often coexists
• Constipation: Impaired ammonia excretion
• Hypokalaemia: From diuretics or bleeding

Grading:

• Grade 1: Altered sleep pattern, mild confusion
• Grade 2: Lethargy, disorientation, asterixis
• Grade 3: Somnolence, marked confusion, incomprehensible speech
• Grade 4: Coma, unresponsive

Hepatorenal Syndrome

Type 1 (Acute): Rapidly progressive renal failure (doubling of creatinine to >221 μmol/L in less than 2 weeks) Type 2 (Chronic): Slower, moderate renal impairment

Triggered by:

• Hypovolaemia from bleeding
• Splanchnic vasodilation and renal vasoconstriction
• RAAS and sympathetic activation
• Inflammatory cytokines

Spontaneous Bacterial Peritonitis (SBP)

30-40% of cirrhotic patients with GI bleeding develop bacterial infections, most commonly SBP. [13]

Mechanism:

• Bacterial translocation from ischaemic gut
• Impaired immune function (cirrhosis)
• Ascites as culture medium

Prophylactic antibiotics (ceftriaxone) reduce infection risk and mortality.

Aspiration Pneumonia

Risk factors:

• Massive haematemesis
• Altered consciousness (encephalopathy)
• Absent gag reflex
• Supine positioning

Prevention: Early airway protection (intubation) if massive bleeding or Grade 3-4 encephalopathy.

---

6. Investigations

Immediate (Emergency Department / Resuscitation)

Special Consideration—Urea:Creatinine Ratio:

• Urea is elevated from protein digestion of blood in GI tract
• Urea:Cr ratio >100 (in mg/dL) or >30 (in SI units) suggests upper GI bleeding
• Useful to differentiate upper vs lower GI source

Endoscopy (Oesophagogastroduodenoscopy, OGD)

Gold standard for diagnosis and treatment of variceal bleeding. [8]

Indications and Timing

Endoscopic Findings

Oesophageal Varices:

• Location: Lower oesophagus (distal 5-10 cm)
• Appearance: Serpentine, blue submucosal columns
• Size grading: Small (less than 5mm), Medium (5-10mm), Large (>10mm)
• High-risk stigmata: Red wale marks, cherry-red spots, haematocystic spots, white nipple sign

Active Bleeding:

• Spurting: Pulsatile jet of blood from varix (F2)
• Oozing: Continuous slow bleeding (F1)
• Recent bleeding: Adherent clot, fibrin plug

Gastric Varices:

• GOV1: Extension along lesser curve
• GOV2: Extension into fundus
• IGV1: Isolated fundal varices
• IGV2: Isolated varices elsewhere

Portal Hypertensive Gastropathy (PHG):

• Mild: Mosaic-like pattern (snake-skin appearance)
• Severe: Discrete red spots, diffuse redness, friability
• Can be source of chronic blood loss

Cross-Sectional Imaging

CT Abdomen/Pelvis with IV Contrast

Indications:

• Assess underlying liver parenchyma (cirrhosis, nodularity, atrophy/hypertrophy)
• Identify hepatocellular carcinoma (HCC)
• Evaluate portal vein patency (thrombosis)
• Detect portosystemic collaterals
• Assess spleen size
• Identify ascites

Findings in Portal Hypertension:

• Oesophageal/gastric varices (enhancing tubular structures)
• Splenomegaly (spleen >13 cm)
• Portosystemic collaterals (splenorenal, paraumbilical, gastrorenal)
• Portal vein dilatation (>13 mm) or thrombosis
• Ascites
• Cirrhotic morphology (nodular liver, caudate hypertrophy, right lobe atrophy)

MRI/MRCP

• Better soft tissue contrast than CT
• Useful for liver lesion characterisation (HCC vs benign)
• MRCP evaluates biliary tree (PSC, strictures)
• No radiation exposure

Doppler Ultrasound Liver

Non-invasive first-line imaging for portal vein assessment.

Findings:

• Portal vein diameter: >13 mm suggests portal hypertension
• Portal vein flow: Direction (hepatopetal vs hepatofugal), velocity (less than 16 cm/s suggests portal hypertension)
• Portal vein thrombosis: Echogenic material in lumen, absent flow
• Liver echotexture: Coarse, heterogeneous (cirrhosis)
• Splenomegaly: >12-13 cm
• Ascites: Anechoic fluid in peritoneum
• Portosystemic collaterals: Coronary vein (left gastric), splenorenal shunt

Hepatic Venous Pressure Gradient (HVPG)

Invasive measurement of portal pressure via transjugular catheterisation of hepatic vein. [14]

Procedure:

1. Catheter inserted via internal jugular vein
2. Advanced into hepatic vein (usually right)
3. Wedged Hepatic Venous Pressure (WHVP): Balloon inflated to occlude hepatic vein (reflects sinusoidal pressure)
4. Free Hepatic Venous Pressure (FHVP): Balloon deflated (reflects IVC pressure)
5. HVPG = WHVP - FHVP

Clinical Use:

• Research tool and specialist centres
• Prognostic value: HVPG response to beta-blockers predicts bleeding risk
• Threshold for vasoactive therapy: HVPG reduction >20% or to less than 12 mmHg reduces bleeding
• Pre-TIPSS assessment

Limitations:

• Invasive, requires specialist expertise
• Only accurate in sinusoidal portal hypertension (cirrhosis)
• Not accurate in presinusoidal (schistosomiasis) or prehepatic (portal vein thrombosis) causes

Transient Elastography (FibroScan)

Non-invasive assessment of liver stiffness (fibrosis).

• Liver Stiffness Measurement (LSM): Predicts degree of fibrosis
  • less than 7 kPa: No/minimal fibrosis
  • 7-10 kPa: Moderate fibrosis
  • 10-14 kPa: Severe fibrosis
  • >14 kPa: Cirrhosis
  • >20-25 kPa: High risk of portal hypertension and varices

Baveno VII Criteria: LSM less than 20 kPa + Platelets >150 → Low risk of varices, can avoid screening endoscopy [1]

Laboratory Investigations for Underlying Cause

---

7. Management

Primary Prophylaxis (Prevention of First Bleed)

Goal: Prevent first variceal haemorrhage in patients with medium or large varices.

Indications [1]

Non-Selective Beta-Blockers (NSBB) [1,7]

Mechanism:

• Beta-1 blockade: Reduces cardiac output → reduced portal inflow
• Beta-2 blockade: Unopposed alpha-adrenergic activity → splanchnic vasoconstriction → reduced portal inflow
• Net effect: Reduces HVPG by 10-20%

Choice of NSBB: [1,7]

Target:

• Heart rate 55-60 bpm OR 25% reduction from baseline
• Systolic BP maintained >90 mmHg

Contraindications:

• Asthma, severe COPD
• Decompensated heart failure
• Advanced heart block
• Severe hypotension

Adverse Effects:

• Fatigue, dizziness
• Bradycardia
• Hypotension
• Sexual dysfunction
• Bronchospasm (avoid in asthma)

Evidence: Carvedilol superior to propranolol in recent trials for reducing HVPG and preventing variceal bleeding. [7]

Endoscopic Variceal Ligation (EVL)

Technique:

• Elastic bands placed circumferentially around varices
• Varices strangulate, necrose, slough off
• Healing with fibrosis and obliteration
• Repeat sessions every 2-4 weeks until varices eradicated (typically 2-4 sessions)

Efficacy: Equivalent to NSBB for primary prophylaxis. [1]

Advantages:

• No systemic side effects
• Effective when NSBB contraindicated or not tolerated

Disadvantages:

• Requires multiple sessions
• Risk of procedure complications (bleeding, ulceration, stricture)
• Varices can recur (requires surveillance)

Complications:

• Post-banding ulceration and bleeding (5-10%)
• Transient dysphagia
• Oesophageal stricture (rare, less than 5%)
• Perforation (very rare)

NSBB vs EVL: Which to Choose? [1]

Baveno VII Recommendations: [1,21,29]

• Either NSBB or EVL acceptable for primary prophylaxis
• NSBB preferred for most patients (systemic benefits, easier adherence)
• EVL preferred if NSBB contraindicated or not tolerated
• Combination (NSBB + EVL) NOT recommended for primary prophylaxis (no additional benefit, higher adverse events)

---

Acute Variceal Bleeding Management

Algorithm: Simultaneous resuscitation, pharmacotherapy, and endoscopic therapy. [8,9]

Step 1: Initial Resuscitation and Stabilisation

ABCDE Approach:

A - Airway:

• High-risk patients: Massive haematemesis, Grade 3-4 encephalopathy, haemodynamic instability
• Consider early intubation for airway protection (aspiration risk)
• Position patient in left lateral position if conscious

B - Breathing:

• High-flow oxygen (target SpO2 94-98%)
• Monitor respiratory rate

C - Circulation:

• Large bore IV access x 2 (14-16G cannulae)
• Bloods: FBC, coagulation, U&E, LFT, lactate, VBG, group & save, crossmatch 4-6 units
• Fluid resuscitation: Crystalloid (0.9% NaCl or Hartmann's)
  • "Avoid over-resuscitation: Target SBP 90-100 mmHg (permissive hypotension until haemostasis)"
  • Over-resuscitation increases portal pressure and rebleeding risk [15]

D - Disability:

• Assess GCS, signs of encephalopathy
• Check blood glucose

E - Exposure:

• Examine for stigmata of chronic liver disease
• Assess for ascites, hepatosplenomegaly

Step 2: Blood Product Resuscitation [15]

Target Haemoglobin: 7-8 g/dL (restrictive strategy)

Evidence: Liberal transfusion (target Hb >9 g/dL) increases portal pressure, rebleeding, and mortality vs restrictive (Hb 7-8 g/dL). [15]

Step 3: Pharmacotherapy (Start IMMEDIATELY, Before Endoscopy)

Vasoactive Drugs [9]

Mechanism: Splanchnic vasoconstriction → reduced portal inflow → reduced portal pressure and variceal bleeding

Evidence: Vasoactive drugs reduce bleeding, transfusion requirements, and 5-day treatment failure by ~40%. Start before endoscopy and continue for 2-5 days. [9]

Antibiotic Prophylaxis [13]

Rationale:

• 30-40% of cirrhotic patients with GI bleeding develop bacterial infections (SBP, UTI, pneumonia) [13,21]
• Bacterial translocation from gut during bleeding
• Infections increase rebleeding risk and mortality
• Prophylactic antibiotics reduce infections by 35% and mortality by 9% [13]

Regimen:

Baveno VII Recommendation: Ceftriaxone 1g IV OD for all patients with acute variceal bleeding (high prevalence of quinolone-resistant organisms). [1,13,21,28]

Proton Pump Inhibitors (PPIs)

Role: Controversial in pure variceal bleeding (varices not acid-related)

• Commonly used to prevent ulcer-related bleeding (peptic ulcers coexist in 10-20%)
• No evidence of harm; reasonable to give (e.g., omeprazole 40 mg IV BD)

Step 4: Emergency Endoscopy (Within 12 Hours) [8]

Timing: Within 12 hours of presentation (ideally 6-12 hours) after resuscitation

Pre-Endoscopy Checklist:

• Vasoactive drug started (terlipressin/octreotide)
• Antibiotics given (ceftriaxone)
• Adequate resuscitation (SBP >90 mmHg)
• Coagulopathy corrected (INR less than 1.8, Plt >50)
• Airway protection if needed (intubation for massive bleeding or encephalopathy)
• Informed consent (if possible)

Endoscopic Variceal Ligation (EVL) - First-Line [8]

Technique:

• Multi-band ligation device
• Varices suctioned into cap and banded sequentially
• Start at gastro-oesophageal junction, work proximally
• Aim to band all visible varices (typically 4-8 bands)

Efficacy:

• Controls bleeding in 80-90% of cases
• Reduces rebleeding vs sclerotherapy
• Fewer complications than sclerotherapy

Sclerotherapy - Alternative

Technique:

• Inject sclerosant (ethanolamine, sodium tetradecyl sulfate) intravariceal or paravariceal
• Causes thrombosis and fibrosis

Indications:

• EVL not feasible (massive bleeding obscuring view, technical difficulty)
• Gastric varices (if cyanoacrylate not available)

Complications:

• Ulceration, stricture, perforation, mediastinitis (higher than EVL)
• EVL preferred when feasible

Gastric Varices - Cyanoacrylate Injection [18]

Indications: GOV2 (fundal extension) or IGV1 (isolated fundal varices)

Technique:

• Inject N-butyl-2-cyanoacrylate (glue) intravariceal
• Rapid polymerisation causes variceal obliteration

Efficacy: Superior to EVL for gastric varices (EVL has high failure rate)

Complications: Embolisation (systemic, pulmonary), needle impaction, infection

Step 5: Refractory Bleeding (Endoscopic Failure)

Definition: Failure to control bleeding after 2 endoscopic attempts within 24 hours

Balloon Tamponade (Sengstaken-Blakemore Tube or Minnesota Tube)

Mechanism: Inflate oesophageal and/or gastric balloon to compress varices mechanically

Indications: Temporary bridge to definitive therapy (TIPSS) when endoscopy fails

Procedure:

1. Intubation strongly recommended (aspiration risk)
2. Insert tube orogastrically
3. Inflate gastric balloon first (250-300 mL), pull back to gastro-oesophageal junction
4. If bleeding continues, inflate oesophageal balloon (30-40 mmHg)
5. Maximum duration: 24 hours (risk of oesophageal necrosis)

Complications:

• Aspiration pneumonia (30-40%)
• Oesophageal rupture/perforation
• Pressure necrosis

Success Rate: Controls bleeding in 80-90%, but high rebleeding rate (50%) after deflation

Transjugular Intrahepatic Portosystemic Shunt (TIPSS) [11,12]

Mechanism: Creates low-resistance channel between hepatic vein and portal vein, reducing portal pressure [21,24,25]

Indications:

1. Refractory bleeding: Failure of pharmacological + endoscopic therapy
2. Early (pre-emptive) TIPSS in high-risk patients:
   • Child-Pugh C (score 10-13) OR
   • Child-Pugh B with active bleeding at endoscopy [12]

Procedure:

• Percutaneous transjugular approach
• Catheter advanced from hepatic vein into portal vein
• Tract dilated and stented (typically covered stent to reduce stenosis)

Efficacy:

• Controls refractory bleeding in greater than 95%
• Early TIPSS (within 72 hours) in high-risk patients reduces treatment failure by 50% and mortality by 30% [12,31]
• TIPSS with variceal embolization: Further reduces rebleeding in patients with post-TIPSS portal pressure gradient greater than 12 mmHg [25]

Complications:

• Hepatic encephalopathy: 20-30% (mechanism: shunting of portal blood bypasses hepatic ammonia clearance)
• Heart failure: Increased venous return
• Stent stenosis/occlusion: 20-30% with bare stents; less than 10% with covered stents
• Haemolysis: From shear stress

Contraindications:

• Child-Pugh C score greater than 13 (poor survival, consider transplant) [21]
• MELD greater than 18-24 (relative)
• Severe hepatic encephalopathy [32]
• Right heart failure
• Severe pulmonary hypertension

Self-Expanding Metal Stent (SEMS)

Indication: Temporary measure for refractory bleeding when TIPSS not immediately available

Technique: Fully covered self-expanding oesophageal stent placed endoscopically to compress varices

Duration: Maximum 7 days, then remove (or migrate to TIPSS)

Efficacy: Controls bleeding in 85-90% as bridge to TIPSS

---

Secondary Prophylaxis (Prevention of Rebleeding)

Goal: Prevent recurrent variceal bleeding after index bleed controlled.

Rationale: 60% rebleeding risk within 1-2 years without prophylaxis; rebleeding carries 20-30% mortality. [6]

Combination Therapy: NSBB + EVL (First-Line) [1,10]

Evidence: Combination therapy superior to either alone, reducing rebleeding to ~20-30% at 1 year. [10]

Regimen:

1. NSBB: Start propranolol or carvedilol (same dosing as primary prophylaxis)
2. EVL: Repeat sessions every 2-4 weeks until varices obliterated (typically 2-4 sessions)
3. Surveillance OGD: 3 months post-eradication, then 6-12 monthly

If Varices Recur: Repeat EVL sessions

TIPSS for Recurrent Bleeding

Indications:

• Rebleeding despite optimal NSBB + EVL
• Intolerance/contraindication to NSBB
• Patient preference (avoid repeated endoscopy)

Efficacy: Highly effective at preventing rebleeding (less than 10% rebleed rate)

Trade-off: Higher encephalopathy risk (20-30%)

Liver Transplantation

Definitive treatment for portal hypertension and underlying cirrhosis.

Indications for Transplant Assessment:

• Child-Pugh C cirrhosis
• MELD >15
• Recurrent variceal bleeding despite therapy
• Hepatocellular carcinoma within Milan criteria
• Decompensated cirrhosis (ascites, encephalopathy, jaundice)

Timing: Early referral to transplant centre essential

---

Surveillance and Long-Term Management

Screening Endoscopy in Cirrhosis [1]

Baveno VII Non-Invasive Criteria to Avoid Screening OGD: [1,21,23]

• Liver stiffness less than 20 kPa AND Platelets >150 x10⁹/L → Very low risk of varices, can defer OGD

Monitoring NSBB Therapy

• Clinical: Heart rate, blood pressure, symptom tolerance
• Target: HR 55-60 bpm or 25% reduction from baseline; SBP >90 mmHg
• HVPG monitoring (specialist centres): Target HVPG reduction >20% or to less than 12 mmHg
  • Predicts excellent protection from bleeding
  • Not routinely available outside research/expert centres

Managing Underlying Liver Disease

• Alcohol cessation: Abstinence essential
• Antiviral therapy: HBV (tenofovir, entecavir), HCV (direct-acting antivirals)
• NAFLD management: Weight loss, metabolic control
• Autoimmune hepatitis: Immunosuppression (prednisolone, azathioprine)
• Iron/copper removal: Venesection (haemochromatosis), chelation (Wilson's)
• Hepatocellular carcinoma surveillance: 6-monthly USS + AFP
• Vaccination: Hepatitis A, Hepatitis B, Pneumococcal, Influenza

---

8. Complications

Complications of Variceal Bleeding

Complications of Treatment

Endoscopic Variceal Ligation

• Post-banding ulceration and bleeding: 5-10% (usually self-limiting; may require repeat OGD)
• Dysphagia: Transient (resolves within days)
• Oesophageal stricture: Rare (less than 5%) with multiple banding sessions
• Perforation: Very rare (less than 1%)

Sclerotherapy

• Ulceration: 10-20%
• Stricture: 5-10%
• Mediastinitis: Rare but serious
• Pleural effusion: 10-15%
• Perforation: 1-2%

TIPSS

• Hepatic encephalopathy: 20-30% (manage with lactulose, rifaximin; may require shunt reduction)
• Stent stenosis/thrombosis: 20-30% with bare stents, less than 10% with covered stents (monitor with Doppler USS)
• Heart failure: Increased venous return may decompensate marginal cardiac function
• Haemolysis: Shear stress on RBCs
• Infection: Rare

Balloon Tamponade

• Aspiration pneumonia: 30-40% (intubation essential)
• Oesophageal ulceration: Common with prolonged inflation
• Oesophageal perforation: 5-10% (life-threatening)
• Pressure necrosis: Risk increases with duration (limit to 24 hours)

---

9. Prognosis and Outcomes

Mortality

Mortality by Child-Pugh Class:

• Child-Pugh A: 6-week mortality 0-5%
• Child-Pugh B: 6-week mortality 10-15%
• Child-Pugh C: 6-week mortality 20-35%

Predictors of Treatment Failure and Mortality

Clinical:

• Child-Pugh score ≥10
• Active bleeding at endoscopy (spurting)
• Large volume haematemesis (>2 units transfused in first 24 hours)
• Hepatocellular carcinoma
• Portal vein thrombosis
• Hepatorenal syndrome or acute kidney injury
• Hepatic encephalopathy Grade ≥2

Laboratory:

• HVPG >20 mmHg [14]
• Serum creatinine >150 μmol/L
• Serum bilirubin >100 μmol/L
• INR >2.0
• Serum sodium less than 130 mmol/L

Endoscopic:

• Active spurting variceal bleeding (F2)
• Gastric varices (higher rebleeding, harder to treat)

Rebleeding Risk

Factors Increasing Rebleeding Risk:

• Poor adherence to NSBB
• Ongoing alcohol consumption
• Large varices at index bleed
• Child-Pugh C cirrhosis
• Failure to achieve HVPG reduction >20%

Long-Term Outcomes

Survival:

• With abstinence (alcohol-related cirrhosis): 5-year survival 60-70%
• Continued alcohol use: 5-year survival 20-30%
• HCV cure (post-DAA): Improved survival, may see regression of varices in some
• Liver transplant: 5-year survival 70-80% post-transplant

Varix Regression:

• Rare without treatment of underlying cause
• May occur with viral cure (HCV), alcohol abstinence
• TIPSS reduces variceal size but does not eliminate need for surveillance

Liver Transplantation:

• Variceal bleeding is an indication for transplant assessment
• MELD score prioritises allocation
• Post-transplant, varices regress (portal hypertension resolves)

---

10. Evidence and Guidelines

Baveno VII Consensus (2022) [1]

Landmark international consensus on portal hypertension. Key recommendations [1,21,23]:

Primary Prophylaxis

• Screen all cirrhotic patients with OGD at diagnosis
• Non-invasive criteria: LSM less than 20 kPa + Platelets >150 → Low risk, can avoid OGD
• Small varices: Surveillance OGD 1-2 years; consider NSBB if high-risk (Child C, red signs)
• Medium/Large varices: NSBB (carvedilol preferred) OR EVL
• Do NOT combine NSBB + EVL for primary prophylaxis (no benefit, more adverse events)

Acute Bleeding

• Vasoactive drugs (terlipressin or octreotide/somatostatin) started immediately, before OGD
• Antibiotics (ceftriaxone 1g IV OD for 7 days) in all patients
• Emergency OGD within 12 hours
• EVL first-line endoscopic therapy
• Restrictive transfusion: Target Hb 7-8 g/dL
• Early TIPSS: Consider in Child-Pugh C (10-13) or Child-Pugh B with active bleeding at OGD

Secondary Prophylaxis

• Combination: NSBB + EVL (superior to either alone)
• TIPSS: For rebleeding despite optimal therapy

European Society of Gastrointestinal Endoscopy (ESGE) Guidelines (2022) [8]

• Emergency OGD within 12 hours for suspected variceal bleeding [8,22,28]
• EVL preferred over sclerotherapy
• Cyanoacrylate injection for gastric varices
• TIPSS for refractory bleeding

British Society of Gastroenterology (BSG) Guidelines [28]

• Align with Baveno VII and ESGE
• Emphasise multidisciplinary team approach (gastroenterology, hepatology, interventional radiology, surgery)

EASL Clinical Practice Guidelines (2024) [33]

• Updated guidance on portal hypertension management
• Integration of non-invasive assessment tools
• Risk stratification and personalised therapy approach

AASLD Practice Guidance (2024) [21]

• Comprehensive risk stratification framework
• Updated management algorithms for acute and chronic portal hypertension
• Evidence-based recommendations for decompensation prevention

NICE Guideline NG141: Acute Upper Gastrointestinal Bleeding (2016)

• Risk stratification with Glasgow-Blatchford Score
• OGD within 24 hours for most upper GI bleeding; within 12 hours for varices
• Restrictive transfusion strategy: Target Hb 7-8 g/dL

---

11. Special Populations

Acute-on-Chronic Liver Failure (ACLF)

Variceal bleeding can precipitate ACLF [21,26]:

• Definition: Acute deterioration in liver function + organ failure in cirrhosis
• Mortality: 30-50% at 28 days
• Management: Aggressive supportive care, treat precipitants, urgent transplant assessment

Portal Vein Thrombosis (PVT)

Non-cirrhotic portal hypertension due to PVT:

• Causes: Hypercoagulable states, malignancy, inflammation (pancreatitis, IBD), cirrhosis
• Varices: Often severe despite preserved liver function
• Management: Anticoagulation (if acute), NSBB/EVL for varices, TIPSS if refractory (may be technically challenging)

Splenic Vein Thrombosis

• Isolated gastric varices (IGV1) without oesophageal varices
• Cause: Pancreatitis, pancreatic cancer
• Management: Splenectomy curative (removes variceal blood supply)

Pregnancy

Rare but high-risk:

• Increased cardiac output → increased portal pressure → variceal bleeding risk
• Management: Multidisciplinary (hepatology, obstetrics)
  • NSBB safe in pregnancy
  • EVL if needed
  • Aim for vaginal delivery (C-section increases portal pressure)
  • TIPSS reserved for refractory cases

Paediatrics

• Causes: Biliary atresia, congenital hepatic fibrosis, portal vein thrombosis
• Management: Similar principles; EVL preferred; beta-blockers dose-adjusted
• Transplant: Consider early in children with decompensated cirrhosis

---

12. Patient and Layperson Explanation

What Are Oesophageal Varices?

Oesophageal varices are swollen, enlarged veins in the lower part of your food pipe (oesophagus). They develop when the blood flow through your liver is blocked, usually due to liver scarring (cirrhosis). This blockage increases pressure in the veins around the liver, forcing blood to find alternative routes back to your heart. Some of this blood travels through veins in your oesophagus, causing them to swell.

Why Are They Dangerous?

These swollen veins have thin walls and are under high pressure. This makes them fragile and prone to bursting and bleeding. When they bleed, it can be life-threatening because:

• The bleeding is often sudden and heavy
• It can cause severe blood loss quickly
• People with liver disease already have problems with blood clotting

What Are the Warning Signs of Bleeding?

Call 999 immediately if you experience:

• Vomiting blood (bright red or dark like coffee grounds)
• Black, tarry stools (digested blood)
• Feeling faint, dizzy, or confused
• Rapid heartbeat or breathlessness

How Are Varices Diagnosed?

Your doctor will perform a gastroscopy (endoscopy)—a test where a thin, flexible camera is passed down your throat to examine your oesophagus and stomach. This test can:

• Confirm if you have varices
• Check their size
• Treat them if needed

How Are They Treated?

If You Have Varices But Haven't Bled (Prevention)

1. Medications (Beta-blockers): Pills like propranolol or carvedilol reduce the pressure in the varices to prevent bleeding
2. Banding: During a gastroscopy, your doctor can place tiny elastic bands around the varices to shrink them

If Bleeding Occurs (Emergency Treatment)

1. Resuscitation: IV fluids and blood transfusions
2. Medications: Drugs to reduce pressure in the varices (terlipressin) and antibiotics to prevent infection
3. Emergency Gastroscopy: Banding or other treatments to stop the bleeding
4. Advanced Procedures: If bleeding doesn't stop, you may need a procedure called TIPSS (a tube placed inside your liver to reduce pressure)

Can Varices Be Cured?

Varices cannot be permanently "cured" unless the underlying liver disease is treated. However:

• Medications and banding can reduce the risk of bleeding
• Treating the liver disease (e.g., stopping alcohol, treating hepatitis) may prevent varices from getting worse
• In severe cases, a liver transplant may be the only cure

What Can You Do to Reduce Your Risk?

• Stop drinking alcohol if you have liver disease
• Take your medications exactly as prescribed
• Attend regular check-ups and gastroscopies
• Avoid NSAIDs (like ibuprofen) which can increase bleeding risk
• Seek immediate help if you have any warning signs of bleeding

Living with Varices

Many people with varices live for years without bleeding by:

• Following medical advice
• Taking preventive medications
• Having regular monitoring
• Managing their liver disease

Your healthcare team is here to support you. Don't hesitate to ask questions or report any concerning symptoms.

---

13. Examination Focus (MRCP / MRCS / Finals)

High-Yield Exam Topics

Viva/OSCE Stations

Station 1: Acute Variceal Bleeding Management

• Scenario: 55-year-old with known alcoholic cirrhosis presents with massive haematemesis and hypotension
• Expected Answer:
  1. Resuscitation: ABCDE, large bore IV access, fluid resuscitation (avoid over-resuscitation, target SBP 90-100), crossmatch
  2. Pharmacotherapy: Terlipressin 2mg IV stat (or octreotide), Ceftriaxone 1g IV
  3. Emergency OGD within 12 hours for EVL
  4. Restrictive transfusion: Target Hb 7-8 g/dL
  5. Secondary prophylaxis: NSBB + repeat EVL after stabilisation
• Mark Scheme: Immediate vasoactive drugs (3 points), antibiotics (2 points), emergency endoscopy (3 points), restrictive transfusion (1 point), secondary prophylaxis (1 point)

Station 2: Primary Prophylaxis Discussion

• Scenario: Screening OGD shows large oesophageal varices in compensated cirrhotic. What do you do?
• Expected Answer:
  • Primary prophylaxis indicated
  • "Options: NSBB (carvedilol or propranolol) OR EVL"
  • "Preferred: Carvedilol (Baveno VII) due to superior HVPG reduction"
  • Do NOT combine NSBB + EVL for primary prophylaxis
  • Surveillance OGD as per guidelines

Station 3: Interpretation of Endoscopy Report

• Given: OGD report describing "Grade 3 varices with red wale marks"
• Expected Answer:
  • Large varices (>10mm, >33% lumen)
  • Red wale marks = high-risk stigmata (thin wall, high pressure)
  • High bleeding risk (~15% per year)
  • Primary prophylaxis essential (NSBB or EVL)

Written Exam (MCQ/SBA) High-Yield Questions

Q1: A 52-year-old with hepatitis C cirrhosis presents with haematemesis. OGD shows actively bleeding oesophageal varices. After successful EVL, what is the MOST important additional therapy to reduce mortality? A) Proton pump inhibitor B) Tranexamic acid C) Antibiotic prophylaxis ✓ D) Fresh frozen plasma E) Octreotide infusion

Answer: C - Antibiotic prophylaxis (ceftriaxone) reduces infections by 35% and mortality by 9% [13]

Q2: What is the target haemoglobin in acute variceal bleeding? A) 10-12 g/dL B) 9-10 g/dL C) 7-8 g/dL ✓ D) 6-7 g/dL E) 12-14 g/dL

Answer: C - Restrictive transfusion strategy (Hb 7-8) reduces rebleeding and mortality vs liberal [15]

Q3: A 60-year-old with Child-Pugh C cirrhosis (score 12) has a first episode of variceal bleeding. OGD shows active bleeding at endoscopy despite EVL. According to Baveno VII, what is the next step? A) Repeat EVL in 2 weeks B) Increase terlipressin dose C) Early TIPSS within 72 hours ✓ D) Sengstaken-Blakemore tube E) Liver transplant assessment

Answer: C - Early TIPSS indicated in Child-Pugh C (10-13) with active bleeding at OGD [12]

Q4: Which NSBB is preferred for primary prophylaxis of variceal bleeding per Baveno VII? A) Propranolol B) Carvedilol ✓ C) Atenolol D) Bisoprolol E) Nadolol

Answer: B - Carvedilol (additional alpha-1 blockade, superior HVPG reduction) [1,7]

Q5: At what HVPG does variceal bleeding risk begin? A) >6 mmHg B) >10 mmHg C) >12 mmHg ✓ D) >16 mmHg E) >20 mmHg

Answer: C - HVPG >12 mmHg = bleeding risk; >20 mmHg = high mortality [14]

Exam Pearls and Mnemonics

"BLAST" for Acute Variceal Bleeding:

• Blood products (restrictive: Hb 7-8)
• Ligation (EVL within 12 hours)
• Antibiotics (ceftriaxone 1g IV)
• Splanchnic vasoconstrictor (terlipressin)
• TIPSS (if refractory or high-risk)

HVPG Thresholds:

• 10: Varices develop
• 12: Varices bleed
• 20: High mortality

"3 C's" of Primary Prophylaxis:

• Carvedilol (preferred NSBB)
• Combination NOT for primary (only secondary)
• Children and compensated cirrhosis get screened

Child-Pugh Mnemonic: "ABCDE" but only 5 variables:

• Ascites
• Bilirubin
• Coagulation (INR)
• Don't forget (Albumin)
• Encephalopathy

Common Exam Mistakes

❌ Giving NSBB + EVL for primary prophylaxis (no benefit, more adverse events) [1] ✅ Either NSBB OR EVL

❌ Transfusing to Hb >9 g/dL (increases portal pressure and rebleeding) [15] ✅ Target Hb 7-8 g/dL

❌ Forgetting antibiotics in acute bleed ✅ Ceftriaxone 1g IV OD for 7 days ALWAYS [13]

❌ Delaying endoscopy beyond 12 hours ✅ Emergency OGD within 12 hours [8]

❌ Using atenolol or bisoprolol (cardioselective, don't reduce portal pressure) ✅ NON-selective beta-blockers only (propranolol, carvedilol, nadolol)

---

14. References

Primary Sources

1. de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959-974. PMID: 35120736. DOI: 10.1016/j.jhep.2021.12.022

2. Jothimani D, Cramp ME, Mitchell JD. Liver Cirrhosis and Portal Hypertension: How to Deal with Esophageal Varices? Med Clin North Am. 2023;107(3):525-540. PMID: 37001949. DOI: 10.1016/j.mcna.2023.01.005

3. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46(3):922-938. PMID: 17879356. DOI: 10.1002/hep.21907

4. Groszmann RJ, Garcia-Tsao G, Bosch J, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med. 2005;353(21):2254-2261. PMID: 16306522. DOI: 10.1056/NEJMoa044456

5. Singh S, Mukherjee S, Nautiyal A, Kale S, Rai P. Comprehensive approach to esophageal variceal bleeding: From prevention to treatment. World J Gastroenterol. 2024;30(43):4612-4633. PMID: 39575399. DOI: 10.3748/wjg.v30.i43.4612

6. Bernard B, Lebrec D, Mathurin P, Opolon P, Poynard T. Beta-adrenergic antagonists in the prevention of gastrointestinal rebleeding in patients with cirrhosis: a meta-analysis. Hepatology. 1997;25(1):63-70. PMID: 8985267. DOI: 10.1002/hep.510250113

7. Turco L, Villanueva C, La Mura V, García-Pagán JC, Reiberger T, Genescà J. Carvedilol as the new non-selective beta-blocker of choice in patients with cirrhosis and portal hypertension. Liver Int. 2023;43(6):1180-1191. PMID: 36897563. DOI: 10.1111/liv.15566

8. Gralnek IM, Camus Duboc M, Garcia-Pagan JC, et al. Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2022;54(11):1094-1120. PMID: 36174643. DOI: 10.1055/a-1939-6774

9. Huaringa-Marcelo J, Cárdenas-Crespo G, Ticse-Aguirre R. Vasoactive Agents for the Management of Acute Variceal Bleeding: A Systematic Review and Meta-analysis. J Gastrointestin Liver Dis. 2021;30(1):105-114. PMID: 33723542. DOI: 10.15403/jgld-3206

10. Lo GH, Chen WC, Chen MH, et al. Endoscopic ligation vs. nadolol in the prevention of first variceal bleeding in patients with cirrhosis. Gastrointest Endosc. 2004;59(3):333-338. PMID: 14997127.

11. Ahmed O, Patel S, Ginsburg M, Weinstein JL, Khaja MS. Transjugular Intrahepatic Portosystemic Shunt Placement: Entering the Era of Controlled Expansion. Cardiovasc Intervent Radiol. 2023;46(6):663-673. PMID: 37138106. DOI: 10.1007/s00270-023-03458-2

12. García-Pagán JC, Caca K, Bureau C, et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med. 2010;362(25):2370-2379. PMID: 20538000. DOI: 10.1056/NEJMoa0910102

13. 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. PMID: 17030175. DOI: 10.1053/j.gastro.2006.07.010

14. Abraldes JG, Bureau C, Stefanescu H, Augustin S. Update in the Treatment of the Complications of Cirrhosis. Clin Gastroenterol Hepatol. 2023;21(8):1955-1969. PMID: 36972759. DOI: 10.1016/j.cgh.2023.03.006

15. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368(1):11-21. PMID: 23281973. DOI: 10.1056/NEJMoa1211801

16. North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. N Engl J Med. 1988;319(15):983-989. PMID: 3262200.

17. Iwakiri Y, Shah V, Rockey DC. Vascular pathobiology in chronic liver disease and cirrhosis - current status and future directions. J Hepatol. 2014;61(4):912-924. PMID: 24911462. DOI: 10.1016/j.jhep.2014.05.047

18. Jhajharia A, Bapaye A, Gadhikar H, et al. Endoscopic ultrasonography-guided coil embolization and cyanoacrylate injection versus cyanoacrylate injection alone for gastric varices: randomized controlled trial. Endoscopy. 2025;57(2):85-95. PMID: 39293480. DOI: 10.1055/a-2396-8435

19. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60(8):646-649. PMID: 4541913.

20. Oakland K, Kahan BC, Chauhan A, Jairath V. Risk stratification in upper and lower GI bleeding: Which scores should we use? Best Pract Res Clin Gastroenterol. 2019;42-43:101608. PMID: 31785738. DOI: 10.1016/j.bpg.2019.04.006

21. Kaplan DE, Ripoll C, Thiele M, et al. AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis. Hepatology. 2024;79(5):1180-1211. PMID: 37870298. DOI: 10.1097/HEP.0000000000000647

22. Singh S, Mukherjee S, Nautiyal A, Kale S, Rai P. Comprehensive approach to esophageal variceal bleeding: From prevention to treatment. World J Gastroenterol. 2024;30(43):4612-4633. PMID: 39575399. DOI: 10.3748/wjg.v30.i43.4612

23. Jakab SS, Garcia-Tsao G. Screening and Surveillance of Varices in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2019;17(1):26-29. PMID: 29551741. DOI: 10.1016/j.cgh.2018.03.012

24. Abuelazm MT, Cheema HA, Jafar U, et al. Transjugular intrahepatic portosystemic shunt with or without variceal embolization to prevent variceal rebleeding: an updated meta-analysis. Expert Rev Gastroenterol Hepatol. 2023;17(7):741-751. PMID: 37306478. DOI: 10.1080/17474124.2023.2223974

25. Bai Y, Liu J, Wu W, et al. Transjugular intrahepatic portosystemic shunt (TIPS) with variceal embolization reduces rebleeding risk for patients with portal pressure gradient over 12 mmHg: A long-term follow-up study. Eur J Radiol. 2024;181:111740. PMID: 39288645. DOI: 10.1016/j.ejrad.2024.111740

26. Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(1014-1048). PMID: 34161722. DOI: 10.1002/hep.31884

27. Sarin SK, Lahoti D, Saxena SP, et al. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. Hepatology. 1992;16(6):1343-1349. PMID: 1446890. DOI: 10.1002/hep.1840160607

28. Tripathi D, Stanley AJ, Hayes PC, et al. UK guidelines on the management of variceal haemorrhage in cirrhotic patients. Gut. 2015;64(11):1680-1704. PMID: 25887380. DOI: 10.1136/gutjnl-2015-309262

29. Reiberger T, Ulbrich G, Ferlitsch A, et al. Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol. Gut. 2013;62(11):1634-1641. PMID: 23250049. DOI: 10.1136/gutjnl-2012-304038

30. Pang JXQ, Ross A, Lim G, et al. Variceal screening interval: a systematic review and meta-analysis of varices in compensated cirrhosis. Hepatology. 2022;76(5):1382-1394. PMID: 35437811. DOI: 10.1002/hep.32515

31. Lv Y, Yang Z, Liu L, et al. Early TIPS with covered stents versus standard treatment for acute variceal bleeding in patients with advanced cirrhosis: a randomised controlled trial. Lancet Gastroenterol Hepatol. 2019;4(8):587-598. PMID: 31253547. DOI: 10.1016/S2468-1253(19)30090-1

32. Laleman W, Simon-Talero M, Maleux G, et al. Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: a multicenter survey on safety and efficacy. Hepatology. 2013;57(6):2448-2457. PMID: 23300059. DOI: 10.1002/hep.26314

33. Thiele M, Albillos A, Abraldes JG, et al. EASL Clinical Practice Guidelines on the management of portal hypertension. J Hepatol. 2024;80(2):371-406. PMID: 37989497. DOI: 10.1016/j.jhep.2023.11.003

---

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances and local guidelines. Always consult appropriate specialists for management of acute variceal bleeding and portal hypertension. This content does not replace clinical judgment or specialist consultation.

---

Document Information:

• Version: 4.0 (Gold Standard Enhanced)
• Last Updated: 2026-01-16
• Evidence Base: Baveno VII (2022), ESGE (2022), AASLD (2024), EASL (2024), 33 PubMed-indexed citations
• Word Count: ~14,200 words
• Line Count: 1,509 lines
• Citation Count: 33
• Target Audience: MRCP, MRCS, FRCS, Emergency Medicine, Medical Students
• Anki Cards: 52 cards generated across 7 decks